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  1. Dosage de la 25 OH vitamine D: expérience du laboratoire central de biochimie clinique du Centre Hospitalier Ibn Sina

    PubMed Central

    Handor, Najat; Elalami, Sanae; Bouabdellah, Mounya; Srifi, Abdelatif; Esselmani, Hicham; Benchekroun, Laila; Chabraoui, Layachi

    2014-01-01

    La connaissance de la physiologie de la vitamine D a considérablement progressé ces dernières années, la faisant passer de simple vitamine à tropisme purement phosphocalcique et osseux à celui d'hormone jouant un rôle crucial dans de nombreux mécanismes physiologiques et dont le déficit est impliqué dans plusieurs pathologies. Nous présentons, dans ce travail, l'expérience du laboratoire central de biochimie dans le dosage de la 25 OH vitamine D. Enquête descriptive exhaustive portant sur les dosages de la 25 OH vitamine D effectués chez 350 patients du Centre Hospitalier Ibn Sina (CHIS). La méthode adoptée est un dosage immunologique par chimiluminescence sur microparticules réalisés sur l'auto-analyseur ARCHITECT 8200 (ABBOTT®) pendant une période de six mois (du 01 Juin 2011 au 31 Decembre 2011). Quatre vingt et onze pourcent des patients présentent une hypovitaminose. En effet 76,6% des patients souffrent d'une insuffisance en vitamine D, 12,3% de carence vitaminique et 2,6% d'ostéomalacie. L'hypovitaminose est associée dans 92,18% des cas à une normocalcémie, dans 76,87% des cas à une Hyperparathormone, dans 92,81% à des troubles thyroïdiens et dans 97,5% à une insuffisance rénale. Par ailleurs aucune relation statistiquement significative n'est établie entre l'hypovitaminose et le diabète. A la lumière des implications des hypovitaminoses dans plusieurs pathologies ou dans leurs complications et au vu du nombre élevé de patients présentant un déficit en vitamine D, il paraît judicieux d'envisager une étude épidémiologique sur le statut en vitamine D dans la population marocaine comme outil préventif avant d'élargir le dosage de ce marqueur biologique en vue d'une éventuelle supplémentation. PMID:25374649

  2. L'intérêt du dosage de la calcémie devant une tumeur maxillaire: découverte d'une hyperparathyroïdie primitive

    PubMed Central

    Esselmani, Hicham; Bouabdellah, Mounya; Benchekroun, Laila; Elalami, Sanae; Handor, Najat; Chabraoui, Layachi

    2014-01-01

    L'hyperparathyroïdie primaire (HPP) est une affection fréquente, aujourd'hui découverte fortuitement dans 75 à 80% des cas par un dosage systématique de la calcémie biologique. Le diagnostic de cette affection se base sur la mise en évidence concomitante d'une calcémie élevée, d'un taux de parathormone (PTH) élevé (80% des cas) ou normal (20% des cas), et d'une calciurie supérieure à 150 mg/24 heures. Les manifestations squelettiques graves (ostéite fibrokystique, tumeurs brunes, fractures pathologiques) sont rares de nos jours. Les tumeurs brunes constituent un mode de révélation rare de l'hyperparathyroïdie primaire et leur localisation au niveau des maxillaires est exceptionnelle. Nous rapportons ici la longue histoire de la maladie d'un homme de 42 ans atteint d'une hyperparathyroïdie primitive découverte devant une tuméfaction jugale, une hypercalcémie majeure à 3.92 mmol/l et une tumeur brune maxillaire et nous soulignant le rôle du bilan biologique raisonné et de son interprétation en tant que révélateur diagnostique pour orienter le clinicien vers l'hyperparathyroïdie primaire. PMID:25469208

  3. [Understanding dosage calculations].

    PubMed

    Benlahouès, Daniel

    2016-01-01

    The calculation of dosages in paediatrics is the concern of the whole medical and paramedical team. This activity must generate a minimum of risks in order to prevent care-related adverse events. In this context, the calculation of dosages is a practice which must be understood by everyone.

  4. Microbicide dosage forms.

    PubMed

    Rohan, L C; Devlin, B; Yang, H

    2014-01-01

    Microbicides are topically applied, user controlled dosage forms that are being developed to prevent the transmission of HIV during coitus. Early candidates focused on coitally dependent dosage forms such as gels and creams. More recent development has focused on broadening the coitally dependent options through the introduction of films and fast dissolving tablets. Additionally, it has become important to have longer acting products to minimize the burden of user compliance and thus vaginal rings have been developed providing sustained delivery of antiretroviral drugs. This chapter discusses the history of microbicides along with a detailed description of coitally dependent products, gels, films, tablets diaphragms, as well as coitally independent dosage forms such as vaginal rings and the introduction of a new technology, electrospun fibers.

  5. Evolution of dosage compensation.

    PubMed

    Steinemann, M; Steinemann, S; Turner, B M

    1996-04-01

    In polytene chromosome squashes from the fruit fly Drosophila melanogaster, the single, dosage-compensated X chromosome in males can be distinguished from the autosomes by the presence of an isoform of histone H4 acetylated at lysine 16, H4.Ac16. We have used H4.Ac16 as a marker to examine the evolving relationship between dosage compensation and sex chromosome composition in species of Drosophila with one (D. melanogaster), two (D. pseudoobscura) or three (D. miranda) identifiable X chromosome arms. In each case, we find that H4.Ac16 is distributed as discrete, closely spaced bands along the entire length of each X chromosome, the only exception being the X2 chromosome of D. miranda in which a terminal region constituting about 10% of the chromosome by length is not labelled with anti-H4.Ac16 antibodies. We conclude that, with this exception, dosage compensation extends along the X chromosomes of all three species. As D. pseudoobscura and D. miranda diverged only about 2 Mya, the spread of dosage-compensated loci along X2 has been rapid, suggesting that regional changes rather than piecemeal, gene-by-gene, changes may have been involved.

  6. Dosage Compensation in Mammals

    PubMed Central

    Brockdorff, Neil; Turner, Bryan M.

    2015-01-01

    Many organisms show major chromosomal differences between sexes. In mammals, females have two copies of a large, gene-rich chromosome, the X, whereas males have one X and a small, gene-poor Y. The imbalance in expression of several hundred genes is lethal if not dealt with by dosage compensation. The male–female difference is addressed by silencing of genes on one female X early in development. However, both males and females now have only one active X chromosome. This is compensated by twofold up-regulation of genes on the active X. This complex system continues to provide important insights into mechanisms of epigenetic regulation. PMID:25731764

  7. Controlled release liquid dosage formulation

    DOEpatents

    Benton, Ben F.; Gardner, David L.

    1989-01-01

    A liquid dual coated dosage formulation sustained release pharmaceutic having substantial shelf life prior to ingestion is disclosed. A dual coating is applied over controlled release cores to form dosage forms and the coatings comprise fats melting at less than approximately 101.degree. F. overcoated with cellulose acetate phthalate or zein. The dual coated dosage forms are dispersed in a sugar based acidic liquid carrier such as high fructose corn syrup and display a shelf life of up to approximately at least 45 days while still retaining their release profiles following ingestion. Cellulose acetate phthalate coated dosage form cores can in addition be dispersed in aqueous liquids of pH <5.

  8. Nuclear organization and dosage compensation.

    PubMed

    Chow, Jennifer C; Heard, Edith

    2010-11-01

    Dosage compensation is a strategy to deal with the imbalance of sex chromosomal gene products relative to autosomes and also between the sexes. The mechanisms that ensure dosage compensation for X-chromosome activity have been extensively studied in mammals, worms, and flies. Although each entails very different mechanisms to equalize the dose of X-linked genes between the sexes, they all involve the co-ordinate regulation of hundreds of genes specifically on the sex chromosomes and not the autosomes. In addition to chromatin modifications and changes in higher order chromatin structure, nuclear organization is emerging as an important component of these chromosome-wide processes and in the specific targeting of dosage compensation complexes to the sex chromosomes. Preferential localization within the nucleus and 3D organization are thought to contribute to the differential treatment of two identical homologs within the same nucleus, as well as to the chromosome-wide spread and stable maintenance of heterochromatin.

  9. Radiopharmaceutical dosage selection for pediatric nuclear medicine

    SciTech Connect

    Shore, R.M.; Hendee, W.R.

    1986-02-01

    To identify the most rational method for adjusting adult radiopharmaceutical dosages for children, four methods of dosage computation were examined from the perspectives of diagnostic adequacy and radiation absorbed dose. For static imaging, information density is the most important factor in study quality, and adjustment of dosage by body weight (Wt) for thick organs, and body surface area (BSA) for thin organs is recommended. Compared with adults, small children receive less radiation exposure if radiopharmaceutical dosages are adjusted by Wt, and slightly greater exposure if dosages are adjusted by BSA. For dynamic imaging studies, dosage requirements are governed by the spatial resolution needed for region of interest assignment, and the statistical reliability of the time-activity data. For dynamic renal imaging, renograms of similar quality are obtained if dosages are adjusted by height (Ht). Dynamic cardiac studies might appear to require dosages even larger than those adjusted by Ht which would result in higher radiation absorbed doses to pediatric patients. However, smaller dosages can be used in children by prolonging the imaging time and accepting lower temporal resolution. Dosage requirements for dynamic studies depend on which physiologic characteristics are measured from the time-activity data. Since the measurements of some characteristics demand higher count rates than others, dosage requirements ultimately depend on which measurements are clinically necessary. Close attention to the factors that determine these requirements may yield significant reduction in dosages, and thus in radiation exposure, for patients of all ages.

  10. The Enigma of Rapamycin Dosage.

    PubMed

    Mukhopadhyay, Suman; Frias, Maria A; Chatterjee, Amrita; Yellen, Paige; Foster, David A

    2016-03-01

    The mTOR pathway is a critical regulator of cell growth, proliferation, metabolism, and survival. Dysregulation of mTOR signaling has been observed in most cancers and, thus, the mTOR pathway has been extensively studied for therapeutic intervention. Rapamycin is a natural product that inhibits mTOR with high specificity. However, its efficacy varies by dose in several contexts. First, different doses of rapamycin are needed to suppress mTOR in different cell lines; second, different doses of rapamycin are needed to suppress the phosphorylation of different mTOR substrates; and third, there is a differential sensitivity of the two mTOR complexes mTORC1 and mTORC2 to rapamycin. Intriguingly, the enigmatic properties of rapamycin dosage can be explained in large part by the competition between rapamycin and phosphatidic acid (PA) for mTOR. Rapamycin and PA have opposite effects on mTOR whereby rapamycin destabilizes and PA stabilizes both mTOR complexes. In this review, we discuss the properties of rapamycin dosage in the context of anticancer therapeutics.

  11. [Dosage forms of phytogenic drugs].

    PubMed

    Luftensteiner, C P; Viernstein, H

    1999-01-01

    Herbal drug formulation is a challenge in pharmaceutical technology due to the complex physicochemical properties of these multicomponent materials. Potential instabilities of the pharmacologically active and coactive substances as well as incompatibilities and interactions of the extracted compounds and excipients have to be considered. Microbial contamination of the applied plant material might limit the shelf life of the products. Using state of the art methods in formulation stable preparations are obtained; additionally compliance of drugs might be enhanced due to simplified application or better sensorial quality. Nowadays, besides traditional pharmacopoeial aqueous, ethanolic, or (partially) dried extracts fluid, semisolid, or solid dosage forms of these extracts are in use, for example syrups, juices, drops, liniments, gels, ointments, creams, suppositories, tablets, coated tablets (dragees) as well as soft and hard gelatine capsules.

  12. Dosage Compensation of the Sex Chromosomes

    PubMed Central

    Disteche, Christine M.

    2013-01-01

    Differentiated sex chromosomes evolved because of suppressed recombination once sex became genetically controlled. In XX/XY and ZZ/ZW systems, the heterogametic sex became partially aneuploid after degeneration of the Y or W. Often, aneuploidy causes abnormal levels of gene expression throughout the entire genome. Dosage compensation mechanisms evolved to restore balanced expression of the genome. These mechanisms include upregulation of the heterogametic chromosome as well as repression in the homogametic sex. Remarkably, strategies for dosage compensation differ between species. In organisms where more is known about molecular mechanisms of dosage compensation, specific protein complexes containing noncoding RNAs are targeted to the X chromosome. In addition, the dosage-regulated chromosome often occupies a specific nuclear compartment. Some genes escape dosage compensation, potentially resulting in sex-specific differences in gene expression. This review focuses on dosage compensation in mammals, with comparisons to fruit flies, nematodes, and birds. PMID:22974302

  13. Mechanisms of X Chromosome Dosage Compensation

    PubMed Central

    Ercan, Sevinç

    2015-01-01

    In many animals, males have one X and females have two X chromosomes. The difference in X chromosome dosage between the two sexes is compensated by mechanisms that regulate X chromosome transcription. Recent advances in genomic techniques have provided new insights into the molecular mechanisms of X chromosome dosage compensation. In this review, I summarize our current understanding of dosage imbalance in general, and then review the molecular mechanisms of X chromosome dosage compensation with an emphasis on the parallels and differences between the three well-studied model systems, M. musculus, D. melanogaster and C. elegans. PMID:25628761

  14. "Cirque du Freak."

    ERIC Educational Resources Information Center

    Rivett, Miriam

    2002-01-01

    Considers the marketing strategies that underpin the success of the "Cirque du Freak" series. Describes how "Cirque du Freak" is an account of events in the life of schoolboy Darren Shan. Notes that it is another reworking of the vampire narrative, a sub-genre of horror writing that has proved highly popular with both adult and…

  15. [Pharmaceutical advice concerning different pharmaceutical dosage forms].

    PubMed

    Szakonyi, Gergely; Zelkó, Romána

    2010-01-01

    The present paper summarizes the commonly applied types of drug uptake and the pharmacists' advice concerning a certain dosage form. The manuscript also deals with the modified release dosage forms and their abbreviations in the name of the marketing authorized products.

  16. Physicochemical interactions in solid dosage forms.

    PubMed

    Narang, Ajit S; Desai, Divyakant; Badawy, Sherif

    2012-10-01

    Complete characterization and mechanistic understanding of physicochemical interactions in solid dosage forms are not only important for consistent manufacturability, stability, and bioavailability of the drug product, but are also expected under the quality-by-design paradigm of drug development. Lack of this understanding can impact successful and timely development, scale-up, and commercial manufacture of dosage forms. This article highlights the stability and bioavailability implications of physicochemical interactions in dosage forms citing a couple of examples where such interactions necessitated the recall of commercial drug products.

  17. 21 CFR 526.464 - Cloxacillin intramammary dosage forms.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Cloxacillin intramammary dosage forms. 526.464... (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS INTRAMAMMARY DOSAGE FORMS § 526.464 Cloxacillin intramammary dosage forms....

  18. La naissance du parsec

    NASA Astrophysics Data System (ADS)

    Arenou, F.

    2010-01-01

    Les définitions du parsec et de la magnitude absolue sont le fruit de compromis pour régler trois problèmes entremêlés au début du XXème siècle: quelle unité de distance stellaire adopter? Quel nom lui donner? Comment comparer les luminosités intrinsèques des différentes étoiles?

  19. [Dosage compensation mechanism of X chromosome].

    PubMed

    Wang, Yan-Yun; Chen, Mei; Li, Bin

    2012-08-01

    Dosage compensation mechanism is crucial for the balance expression of X chromosome genes, which ensures the protein or enzyme encoded by the X chromosome to be equal or almost equal expression amounts between males and females. However, different organisms have evolved distinct dosage compensation strategies, and so far three kinds of dosage compensation strategies among organisms have been reported. The first strategy is that the single male X chromosome expression is doubly activated; the second one is to inactivate one female X chromosome by leaving both sexes with one active allele; and the third one is to reduce the expression to half activity in both X chromosomes of the female. The study of dosage compensation will be useful to reveal the mechanism of regulation of X-linked genes as well as the evolution and the differentiation progress of the sex chromosome, and it can also contribute to illustrate mutation and distortion of sex chromosome. Therefore, this paper briefly reviewed and discussed the progresses and prospects of the important mechanism of dosage compensation.

  20. Active compounds release from semisolid dosage forms.

    PubMed

    Olejnik, Anna; Goscianska, Joanna; Nowak, Izabela

    2012-11-01

    The aim of this paper is to review all the aspects of the in vitro release testing (IVRT) from semisolid dosage forms. Although none of the official dissolution methods has been specified for use with semisolid dosage forms, their utility for assessing release rates of drugs from semisolid dosage forms has become a topic of considerable interest. One can expect to overcome such complexity in the future, when the official "Topical and Transdermal Drug Products-Product Performance Tests" will be published in an issue of the Pharmacopeial Forum. Many factors such as type of the dissolution medium, membrane, temperature, and speed have an influence on the mechanism and kinetics of the release testing from gels, creams, and ointments; therefore, those parameters have been widely discussed.

  1. Prescribing Errors Involving Medication Dosage Forms

    PubMed Central

    Lesar, Timothy S

    2002-01-01

    CONTEXT Prescribing errors involving medication dose formulations have been reported to occur frequently in hospitals. No systematic evaluations of the characteristics of errors related to medication dosage formulation have been performed. OBJECTIVE To quantify the characteristics, frequency, and potential adverse patient effects of prescribing errors involving medication dosage forms . DESIGN Evaluation of all detected medication prescribing errors involving or related to medication dosage forms in a 631-bed tertiary care teaching hospital. MAIN OUTCOME MEASURES Type, frequency, and potential for adverse effects of prescribing errors involving or related to medication dosage forms. RESULTS A total of 1,115 clinically significant prescribing errors involving medication dosage forms were detected during the 60-month study period. The annual number of detected errors increased throughout the study period. Detailed analysis of the 402 errors detected during the last 16 months of the study demonstrated the most common errors to be: failure to specify controlled release formulation (total of 280 cases; 69.7%) both when prescribing using the brand name (148 cases; 36.8%) and when prescribing using the generic name (132 cases; 32.8%); and prescribing controlled delivery formulations to be administered per tube (48 cases; 11.9%). The potential for adverse patient outcome was rated as potentially “fatal or severe” in 3 cases (0.7%), and “serious” in 49 cases (12.2%). Errors most commonly involved cardiovascular agents (208 cases; 51.7%). CONCLUSIONS Hospitalized patients are at risk for adverse outcomes due to prescribing errors related to inappropriate use of medication dosage forms. This information should be considered in the development of strategies to prevent adverse patient outcomes resulting from such errors. PMID:12213138

  2. Cri du chat syndrome

    MedlinePlus

    ... the infant's cry, which is high-pitched and sounds like a cat. Causes Cri du chat syndrome is rare. It is caused by a missing piece of chromosome 5. Most cases are believed to occur during the development of ... Cry that is high-pitched and may sound like a cat Downward slant to the eyes ...

  3. Enteric coating of mycophenolate reduces dosage adjustments.

    PubMed

    Brister, K; Yau, C L; Slakey, D

    2009-06-01

    Mycophenolate mofetil (MMF) and enteric-coated mycophenolate sodium (EC-MPS) are bioequivalent. However, the effectiveness of MMF may be limited by gastrointestinal (GI) side effects. This study assessed the relationship between the number of medication dosage adjustments and posttransplantation side effects. In a review of 109 kidney transplant patients, 65 initially received MMF and 44 initially received EC-MPS. The incidences of patient-reported GI complications were significantly different: MMF 45.5% vs EC-MPS 35.3% (P = .0194). The proportions of patients requiring dosage adjustment due to GI complications were MMF 5.9% and EC-MPS 2.3% (P < .0001). Patients receiving MMF were more likely to experience GI complications resulting in dosage adjustment (odds ratio = 9.9; P = .0306). The incidences of acute rejection, cytomegalovirus (CMV), and leukopenia resulting in dosage adjustment were not significantly different. Patients receiving MMF required more immunosuppressive medication adjustments, which may complicate care and decrease overall compliance.

  4. Traitement mathématique des resultats du dosage titrimétrique.

    PubMed

    Chernova, N A; Mel'nikov, P P; Komissarova, L N; Spytzin, V

    1971-06-01

    A statistical method is proposed for treatment of titrimetric results. It permits differentiation between true effects on titrimetric graphs and the effects that are the result of random scattering of the experimental points. As an example the mathematical treatment of the data for the system Sc(3+):H(2)PO(2)(-) is considered.

  5. Basics of compounding foam dosage forms.

    PubMed

    Allen, Loyd V

    2013-01-01

    The purpose of this article is to provide information on the use of foam dosage forms and pharmacists' ability to extemporaneously compound them. The article provides: (1) a discussion on the rationale and advantages of using foams, (2) a differentiation between the various types and structures of foams, (3) a list of the various types of ingredients and examples of each, and (4) a description of the preparation of pharmaceutical foams.

  6. Estimated Maximal Safe Dosages of Tumescent Lidocaine

    PubMed Central

    Jeske, Daniel R.

    2016-01-01

    BACKGROUND: Tumescent lidocaine anesthesia consists of subcutaneous injection of relatively large volumes (up to 4 L or more) of dilute lidocaine (≤1 g/L) and epinephrine (≤1 mg/L). Although tumescent lidocaine anesthesia is used for an increasing variety of surgical procedures, the maximum safe dosage is unknown. Our primary aim in this study was to measure serum lidocaine concentrations after subcutaneous administration of tumescent lidocaine with and without liposuction. Our hypotheses were that even with large doses (i.e., >30 mg/kg), serum lidocaine concentrations would be below levels associated with mild toxicity and that the concentration-time profile would be lower after liposuction than without liposuction. METHODS: Volunteers participated in 1 to 2 infiltration studies without liposuction and then one study with tumescent liposuction totally by local anesthesia. Serum lidocaine concentrations were measured at 0, 2, 4, 6, 8, 10, 12, 14, 16, 18, and 24 hours after each tumescent lidocaine infiltration. Area under the curve (AUC∞) of the serum lidocaine concentration-time profiles and peak serum lidocaine concentrations (Cmax) were determined with and without liposuction. For any given milligram per kilogram dosage, the probability that Cmax >6 μg/mL, the threshold for mild lidocaine toxicity was estimated using tolerance interval analysis. RESULTS: In 41 tumescent infiltration procedures among 14 volunteer subjects, tumescent lidocaine dosages ranged from 19.2 to 52 mg/kg. Measured serum lidocaine concentrations were all <6 μg/mL over the 24-hour study period. AUC∞s with liposuction were significantly less than those without liposuction (P = 0.001). The estimated risk of lidocaine toxicity without liposuction at a dose of 28 mg/kg and with liposuction at a dose of 45 mg/kg was ≤1 per 2000. CONCLUSIONS: Preliminary estimates for maximum safe dosages of tumescent lidocaine are 28 mg/kg without liposuction and 45 mg/kg with liposuction. As a

  7. 21 CFR 520.1044 - Gentamicin sulfate oral dosage forms.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Gentamicin sulfate oral dosage forms. 520.1044... (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.1044 Gentamicin sulfate oral dosage forms....

  8. 21 CFR 520.1120 - Haloxon oral dosage forms.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Haloxon oral dosage forms. 520.1120 Section 520...) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.1120 Haloxon oral dosage forms....

  9. 21 CFR 520.1720 - Phenylbutazone oral dosage forms.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Phenylbutazone oral dosage forms. 520.1720 Section... (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.1720 Phenylbutazone oral dosage forms....

  10. 21 CFR 520.903 - Febantel oral dosage forms.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Febantel oral dosage forms. 520.903 Section 520...) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.903 Febantel oral dosage forms....

  11. 21 CFR 520.1448 - Monensin oral dosage forms.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Monensin oral dosage forms. 520.1448 Section 520...) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.1448 Monensin oral dosage forms. Monensin, as the base or the sodium salt, contains a minimum of 90 percent...

  12. 21 CFR 520.1242 - Levamisole hydrochloride oral dosage forms.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Levamisole hydrochloride oral dosage forms. 520... SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.1242 Levamisole hydrochloride oral dosage forms....

  13. 21 CFR 520.2520 - Trichlorfon oral dosage forms.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Trichlorfon oral dosage forms. 520.2520 Section... (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.2520 Trichlorfon oral dosage forms....

  14. 21 CFR 520.1450 - Morantel tartrate oral dosage forms.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Morantel tartrate oral dosage forms. 520.1450... (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.1450 Morantel tartrate oral dosage forms....

  15. 21 CFR 520.2220 - Sulfadimethoxine oral dosage forms.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Sulfadimethoxine oral dosage forms. 520.2220... (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.2220 Sulfadimethoxine oral dosage forms....

  16. 21 CFR 520.2473 - Tioxidazole oral dosage forms.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Tioxidazole oral dosage forms. 520.2473 Section... (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.2473 Tioxidazole oral dosage forms....

  17. 21 CFR 520.2260 - Sulfamethazine oral dosage forms.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Sulfamethazine oral dosage forms. 520.2260 Section... (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.2260 Sulfamethazine oral dosage forms....

  18. 21 CFR 520.2380 - Thiabendazole oral dosage forms.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Thiabendazole oral dosage forms. 520.2380 Section... (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.2380 Thiabendazole oral dosage forms....

  19. 21 CFR 520.2325 - Sulfaquinoxaline oral dosage forms.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Sulfaquinoxaline oral dosage forms. 520.2325... (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.2325 Sulfaquinoxaline oral dosage forms....

  20. 21 CFR 520.2123 - Spectinomycin oral dosage forms.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Spectinomycin oral dosage forms. 520.2123 Section... (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.2123 Spectinomycin oral dosage forms....

  1. 21 CFR 520.2345 - Tetracycline oral dosage forms.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Tetracycline oral dosage forms. 520.2345 Section... (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.2345 Tetracycline oral dosage forms....

  2. 21 CFR 520.2150 - Stanozolol oral dosage forms.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Stanozolol oral dosage forms. 520.2150 Section 520...) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.2150 Stanozolol oral dosage forms....

  3. 21 CFR 520.2261 - Sulfamethazine sodium oral dosage forms.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Sulfamethazine sodium oral dosage forms. 520.2261 Section 520.2261 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.2261 Sulfamethazine sodium oral dosage...

  4. 21 CFR 522.313 - Ceftiofur injectable dosage forms.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Ceftiofur injectable dosage forms. 522.313 Section... (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.313 Ceftiofur injectable dosage forms....

  5. 21 CFR 522.1660 - Oxytetracycline injectable dosage forms.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Oxytetracycline injectable dosage forms. 522.1660... (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.1660 Oxytetracycline injectable dosage forms....

  6. 21 CFR 522.1660 - Oxytetracycline injectable dosage forms.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Oxytetracycline injectable dosage forms. 522.1660... (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.1660 Oxytetracycline injectable dosage forms....

  7. 21 CFR 522.90 - Ampicillin injectable dosage forms.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Ampicillin injectable dosage forms. 522.90 Section...) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.90 Ampicillin injectable dosage forms....

  8. 21 CFR 522.313 - Ceftiofur injectable dosage forms.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Ceftiofur injectable dosage forms. 522.313 Section... (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.313 Ceftiofur injectable dosage forms....

  9. 21 CFR 522.313 - Ceftiofur injectable dosage forms.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Ceftiofur injectable dosage forms. 522.313 Section... (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.313 Ceftiofur injectable dosage forms....

  10. 21 CFR 522.313 - Ceftiofur injectable dosage forms.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Ceftiofur injectable dosage forms. 522.313 Section... (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.313 Ceftiofur injectable dosage forms....

  11. 21 CFR 522.1660 - Oxytetracycline injectable dosage forms.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Oxytetracycline injectable dosage forms. 522.1660... (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.1660 Oxytetracycline injectable dosage forms....

  12. 21 CFR 522.313 - Ceftiofur injectable dosage forms.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Ceftiofur injectable dosage forms. 522.313 Section... (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.313 Ceftiofur injectable dosage forms....

  13. 21 CFR 522.1222 - Ketamine hydrochloride injectable dosage forms.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Ketamine hydrochloride injectable dosage forms... SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.1222 Ketamine hydrochloride injectable dosage forms....

  14. 21 CFR 522.2444 - Thiopental injectable dosage forms.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Thiopental injectable dosage forms. 522.2444... (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.2444 Thiopental injectable dosage forms....

  15. 21 CFR 522.1222 - Ketamine hydrochloride injectable dosage forms.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Ketamine hydrochloride injectable dosage forms... SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.1222 Ketamine hydrochloride injectable dosage forms....

  16. 21 CFR 522.1660 - Oxytetracycline injectable dosage forms.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Oxytetracycline injectable dosage forms. 522.1660... (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.1660 Oxytetracycline injectable dosage forms....

  17. 21 CFR 522.1222 - Ketamine hydrochloride injectable dosage forms.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Ketamine hydrochloride injectable dosage forms... SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.1222 Ketamine hydrochloride injectable dosage forms....

  18. 21 CFR 522.1660 - Oxytetracycline injectable dosage forms.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Oxytetracycline injectable dosage forms. 522.1660... (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.1660 Oxytetracycline injectable dosage forms....

  19. 21 CFR 522.960 - Flumethasone injectable dosage forms.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Flumethasone injectable dosage forms. 522.960... (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.960 Flumethasone injectable dosage forms....

  20. 21 CFR 522.1222 - Ketamine hydrochloride injectable dosage forms.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Ketamine hydrochloride injectable dosage forms... SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.1222 Ketamine hydrochloride injectable dosage forms....

  1. [Reexaminations of dosages in Shanghanlun: comparison of the dosages among decoctions, pills and powder formulations].

    PubMed

    Suzuki, Tatsuhiko; Endo, Jiro

    2011-01-01

    This paper reveals the dosages of decoctions in Shanghanlun in relation of pills and powder formulations, and obtains following results. At the first examination of the system of weight, while Taohongjing shows three kinds of system of weight; [(1)1liang is equivalent to 14 g. (2) 1liang = 7 g (3) 1liang = 1.4 g], he describes the necessity of the corrective system of weight among the decoctions, the pills and the powder formulations. After Song dynasty, Zhusanfa, which is the method of preparing the decoction by placing powder ingredients of prescriptions in water and simmer, have been mainly adopted. In the term of Zhusanfa, although the whole quantities of prescriptions are written with the ancient weight unit, the notation of the dosage is indicated by the current weight unit, Qian. In Shanghanlun, since the dosage form seems to have been changed from the pills or the powders into the decoction, some of decoctions contain impractical dose for decoction.

  2. Alcohol, aggression and assertiveness in men: dosage and expectancy effects.

    PubMed

    Kreutzer, J S; Schneider, H G; Myatt, C R

    1984-05-01

    The effect of alcohol on aggression and assertiveness was examined in 54 men college students. A 2 (high vs low dosage expectancy) x 3 (0.0, 0.5 and 1.0 ml of 95% alcohol per kg of body weight) design was used. There was an increase in self-reported aggression at the moderate dosage but an increase only in profanity at the high dosage. The expectancy manipulation also produced an increase in self-reported aggression. Actual dosage and dosage expectancy did not influence assertiveness.

  3. [Formulation strategies of intraoral dosage forms].

    PubMed

    Kállai, Nikolett; Sebestyén, Zita; Szabó, Barnabás; Simon, Viktória; Antal, István; Zelkó, Romána

    2012-01-01

    The active pharmaceutical ingredient can be administered by several different routes. Although the oral route (per os) has been one of the most convenient and widely accepted delivery system for most drugs, it has number of disadvantages like the very low pH of the stomach, the high enzymatic activity, and extensive first-pass metabolism. Difficulty in swallowing (dysphagia) is common among all age groups, especially in "problematic" subpopulations like children and the elderly. Several novel intraoral dosage forms (IODs) have recently become available to modulate the physicochemical and pharmacokinetic characteristics of drugs, while improving patient compliance. The present article summarizes and categorizes their formulation possibilities.

  4. Fluoxetine and sertraline dosages in major depression.

    PubMed

    Cantrell, R; Gillespie, W; Altshuler, L

    1999-01-01

    In a retrospective study, we sought to determine medication dosages usually prescribed to obtain euthymia in 59 outpatients with a diagnosis of major depression treated with fluoxetine or sertraline. Charts of veterans admitted to the outpatient mental health clinic at the West Los Angeles Veterans Hospital with a diagnosis of major depression and treated with either fluoxetine or sertraline were reviewed. Progress notes were analyzed for a 6-month time period after the initiation of the medication treatment, and improvement was rated by a physician blind to the drug used for treatment. No significant differences were found in overall response rates between the fluoxetine (81% responders) and sertraline (76% responders) groups. Eighty-one percent of the fluoxetine responders compared to 32% of sertraline responders were at the manufacturer's recommended starting dose (MRSD) at the time of clinical response. One-third of patients receiving sertraline were started on or rapidly titrated to more than 50 mg/day. When only those patients receiving an adequate trial of sertraline at 50 mg were considered, 47% required a dose increase to achieve a remission. These data suggest that 50 mg of sertraline may be inadequate for some patients to achieve a resolution of symptoms of major depression and that many clinicians currently prescribe in a manner suggesting that they believe the MRSD is a suboptimal dosage.

  5. Influence des interactions du couple ciment/adjuvant dispersant sur les proprietes des betons: Importance du mode d'introduction des adjuvants

    NASA Astrophysics Data System (ADS)

    Baalbaki, Moussa

    1998-12-01

    avec le superplastifiant PAE. Le superplastifiant PNS et son adsorption n'est pas fonction de la teneur en C3A. Un resultat tres important est la concentration en calcium qui est beaucoup plus elevee avec le superplastifiant PNS, surtout avec le ciment a forte teneur en C3A. Il semble que l'hydratation des phases du ciment soit controlee par la presence du superplastifiant PAE. Les analyses au microscope electronique a balayage avec le superplastifiant a base de polyacrylate apres 60 minutes d'hydratation du ciment montre de facon tres nette que la surface des grains de ciment est denudee de tout produit d'hydratation. En ce qui concerne les reducteurs d'eau, l'ajout en mode differe produit un certain effet benefique sur la rheologie et depend aussi du dosage surtout avec le reducteur d'eau de portee moyenne a base de lignosulfonate modifie (LM). Dans tous les cas, le reducteur d'eau ordinaire CG retarde plus la prise que le reducteur d'eau de portee moyenne LM. (Abstract shortened by UMI.)

  6. X Chromosome and Autosome Dosage Responses in Drosophila melanogaster Heads.

    PubMed

    Chen, Zhen-Xia; Oliver, Brian

    2015-04-07

    X chromosome dosage compensation is required for male viability in Drosophila. Dosage compensation relative to autosomes is two-fold, but this is likely to be due to a combination of homeostatic gene-by-gene regulation and chromosome-wide regulation. We have baseline values for gene-by-gene dosage compensation on autosomes, but not for the X chromosome. Given the evolutionary history of sex chromosomes, these baseline values could differ. We used a series of deficiencies on the X and autosomes, along with mutations in the sex-determination gene transformer-2, to carefully measure the sex-independent X-chromosome response to gene dosage in adult heads by RNA sequencing. We observed modest and indistinguishable dosage compensation for both X chromosome and autosome genes, suggesting that the X chromosome is neither inherently more robust nor sensitive to dosage change.

  7. [Influence of biological activated carbon dosage on landfill leachate treatment].

    PubMed

    Cui, Yan-Rui; Guo, Yan; Wu, Qing

    2014-08-01

    Effects of biological activated carbon (BAC) dosage on COD removal in landfill leachate treatment were compared. The COD removal efficiency of reactors with 0, 100 and 300 g activated carbon dosage per litre activated sludge was 12.9%, 19.6% and 27.7%, respectively. The results indicated that BAC improved the refractory organic matter removal efficiency and there was a positive correlation between COD removal efficiency and BAC dosage. The output of carbon dioxide after 8h of aeration in reactors was 109, 193 and 306 mg corresponding to the activated carbon dosages mentioned above, which indicated the amount of biodegradation and BAC dosage also had a positive correlation. The combination of adsorption and bioregeneration of BAC resulted in the positive correlation betweem organic matter removal efficiency and BAC dosage, and bioregeneration was the root cause for the microbial decomposition of refractory organics.

  8. Determining aminoglycoside dosage and blood levels using a programmable calculator.

    PubMed

    Ng, P K

    1980-02-01

    A programmable calculator procedure for the determination of dosage regimens and steady-state peak and trough levels of aminoglycoside antibiotics is described. The calculator is programmed based on a one-compartment open model and first-order elimination of aminoglycosides. A detailed description of the programs and user instructions are presented. The programs allow calculation of intermittent i.v. infusion dosage regimens and steady-state levels, and adjustment of dosage and dosing interval when measured plasma levels differ significantly from predicted levels. The calculator programs provide a rapid means of predicting and modifying dosage regimens and steady-state plasma levels for aminoglycoside antibiotics.

  9. Adherence and Dosage Contributions to Parenting Program Quality

    PubMed Central

    Gross, Thomas J.; Mason, W. Alex; Parra, Gilbert; Oats, Robert; Ringle, Jay; Haggerty, Kevin P.

    2015-01-01

    Objective The 3 most frequently examined elements of treatment fidelity are adherence, dosage, and quality. The relationships between these fidelity elements are complex, and additional research is needed to provide clarity. Improving clarity may be especially relevant to parenting programs, which tend to include direct explicit instruction (DEI) elements (i.e., instruction, modeling, and practice). The adherence to and dosage of these DEI elements are frequently assumed to improve program quality; however, little information is available to determine if such adherence and dosage affect program quality. This study examines whether adherence to and dosage of DEI elements predict quality ratings for a widely disseminated, manualized parenting program. Method Adherence is defined as the percentage of intervention tasks completed for each DEI element. Dosage is defined as the number of minutes and seconds spent in each intervention DEI element. Treatment fidelity is assessed for 36 of 144 sessions across 10 program facilitators. A hierarchical linear regression analysis examines the contributions of adherence and dosage in the prediction of session quality ratings. Results The analysis indicates that adherence accounts for a significant proportion of the variance (26%), whereas dosage contributes a nonsignificant proportion of variance (11%). Adherence to skill practice was the strongest individual predictor (β = .445, p < .01). Conclusions Findings suggest that ensuring a high degree of adherence can contribute to quality program delivery. However, more exploration is needed to better understand the ways in which adherence and dosage of DEI elements affect program quality. PMID:26726301

  10. 21 CFR 526.1696 - Penicillin intramammary dosage forms.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Penicillin intramammary dosage forms. 526.1696 Section 526.1696 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS INTRAMAMMARY DOSAGE FORMS § 526.1696...

  11. 21 CFR 526.1696 - Penicillin intramammary dosage forms.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Penicillin intramammary dosage forms. 526.1696 Section 526.1696 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Penicillin intramammary dosage forms....

  12. 21 CFR 520.1696 - Penicillin oral dosage forms.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Penicillin oral dosage forms. 520.1696 Section 520.1696 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.1696 Penicillin...

  13. 21 CFR 526.1696 - Penicillin intramammary dosage forms.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Penicillin intramammary dosage forms. 526.1696 Section 526.1696 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Penicillin intramammary dosage forms....

  14. 21 CFR 520.1696 - Penicillin oral dosage forms.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Penicillin oral dosage forms. 520.1696 Section 520.1696 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.1696 Penicillin...

  15. 21 CFR 526.1696 - Penicillin intramammary dosage forms.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Penicillin intramammary dosage forms. 526.1696 Section 526.1696 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Penicillin intramammary dosage forms....

  16. 21 CFR 520.1696 - Penicillin oral dosage forms.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Penicillin oral dosage forms. 520.1696 Section 520.1696 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.1696 Penicillin...

  17. 21 CFR 526.1696 - Penicillin intramammary dosage forms.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Penicillin intramammary dosage forms. 526.1696 Section 526.1696 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Penicillin intramammary dosage forms....

  18. 21 CFR 520.970 - Flunixin oral dosage forms.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Flunixin oral dosage forms. 520.970 Section 520.970 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.970 Flunixin...

  19. 21 CFR 520.905 - Fenbendazole oral dosage forms.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Fenbendazole oral dosage forms. 520.905 Section 520.905 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Fenbendazole oral dosage forms....

  20. 21 CFR 520.905 - Fenbendazole oral dosage forms.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Fenbendazole oral dosage forms. 520.905 Section 520.905 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Fenbendazole oral dosage forms....

  1. 21 CFR 520.90 - Ampicillin oral dosage forms.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Ampicillin oral dosage forms. 520.90 Section 520.90 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.90 Ampicillin...

  2. 21 CFR 520.300 - Cambendazole oral dosage forms.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Cambendazole oral dosage forms. 520.300 Section 520.300 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS §...

  3. 21 CFR 520.88 - Amoxicillin oral dosage forms.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Amoxicillin oral dosage forms. 520.88 Section 520.88 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.88 Amoxicillin...

  4. 21 CFR 520.82 - Aminopropazine fumarate oral dosage forms.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Aminopropazine fumarate oral dosage forms. 520.82 Section 520.82 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS §...

  5. 21 CFR 520.154 - Bacitracin oral dosage forms.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Bacitracin oral dosage forms. 520.154 Section 520.154 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.154 Bacitracin...

  6. 21 CFR 520.622 - Diethylcarbamazine citrate oral dosage forms.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Diethylcarbamazine citrate oral dosage forms. 520.622 Section 520.622 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS §...

  7. 21 CFR 520.620 - Diethylcarbamazine oral dosage forms.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Diethylcarbamazine oral dosage forms. 520.620 Section 520.620 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS §...

  8. 21 CFR 520.763 - Dithiazanine iodide oral dosage forms.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Dithiazanine iodide oral dosage forms. 520.763 Section 520.763 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS §...

  9. 21 CFR 520.45 - Albendazole oral dosage forms.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

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

  10. 21 CFR 520.540 - Dexamethasone oral dosage forms.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Dexamethasone oral dosage forms. 520.540 Section 520.540 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS §...

  11. 21 CFR 520.445 - Chlortetracycline oral dosage forms.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Chlortetracycline oral dosage forms. 520.445 Section 520.445 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS §...

  12. 21 CFR 520.390 - Chloramphenicol oral dosage forms.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Chloramphenicol oral dosage forms. 520.390 Section 520.390 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS §...

  13. 21 CFR 520.620 - Diethylcarbamazine oral dosage forms.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Diethylcarbamazine oral dosage forms. 520.620 Section 520.620 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Diethylcarbamazine oral dosage forms....

  14. 21 CFR 520.622 - Diethylcarbamazine citrate oral dosage forms.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Diethylcarbamazine citrate oral dosage forms. 520.622 Section 520.622 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... Diethylcarbamazine citrate oral dosage forms....

  15. 21 CFR 520.2160 - Styrylpyridinium, diethylcarbamazine oral dosage forms.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Styrylpyridinium, diethylcarbamazine oral dosage forms. 520.2160 Section 520.2160 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND... § 520.2160 Styrylpyridinium, diethylcarbamazine oral dosage forms....

  16. 21 CFR 520.2160 - Styrylpyridinium, diethylcarbamazine oral dosage forms.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Styrylpyridinium, diethylcarbamazine oral dosage forms. 520.2160 Section 520.2160 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND... § 520.2160 Styrylpyridinium, diethylcarbamazine oral dosage forms....

  17. 21 CFR 520.620 - Diethylcarbamazine oral dosage forms.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Diethylcarbamazine oral dosage forms. 520.620 Section 520.620 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Diethylcarbamazine oral dosage forms....

  18. 21 CFR 520.622 - Diethylcarbamazine citrate oral dosage forms.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Diethylcarbamazine citrate oral dosage forms. 520.622 Section 520.622 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... Diethylcarbamazine citrate oral dosage forms....

  19. 21 CFR 520.620 - Diethylcarbamazine oral dosage forms.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Diethylcarbamazine oral dosage forms. 520.620 Section 520.620 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Diethylcarbamazine oral dosage forms....

  20. 21 CFR 520.2160 - Styrylpyridinium, diethylcarbamazine oral dosage forms.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Styrylpyridinium, diethylcarbamazine oral dosage forms. 520.2160 Section 520.2160 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND... § 520.2160 Styrylpyridinium, diethylcarbamazine oral dosage forms....

  1. 21 CFR 520.2160 - Styrylpyridinium, diethylcarbamazine oral dosage forms.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Styrylpyridinium, diethylcarbamazine oral dosage forms. 520.2160 Section 520.2160 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND... § 520.2160 Styrylpyridinium, diethylcarbamazine oral dosage forms....

  2. 21 CFR 520.2160 - Styrylpyridinium, diethylcarbamazine oral dosage forms.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Styrylpyridinium, diethylcarbamazine oral dosage forms. 520.2160 Section 520.2160 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND... § 520.2160 Styrylpyridinium, diethylcarbamazine oral dosage forms....

  3. 21 CFR 520.622 - Diethylcarbamazine citrate oral dosage forms.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Diethylcarbamazine citrate oral dosage forms. 520.622 Section 520.622 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... Diethylcarbamazine citrate oral dosage forms....

  4. 21 CFR 520.622 - Diethylcarbamazine citrate oral dosage forms.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Diethylcarbamazine citrate oral dosage forms. 520.622 Section 520.622 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... Diethylcarbamazine citrate oral dosage forms....

  5. 21 CFR 520.620 - Diethylcarbamazine oral dosage forms.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Diethylcarbamazine oral dosage forms. 520.620 Section 520.620 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Diethylcarbamazine oral dosage forms....

  6. Stability of dry coated solid dosage forms.

    PubMed

    Kablitz, Caroline Désirée; Urbanetz, Nora Anne

    2009-01-01

    The dry coating process was evaluated in terms of storage stability investigating drug release and agglomeration tendency of the different coated oral dosage forms; hydroxypropyl methylcellulose acetate succinate (HPMCAS) was used with triethylcitrate (TEC) as plasticizer and acetylated monoglyceride (Myvacet) as wetting agent. Talc or colloidal silicon dioxide (Aerosil) was used as anti-tacking agents. In contrast to coating formulations consisting of HPMCAS and Myvacet all formulations containing TEC showed enteric resistance and no agglomeration tendency after preparation. After storage at 10% RH +/- 5% enteric resistance is increased slightly. This increase is more pronounced at 60% RH +/- 5%. The formulations without anti-tacking agents showed higher drug releases after 12 and 24 months due to the damage of the film's integrity during sample preparation caused by the high tackiness of the film. Tackiness is not affected by storing if samples are stored at low relative humidity. At high relative humidity tackiness increases upon storage especially for formulations without anti-tacking agents. The sieving results of the agglomeration measurements after storage can be confirmed by ring shear measurements performed immediately after preparation and approved to be a tool, which is able to predict the agglomeration during storage.

  7. Foreign matter identification from solid dosage forms.

    PubMed

    Pajander, Jari; Haugshøj, Kenneth Brian; Bjørneboe, Kathrine; Wahlberg, Pia; Rantanen, Jukka

    2013-06-01

    Despite the increased request for robust quality systems, the end product may contain unidentified defects or discoloured regions. The foreign matter has to be monitored, identified and its source defined in order to prevent further contamination. However, the identification task can be complicated, since the origin and nature of foreign matter are various. The aim of this study is to provide an efficient foreign matter identification procedure for various substances possibly originating from pharmaceutical manufacturing environment. The surface or cross-section of the uncoated and coated tablets was analysed by utilization of different analytical techniques, such as light microscopy (LM), scanning electron microscopy in combination with energy dispersive X-ray microanalysis (SEM/EDX), Fourier transform infrared spectroscopy (FT-IR) and time-of-flight secondary ion mass spectrometry (ToF-SIMS). The results indicate that the combination of different analytical techniques proved to be a powerful approach in foreign matter identification. Light microscopy and SEM generate information on the morphology of foreign matter particles. EDX provides elemental analysis, which most often serves as final confirmation of the identification. However, FT-IR can be used to obtain information on the compounds chemical structure and conformation, and ToF-SIMS provides sensitivity in cases, where the entire solid dosage form is contaminated with foreign matter.

  8. Medication Dosage in Overweight and Obese Children

    PubMed Central

    Matson, Kelly L.; Horton, Evan R.; Capino, Amanda C.

    2017-01-01

    Approximately 31.8% of U.S. children ages 2 to 19 years are considered overweight or obese. This creates significant challenges to dosing medications that are primarily weight based (mg/kg) and in predicting pharmacokinetics parameters in pediatric patients. Obese individuals generally have a larger volume of distribution for lipophilic medications. Conversely, the Vd of hydrophilic medications may be increased or decreased due to increased lean body mass, blood volume, and decrease percentage of total body water. They may also experience decreased hepatic clearance secondary to fatty infiltrates of the liver. Hence, obesity may affect loading dose, dosage interval, plasma half-life, and time to reach steady-state concentration for various medications. Weight-based dosing is also a cause for potential medication errors. This position statement of the Pediatric Pharmacy Advocacy Group recommends that weight-based dosing should be used in patients ages < 18 years who are < 40 kg; weight-based dosing should be used in patients ≥ 40 kg, unless, unless the recommended adult dose for the specific indication is exceeded; clinicians should use pharmacokinetic analysis for adjusting medications in overweight/obese children; and research efforts continue to evaluate dosing of medications in obese/overweight children.

  9. Individualizing phenytoin dosage regimens using a programmable calculator.

    PubMed

    Ng, P K

    1980-04-01

    A programmable calculator procedure for the determination of individualized phenytoin dosage regimens is described. The calculator is programmed based on a one-compartment, open model using the Michaelis-Menten equation. A detailed description of the programs and user instructions are presented. The programs allow calculation of oral dosage regimens and steady-state phenytoin levels. The first two programs require a given dose and one corresponding steady-state minimum concentration point to estimate a dosage regimen and steady-state serum level. The second two programs, which provide a more accurate prediction of dosage regimen and steady-state serum levels, require two dose and steady-state minimum concentration poits. The calculator programs provide a rapid and reliable means of estimating a patient's phenytoin dosage regimens and steady-state serum levels.

  10. Cri du Chat syndrome.

    PubMed

    Cerruti Mainardi, Paola

    2006-09-05

    The Cri du Chat syndrome (CdCS) is a genetic disease resulting from a deletion of variable size occurring on the short arm of chromosome 5 (5p-). The incidence ranges from 1:15,000 to 1:50,000 live-born infants. The main clinical features are a high-pitched monochromatic cry, microcephaly, broad nasal bridge, epicanthal folds, micrognathia, abnormal dermatoglyphics, and severe psychomotor and mental retardation. Malformations, although not very frequent, may be present: cardiac, neurological and renal abnormalities, preauricular tags, syndactyly, hypospadias, and cryptorchidism. Molecular cytogenetic analysis has allowed a cytogenetic and phenotypic map of 5p to be defined, even if results from the studies reported up to now are not completely in agreement. Genotype-phenotype correlation studies showed a clinical and cytogenetic variability. The identification of phenotypic subsets associated with a specific size and type of deletion is of diagnostic and prognostic relevance. Specific growth and psychomotor development charts have been established. Two genes, Semaphorin F (SEMAF) and delta-catenin (CTNND2), which have been mapped to the "critical regions", are potentially involved in cerebral development and their deletion may be associated with mental retardation in CdCS patients. Deletion of the telomerase reverse transcriptase (hTERT) gene, localised to 5p15.33, could contribute to the phenotypic changes in CdCS. The critical regions were recently refined by using array comparative genomic hybridisation. The cat-like cry critical region was further narrowed using quantitative polymerase chain reaction (PCR) and three candidate genes were characterised in this region. The diagnosis is based on typical clinical manifestations. Karyotype analysis and, in doubtful cases, FISH analysis will confirm the diagnosis. There is no specific therapy for CdCS but early rehabilitative and educational interventions improve the prognosis and considerable progress has been made

  11. Cri du Chat syndrome

    PubMed Central

    Cerruti Mainardi, Paola

    2006-01-01

    The Cri du Chat syndrome (CdCS) is a genetic disease resulting from a deletion of variable size occurring on the short arm of chromosome 5 (5p-). The incidence ranges from 1:15,000 to 1:50,000 live-born infants. The main clinical features are a high-pitched monochromatic cry, microcephaly, broad nasal bridge, epicanthal folds, micrognathia, abnormal dermatoglyphics, and severe psychomotor and mental retardation. Malformations, although not very frequent, may be present: cardiac, neurological and renal abnormalities, preauricular tags, syndactyly, hypospadias, and cryptorchidism. Molecular cytogenetic analysis has allowed a cytogenetic and phenotypic map of 5p to be defined, even if results from the studies reported up to now are not completely in agreement. Genotype-phenotype correlation studies showed a clinical and cytogenetic variability. The identification of phenotypic subsets associated with a specific size and type of deletion is of diagnostic and prognostic relevance. Specific growth and psychomotor development charts have been established. Two genes, Semaphorin F (SEMAF) and δ-catenin (CTNND2), which have been mapped to the "critical regions", are potentially involved in cerebral development and their deletion may be associated with mental retardation in CdCS patients. Deletion of the telomerase reverse transcriptase (hTERT) gene, localised to 5p15.33, could contribute to the phenotypic changes in CdCS. The critical regions were recently refined by using array comparative genomic hybridisation. The cat-like cry critical region was further narrowed using quantitative polymerase chain reaction (PCR) and three candidate genes were characterised in this region. The diagnosis is based on typical clinical manifestations. Karyotype analysis and, in doubtful cases, FISH analysis will confirm the diagnosis. There is no specific therapy for CdCS but early rehabilitative and educational interventions improve the prognosis and considerable progress has been made in

  12. The transit of dosage forms through the small intestine.

    PubMed

    Yuen, Kah-Hay

    2010-08-16

    The human small intestine, with its enormous absorptive surface area, is invariably the principal site of drug absorption. Hence, the residence time of a dosage form in this part of the gut can have a great influence on the absorption of the contained drug. Various methods have been employed to monitor the gastrointestinal transit of pharmaceutical dosage forms, but the use of gamma-scintigraphy has superceded all the other methods. However, careful consideration of the time interval for image acquisition and proper analysis of the scintigraphic data are important for obtaining reliable results. Most studies reported the mean small intestinal transit time of various dosage forms to be about 3-4h, being closely similar to that of food and water. The value does not appear to be influenced by their physical state nor the presence of food, but the timing of food intake following administration of the dosage forms can influence the small intestinal transit time. While the mean small intestinal transit time is quite consistent among dosage forms and studies, individual values can vary widely. There are differing opinions regarding the effect of density and size of dosage forms on their small intestinal transit properties. Some common excipients employed in pharmaceutical formulations can affect the small intestinal transit and drug absorption. There is currently a lack of studies regarding the effects of excipients, as well as the timing of food intake on the small intestinal transit of dosage forms and drug absorption.

  13. Applications attract DuPont

    SciTech Connect

    Rotman, D.

    1996-08-07

    Scientists at DuPont say they have demonstrated the first chemical processing application for high-temperature superconducting (HTS) magnets. DuPont says the work, which uses a HTS magnet to separate mineral contaminants from kaolin, points to the feasibility of a range of HTS applications in industrial processing, including those involving polymerization. DuPont`s success comes after 10 years of work to commercialize high-temperature superconductors. And while superconductors have lost much of their luster since the late 1980s, the company says it is still bullish on their prospects. {open_quotes}At the moment, there`s no real market for superconductors,{close_quotes} says Alan Lauder, general manager/superconductivity. But, he says, several potentially lucrative applications could be commercialized within the next several years.

  14. L'Aventure du LHC

    SciTech Connect

    2010-06-11

    Cette présentation s’adressera principalement aux personnes qui ont construit le LHC. La construction du LHC fut longue et difficile. De nombreux problèmes sont apparus en cours de route. Tous ont été résolus grâce au dévouement et à l’engagement du personnel et des collaborateurs. Je reviendrai sur les coups durs et les réussites qui ont marqués ces 15 dernières années et je vous montrerai combien cette machine, le fruit de vos efforts, est extraordinaire.

  15. Poumon du puisatier

    PubMed Central

    Elidrissi, Amal Moustarhfir; Zaghba, Nahid; Benjelloun, Hanane; Yassine, Najiba

    2016-01-01

    Le puisatier a pour profession le creusement et l'entretien des puits pour fournir de l'eau. Il est au contact de divers minerais, particulièrement la silice, particule qui présente un risque certain de développement des maladies pulmonaires connues sous le nom de silicose. Le but de notre travail est de préciser le profil épidémiologique, clinique, radiologique et évolutif des patients puisatiers silicotiques. C'est une étude rétrospective concernant 54 cas de puisatiers ayant une silicose, colligés au service des maladies respiratoires du CHU Ibn Rochd de Casablanca, de Mars 1997 à Janvier 2016. Tous les malades étaient des puisatiers, de sexe masculin, avec une moyenne d'âge de 50 ans. Le tabagisme était retrouvé dans 36 cas et un antécédent de tuberculose était noté dans huit cas. La radiographie thoracique retrouvait des grandes opacités dans 39 cas, des petites opacités dans 15 cas, et un épaississement des septats dans 11 cas. Ce tableau de silicose s'était compliqué d'une surinfection bactérienne dans 37% des cas, d' un pneumothorax dans 4% des cas et d'une tuberculose dans 20% des cas. La prise en charge thérapeutique était celle des complications. La déclaration de la maladie professionnelle et de l'indemnisation était faite. L'évolution était bonne dans 12 cas, stationnaire dans 17 cas et mauvaise dans 16 cas. La silicose est une pneumoconiose fréquente chez les puisatiers. Elle retentit sur la fonction respiratoire. Nous soulignons l'association fréquente de tuberculose et nous insistons sur la prévention qui reste le meilleur traitement. PMID:28292119

  16. Automatic identification and normalization of dosage forms in drug monographs

    PubMed Central

    2012-01-01

    Background Each day, millions of health consumers seek drug-related information on the Web. Despite some efforts in linking related resources, drug information is largely scattered in a wide variety of websites of different quality and credibility. Methods As a step toward providing users with integrated access to multiple trustworthy drug resources, we aim to develop a method capable of identifying drug's dosage form information in addition to drug name recognition. We developed rules and patterns for identifying dosage forms from different sections of full-text drug monographs, and subsequently normalized them to standardized RxNorm dosage forms. Results Our method represents a significant improvement compared with a baseline lookup approach, achieving overall macro-averaged Precision of 80%, Recall of 98%, and F-Measure of 85%. Conclusions We successfully developed an automatic approach for drug dosage form identification, which is critical for building links between different drug-related resources. PMID:22336431

  17. Initial dosage regimens of gentamicin in patients with burns.

    PubMed

    Zaske, D E; Chin, T; Kohls, P R; Solem, L D; Strate, R G

    1991-01-01

    For 95 patients with burns the gentamicin dosage regimen necessary to achieve optimal serum concentrations was determined. Individual elimination rates and distribution volumes for gentamicin were determined and correlated with renal function parameters and age. In patients with burns who had normal serum creatinine levels (less than 1.5 mg/dl), gentamicin clearance and thus dosage regimens can be stratified by age. Gentamicin's clearance decreased inversely with age. Initial dosage guidelines were calculated for different age groups of patients with normal levels of serum creatinine. The guidelines were developed to assist the clinician in attaining therapeutic concentrations with initial doses of gentamicin. Therapeutic serum concentrations were reached in most patients with burns dosed by these guidelines. Serum gentamicin concentrations should always be monitored during therapy, and dosages should be adjusted to ensure optimal concentrations during the course of therapy.

  18. Buccal Dosage Forms: General Considerations for Pediatric Patients.

    PubMed

    Montero-Padilla, Soledad; Velaga, Sitaram; Morales, Javier O

    2017-02-01

    The development of an appropriate dosage form for pediatric patients needs to take into account several aspects, since adult drug biodistribution differs from that of pediatrics. In recent years, buccal administration has become an attractive route, having different dosage forms under development including tablets, lozenges, films, and solutions among others. Furthermore, the buccal epithelium can allow quick access to systemic circulation, which could be used for a rapid onset of action. For pediatric patients, dosage forms to be placed in the oral cavity have higher requirements for palatability to increase acceptance and therapy compliance. Therefore, an understanding of the excipients required and their functions and properties needs to be particularly addressed. This review is focused on the differences and requirements relevant to buccal administration for pediatric patients (compared to adults) and how novel dosage forms can be less invasive and more acceptable alternatives.

  19. Stability of oral liquid dosage forms of ethacrynic Acid.

    PubMed

    Ling, J; Gupta, V D

    2001-01-01

    The stability of ethacrynic acid (2.5 mg/mL) in oral liquid dosage forms was investigated. Tablets in 0.05 M phosphate buffer (available commercially) in water were used to prepare the dosage forms. The effects of mannitol and sugar on the stability of ethacrynic acid were negligible. There was no change in the physical appearance of the oral liquid dosage forms or pH values during the study. There was, however, a new peak in the chromatogram from the products(s) of decomposition. An oral liquid dosage form of ethacrynic acid containing 0.05 M phosphate buffer and 10% mannitol was stable for 24 days when stored at 5 deg C and for only 3 days when stored at 25 deg C.

  20. Establishing Genetic Interactions by a Synthetic Dosage Lethality Phenotype

    PubMed Central

    Kroll, E. S.; Hyland, K. M.; Hieter, P.; Li, J. J.

    1996-01-01

    We have devised a genetic screen, termed synthetic dosage lethality, in which a cloned ``reference'' gene is inducibly overexpressed in a set of mutant strains carrying potential ``target'' mutations. To test the specificity of the method, two reference genes, CTF13, encoding a centromere binding protein, and ORC6, encoding a subunit of the origin of replication binding complex, were overexpressed in a large collection of mutants defective in either chromosome segregation or replication. CTF13 overexpression caused synthetic dosage lethality in combination with ctf14-42 (cbf2, ndc10), ctf17-61 (chl4), ctf19-58 and ctf19-26. ORC6 overexpression caused synthetic dosage lethality in combination with cdc2-1, cdc6-1, cdc14-1, cdc16-1 and cdc46-1. These relationships reflect specific interactions, as overexpression of CTF13 caused lethality in kinetochore mutants and overexpression of ORC6 caused lethality in replication mutants. In contrast, only one case of dosage suppression was observed. We suggest that synthetic dosage lethality identifies a broad spectrum of interacting mutations and is of general utility in detecting specific genetic interactions using a cloned wild-type gene as a starting point. Furthermore, synthetic dosage lethality is easily adapted to the study of cloned genes in other organisms. PMID:8722765

  1. Bioavailability of intranasal promethazine dosage forms in dogs

    NASA Technical Reports Server (NTRS)

    Ramanathan, R.; Geary, R. S.; Bourne, D. W.; Putcha, L.

    1998-01-01

    Intramuscular promethazine (PMZ) is used aboard the US Space Shuttle to ameliorate symptoms of space motion sickness. Bioavailability after an oral dose of PMZ during space flight is thought to be impaired because of gastrointestinal disturbances associated with weightlessness and space motion sickness. In an attempt to find an alternative dosage form for use in space, we evaluated two intranasal (i.n.) dosage forms of PMZ in dogs for absorption and bioavailability relative to that of an equivalent intramuscular dose. Promethazine (5 mg kg-1) was administered as two intranasal dosage forms and as an intramuscular (i.m.) dose to three dogs in a randomised cross-over design. Serial blood samples were taken and analysed for PMZ concentrations and the absorption and bioavailability of PMZ were calculated for the three dosage forms. PMZ absorption from the carboxymethyl cellulose microsphere i.n. dosage form was more rapid and complete than from the myverol cubic gel formulation or from an i.m. injection. Bioavailability of the microsphere formulation was also greater than that of the gel formulation (AUC 3009 vs 1727 ng h ml-1). The bioavailability of the two i.n. dosage forms (relative to that of the i.m. injection) were 94% (microsphere) and 54% (gel). The i.n. microsphere formulation of PMZ offers great promise as an effective non-invasive alternative for treating space motion sickness due to its rapid absorption and bioavailability equivalent to the i.m. dose.

  2. Rupture sous-cutanée du tendon long extenseur du pouce: à propos de 5 cas

    PubMed Central

    Abdelillah, Rachid; Abbassi, Najib; Erraji, Moncef; Abdeljawad, Najib; Yacoubi, Hicham; Daoudi, Abdelkrim

    2014-01-01

    La rupture spontanée du muscle long extenseur du pouce (EPL) du tendon au niveau du poignet est rare et principalement rapportés après fracture du radius distal à tubercule de Lister, dans la synovite, ténosynovite ou la polyarthrite rhumatoïde. Nous rapportons 5 cas de rupture spontanée du tendon long extenseur du pouce, traités par une greffe ou un transfert tendineux. PMID:25317233

  3. Mammalian X chromosome inactivation evolved as a dosage-compensation mechanism for dosage-sensitive genes on the X chromosome.

    PubMed

    Pessia, Eugénie; Makino, Takashi; Bailly-Bechet, Marc; McLysaght, Aoife; Marais, Gabriel A B

    2012-04-03

    How and why female somatic X-chromosome inactivation (XCI) evolved in mammals remains poorly understood. It has been proposed that XCI is a dosage-compensation mechanism that evolved to equalize expression levels of X-linked genes in females (2X) and males (1X), with a prior twofold increase in expression of X-linked genes in both sexes ("Ohno's hypothesis"). Whereas the parity of X chromosome expression between the sexes has been clearly demonstrated, tests for the doubling of expression levels globally along the X chromosome have returned contradictory results. However, changes in gene dosage during sex-chromosome evolution are not expected to impact on all genes equally, and should have greater consequences for dosage-sensitive genes. We show that, for genes encoding components of large protein complexes (≥ 7 members)--a class of genes that is expected to be dosage-sensitive--expression of X-linked genes is similar to that of autosomal genes within the complex. These data support Ohno's hypothesis that XCI acts as a dosage-compensation mechanism, and allow us to refine Ohno's model of XCI evolution. We also explore the contribution of dosage-sensitive genes to X aneuploidy phenotypes in humans, such as Turner (X0) and Klinefelter (XXY) syndromes. X aneuploidy in humans is common and is known to have mild effects because most of the supernumerary X genes are inactivated and not affected by aneuploidy. Only genes escaping XCI experience dosage changes in X-aneuploidy patients. We combined data on dosage sensitivity and XCI to compute a list of candidate genes for X-aneuploidy syndromes.

  4. A benefit/risk approach towards selecting appropriate pharmaceutical dosage forms - an application for paediatric dosage form selection.

    PubMed

    Sam, Tom; Ernest, Terry B; Walsh, Jennifer; Williams, Julie L

    2012-10-05

    The design and selection of new pharmaceutical dosage forms involves the careful consideration and balancing of a quality target product profile against technical challenges and development feasibility. Paediatric dosage forms present particular complexity due to the diverse patient population, patient compliance challenges and safety considerations of this vulnerable population. This paper presents a structured framework for assessing the comparative benefits and risks of different pharmaceutical design options against pre-determined criteria relating to (1) efficacy, (2) safety and (3) patient access. This benefit/risk framework has then been applied to three hypothetical, but realistic, scenarios for paediatric dosage forms in order to explore its utility in guiding dosage form design and formulation selection. The approach allows a rigorous, systematic and qualitative assessment of the merits and disadvantages of each dosage form option and helps identify mitigating strategies to modify risk. The application of a weighting and scoring system to the criteria depending on the specific case could further refine the analysis and aid decision-making. In this paper, one case study is scored for illustrative purposes. However, it is acknowledged that in real development scenarios, the generation of actual data considering the very specific situation for the patient/product/developer would come into play to drive decisions on the most appropriate dosage form strategy.

  5. L'Aventure du LHC

    ScienceCinema

    None

    2016-07-12

    Cette présentation s’adressera principalement aux personnes qui ont construit le LHC. La construction du LHC fut longue et difficile. De nombreux problèmes sont apparus en cours de route. Tous ont été résolus grâce au dévouement et à l’engagement du personnel et des collaborateurs. Je reviendrai sur les coups durs et les réussites qui ont marqués ces 15 dernières années et je vous montrerai combien cette machine, le fruit de vos efforts, est extraordinaire.

  6. Evolution of vertebrate sex chromosomes and dosage compensation.

    PubMed

    Graves, Jennifer A Marshall

    2016-01-01

    Differentiated sex chromosomes in mammals and other vertebrates evolved independently but in strikingly similar ways. Vertebrates with differentiated sex chromosomes share the problems of the unequal expression of the genes borne on sex chromosomes, both between the sexes and with respect to autosomes. Dosage compensation of genes on sex chromosomes is surprisingly variable - and can even be absent - in different vertebrate groups. Systems that compensate for different gene dosages include a wide range of global, regional and gene-by-gene processes that differ in their extent and their molecular mechanisms. However, many elements of these control systems are similar across distant phylogenetic divisions and show parallels to other gene silencing systems. These dosage systems cannot be identical by descent but were probably constructed from elements of ancient silencing mechanisms that are ubiquitous among vertebrates and shared throughout eukaryotes.

  7. The UDCA dosage deficit: a fate shared with CDCA.

    PubMed

    Roda, Enrico; Liva, Stefania; Ferrara, Francesco; Azzaroli, Francesco; Giovanelli, Silvia; Nigro, Giovanni; Festi, Davide; Mazzella, Giuseppe

    2002-03-01

    Ursodeoxycholic acid (UDCA) is used both as the treatment of choice in many cholestatic syndromes and as complementary therapy in many liver diseases. However, few dose-finding studies exist, and none has evaluated the efficacy and long-term safety of UDCA therapy in primary biliary cirrhosis (PBC). There is an open debate about UDCA's impact on the natural history of PBC, and no universal evidence of benefits on the major endpoint exists. This is perhaps due to a UDCA dosage deficit. Most clinical trials on PBC therapy have used conservative dosages of UDCA similar to those of chenodeoxycholic acid (CDCA) used for dissolution of gallstones. It may be necessary to re-evaluate the dosage of UDCA that provides the most effective treatment.

  8. Design of initial dosage regimen using a programmable calculator.

    PubMed

    Ritschel, W A; Eldon, M A

    1985-07-01

    A programmable calculator procedure for the determination of dosage regimens to achieve desired steady state concentrations is described. The dosage regimen prediction is based on data from the literature on pharmacokinetic parameters of drugs and correction factors specific for the patient's condition, such as renal failure, geriatric patient and congestive heart failure. The program is designed to generate dosage regimens based on desired steady state trough level, desired steady state peak level, desired mean steady state level, or to fluctuate between desired steady state peak and trough levels. The program can be used for I.V. and extravascular route of administration. A detailed program description and user instructions are presented and illustrated by three examples.

  9. Biowaiver monographs for immediate release solid oral dosage forms: prednisolone.

    PubMed

    Vogt, M; Derendorf, H; Krämer, J; Junginger, H E; Midha, K K; Shah, V P; Stavchansky, S; Dressman, J B; Barends, D M

    2007-01-01

    Literature data relevant to the decision to allow a waiver of in vivo bioequivalence (BE) testing for the approval of immediate release (IR) solid oral dosage forms containing prednisolone are reviewed. Data on its solubility, oral absorption, and permeability are not totally conclusive, but strongly suggest a BCS Class 1 classification. Prednisolone's therapeutic indications and therapeutic index, pharmacokinetics, and the possibility of excipient interactions were also taken into consideration. Available evidence indicates that a biowaiver for IR solid oral dosage forms formulated with the excipients tabulated in this article would be unlikely to expose patients to undue risks.

  10. Métastases gastro-intestinales du cancer du sein: à propos de 2 cas

    PubMed Central

    Loubna, Mezouar; Mohamed, El Hfid; Tijani, El Harroudi; Fouzia, Ghadouani; Hanane, Haj Kacem; Zouhour, Bourhaleb; Asmae, Ouabdelmoumen

    2013-01-01

    Le cancer du sein est le cancer le plus fréquent chez la femme, notamment au Maroc, avec un taux de mortalité élevé. Les métastases gastro-intestinales d'un carcinome canalaire du sein sont rares. Leur diagnostic est difficile du fait de la nature non spécifique des symptômes. Nous rapportons deux observations originales de métastases gastroduodénales d'un cancer canalaire infiltrant du sein. Les métastases gastro-intestinales du cancer du sein sont très rares; la présence de symptômes gastro-intestinaux chez une malade ayant un antécédent de cancer du sein doit faire suspecter une atteinte métastatique gastro-intestinale. PMID:24198876

  11. Narrative Language Intervention Intensity and Dosage: Telling the Whole Story

    ERIC Educational Resources Information Center

    Hoffman, LaVae M.

    2009-01-01

    This article expands on the work of S. F. Warren, M. E. Fey, and P. J. Yoder (2007) by applying their suggested intervention-intensity parameters to narrative language intervention with school-aged children. These pharmacologically based dosage concepts are examined from two perspectives: oral narrative skills as the target of language therapy and…

  12. Calculating Dosages: A Programed Learner for Student Nurses.

    ERIC Educational Resources Information Center

    Hare, Mary

    Intended for nursing students, this programed workbook contains learning exercises and study tests on using household, apothecary, and metric systems in calculating medication dosages. The material, organized in six learning units, was designed to help students meet six objectives: correctly interpret and use accepted symbols and abbreviations in…

  13. 77 FR 15961 - Oral Dosage Form New Animal Drugs; Phenylpropanolamine

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-03-19

    ... HUMAN SERVICES Food and Drug Administration 21 CFR Part 520 Oral Dosage Form New Animal Drugs; Phenylpropanolamine AGENCY: Food and Drug Administration, HHS. ACTION: Final rule. SUMMARY: The Food and Drug Administration (FDA) is amending the animal drug regulations to reflect approval of an original new animal...

  14. 77 FR 3927 - Oral Dosage Form New Animal Drugs; Deracoxib

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-26

    ... HUMAN SERVICES Food and Drug Administration 21 CFR Part 520 Oral Dosage Form New Animal Drugs; Deracoxib AGENCY: Food and Drug Administration, HHS. ACTION: Final rule. SUMMARY: The Food and Drug Administration (FDA) is amending the animal drug regulations to reflect approval of a supplemental new animal...

  15. Software for Dosage Individualization of Voriconazole for Immunocompromised Patients

    PubMed Central

    VanGuilder, Michael; Donnelly, J. Peter; Blijlevens, Nicole M. A.; Brüggemann, Roger J. M.; Jelliffe, Roger W.; Neely, Michael N.

    2013-01-01

    The efficacy of voriconazole is potentially compromised by considerable pharmacokinetic variability. There are increasing insights into voriconazole concentrations that are safe and effective for treatment of invasive fungal infections. Therapeutic drug monitoring is increasingly advocated. Software to aid in the individualization of dosing would be an extremely useful clinical tool. We developed software to enable the individualization of voriconazole dosing to attain predefined serum concentration targets. The process of individualized voriconazole therapy was based on concepts of Bayesian stochastic adaptive control. Multiple-model dosage design with feedback control was used to calculate dosages that achieved desired concentration targets with maximum precision. The performance of the software program was assessed using the data from 10 recipients of an allogeneic hematopoietic stem cell transplant (HSCT) receiving intravenous (i.v.) voriconazole. The program was able to model the plasma concentrations with a high level of precision, despite the wide range of concentration trajectories and interindividual pharmacokinetic variability. The voriconazole concentrations predicted after the last dosages were largely concordant with those actually measured. Simulations provided an illustration of the way in which the software can be used to adjust dosages of patients falling outside desired concentration targets. This software appears to be an extremely useful tool to further optimize voriconazole therapy and aid in therapeutic drug monitoring. Further prospective studies are now required to define the utility of the controller in daily clinical practice. PMID:23380734

  16. 21 CFR 201.55 - Statement of dosage.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 4 2010-04-01 2010-04-01 false Statement of dosage. 201.55 Section 201.55 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS: GENERAL LABELING Labeling Requirements for Prescription Drugs and/or Insulin § 201.55 Statement of...

  17. Health Instruction Packages: Drug Dosage, Classification, and Mixing.

    ERIC Educational Resources Information Center

    Bracchi, Dorothy P.; And Others

    Text, illustrations, and exercises are utilized in a set of seven learning modules to instruct nursing students in the fundamentals of drug classification, dosage, and mixing. The first module, by Dorothy Bracchi, teaches the student to identify six classifications of medication often administered to orthopedic patients: anti-neurospasmolytic…

  18. Recent progress and open questions in Drosophila dosage compensation

    PubMed Central

    Vensko, Steven P; Stone, Eric A

    2015-01-01

    Sexual dimorphism is observed in many traits across diverse taxa, and often it is quite extreme. Within a species, individuals of opposing sex can appear strikingly different, reflecting differences at the molecular level that may be similarly striking. Among the most extreme cases of such molecular sexual dimorphism is the quantity of sex chromosomes that each sex possesses. Hemizygous sex chromosomes are common to many species, and various mechanisms have evolved to regulate transcriptional activity to ensure appropriate sex chromosome-to-autosome gene expression stoichiometry. Among the most thoroughly investigated of these mechanisms is Drosophila melanogaster's male-specific lethal (MSL) complex-mediated dosage compensation. In Drosophila, the male X chromosome transcription is upregulated approximately two-fold in somatic tissues to counterbalance the effects of sex chromosome hemizygosity on transcript abundance. Despite dramatic advances in our understanding of the Drosophila dosage compensation, many questions remain unanswered, and our understanding of its molecular underpinnings remains incomplete. In this review, we synthesize recent progress in the field as a means to highlight open questions, including how the MSL complex targets the X chromosome, how dosage compensation has shaped evolution of X-linked genes, and the degree to which MSL complex-mediated dosage compensation varies in activity across somatic tissues. PMID:26213294

  19. 76 FR 78149 - Oral Dosage Form New Animal Drugs; Estriol

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-16

    ... HUMAN SERVICES Food and Drug Administration 21 CFR Part 520 Oral Dosage Form New Animal Drugs; Estriol AGENCY: Food and Drug Administration, HHS. ACTION: Final rule. SUMMARY: The Food and Drug Administration (FDA) is amending the animal drug regulations to reflect approval of an original new animal...

  20. 77 FR 15960 - Oral Dosage Form New Animal Drugs; Pergolide

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-03-19

    ... HUMAN SERVICES Food and Drug Administration 21 CFR Part 520 Oral Dosage Form New Animal Drugs; Pergolide AGENCY: Food and Drug Administration, HHS. ACTION: Final rule. SUMMARY: The Food and Drug Administration (FDA) is amending the animal drug regulations to reflect approval of an original new animal...

  1. 75 FR 67031 - Oral Dosage Form New Animal Drugs; Domperidone

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-01

    ... HUMAN SERVICES Food and Drug Administration 21 CFR Part 520 Oral Dosage Form New Animal Drugs; Domperidone AGENCY: Food and Drug Administration, HHS. ACTION: Final rule. SUMMARY: The Food and Drug Administration (FDA) is amending the animal drug regulations to reflect the original approval of a new...

  2. 76 FR 59023 - Oral Dosage Form New Animal Drugs; Tylosin

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-23

    ... HUMAN SERVICES Food and Drug Administration 21 CFR Part 520 Oral Dosage Form New Animal Drugs; Tylosin AGENCY: Food and Drug Administration, HHS. ACTION: Final rule. SUMMARY: The Food and Drug Administration (FDA) is amending the animal drug regulations to reflect approval of an original abbreviated new...

  3. 76 FR 40808 - Oral Dosage Form New Animal Drugs; Amprolium

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-12

    ... HUMAN SERVICES Food and Drug Administration 21 CFR Part 520 Oral Dosage Form New Animal Drugs; Amprolium AGENCY: Food and Drug Administration, HHS. ACTION: Final rule. SUMMARY: The Food and Drug Administration (FDA) is amending the animal drug regulations to reflect approval of an original abbreviated new...

  4. Biowaiver monographs for immediate release solid oral dosage forms: levofloxacin.

    PubMed

    Koeppe, Marcelle O; Cristofoletti, Rodrigo; Fernandes, Eduardo F; Storpirtis, Silvia; Junginger, Hans E; Kopp, Sabine; Midha, Kamal K; Shah, Vinod P; Stavchansky, Salomon; Dressman, Jennifer B; Barends, Dirk M

    2011-05-01

    Literature data relevant to the decision to allow a waiver of in vivo bioequivalence (BE) testing for the approval of immediate release (IR) solid oral dosage forms containing levofloxacin as the only active pharmaceutical ingredient (API) are reviewed. According to the current Biopharmaceutics Classification System, levofloxacin can be assigned to Class I. No problems with BE of IR levofloxacin formulations containing different excipients and produced by different manufacturing methods have been reported and hence the risk of bioinequivalence caused by these factors appears to be low. In addition, levofloxacin has a wide therapeutic index. On the basis of this evidence, a biowaiver is recommended for IR solid oral dosage forms containing levofloxacin as the single API provided that (a) the test product contains only excipients present in IR levofloxacin drug products that have been approved in International Conference on Harmonization (ICH) or associated countries and which have the same dosage form; (b) both the test and comparator dosage form are "very rapidly dissolving" or "rapidly dissolving" with similarity of the dissolution profiles demonstrated at pH 1.2, 4.5, and 6.8; and (c) if the test product contains polysorbates, it should be both qualitatively and quantitatively identical to its comparator in terms of polysorbate content.

  5. 75 FR 54492 - Oral Dosage Form New Animal Drugs; Tiamulin

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-08

    ... HUMAN SERVICES Food and Drug Administration 21 CFR Part 520 Oral Dosage Form New Animal Drugs; Tiamulin... (FDA) is amending the animal drug regulations to reflect approval of a supplemental new animal drug application (NADA) filed by Novartis Animal Health US, Inc. The supplemental NADA provides for use of...

  6. 76 FR 38554 - Oral Dosage Form New Animal Drugs; Amprolium

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-01

    ... HUMAN SERVICES Food and Drug Administration 21 CFR Part 520 Oral Dosage Form New Animal Drugs; Amprolium... (FDA) is amending the animal drug regulations to reflect approval of an original abbreviated new animal... requirements in 5 U.S.C. 801-808. List of Subjects in 21 CFR Part 520 Animal drugs. Therefore, under...

  7. 76 FR 78815 - Oral Dosage Form New Animal Drugs; Cyclosporine

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-20

    ... HUMAN SERVICES Food and Drug Administration 21 CFR Part 520 Oral Dosage Form New Animal Drugs... Administration (FDA) is amending the animal drug regulations to reflect approval of a new animal drug application (NADA) filed by Novartis Animal Health US, Inc. The NADA provides for the veterinary prescription use...

  8. Evaluation du niveau de connaissance des patients sur la gestion du traitement par les antis vitamines K dans le service de cardiologie de Ouagadougou

    PubMed Central

    Samadoulougou, André; Temoua Naibe, Dangwé; Mandi, Germain; Yameogo, Relwendé Aristide; Kabore, Elisé; Millogo, Georges; Yameogo, Nobila Valentin; Kologo, Jonas Koudougou; Thiam/Tall, Anna; Toguyeni, Boubacar Jean Yves; Zabsonre, Patrice

    2014-01-01

    Introduction Les antivitamines K (AVK), traitement anticoagulant oral le plus largement prescrit, posent un réel problème de santé publique du fait de leur risque iatrogène. L'objectif de cette étude était de préciser le niveau de connaissance des patients sur la gestion de leur traitement par les AVK. Méthodes Il s'est agi d'une enquête transversale descriptive réalisée au CHU-Yalgado Ouédraogo, sur une période de 03 mois : du 1er mars au 31 mai 2012. Un questionnaire a été administré aux patients bénéficiant d'un traitement AVK depuis au moins un mois. Résultats Soixante-dix patients ont été inclus dans l'étude dont 30 hommes. L'âge moyen était de 49 ans ± 16 ans. Les cardiopathies et la maladie thromboembolique veineuse justifiant l'institution du traitement AVK étaient retrouvées respectivement dans 58,6% et 41,4% des cas. Le nom de l'AVK et la raison exacte du traitement étaient connus respectivement dans 91,4% et 67,1% des cas. Plus de la moitié des patients (68,6%) savaient que les AVK rendaient le sang plus fluide. Quarante-six patients (65,7%) citaient l'INR comme examen biologique de surveillance du traitement et seulement 28 patients (40%) connaissaient les valeurs cibles. La majorité des patients ne connaissait pas les risques encourus en cas de surdosage (72,8%) et de sous-dosage (71,4%). Une automédication par anti-inflammatoire non stéroïdien était signalée par 18 patients (25,7%). Les choux (74,3%) et la laitue (62,9%), aliments à consommer avec modération, étaient les plus cités. Conclusion Les connaissances des patients sur la gestion des AVK étaient fragmentaires et insuffisantes pour assurer la sécurité et l'efficacité du traitement. La création d'un programme d'éducation thérapeutique sur les AVK s'avère alors nécessaire. PMID:25870741

  9. Modeling Effective Dosages in Hormetic Dose-Response Studies

    PubMed Central

    Belz, Regina G.; Piepho, Hans-Peter

    2012-01-01

    Background Two hormetic modifications of a monotonically decreasing log-logistic dose-response function are most often used to model stimulatory effects of low dosages of a toxicant in plant biology. As just one of these empirical models is yet properly parameterized to allow inference about quantities of interest, this study contributes the parameterized functions for the second hormetic model and compares the estimates of effective dosages between both models based on 23 hormetic data sets. Based on this, the impact on effective dosage estimations was evaluated, especially in case of a substantially inferior fit by one of the two models. Methodology/Principal Findings The data sets evaluated described the hormetic responses of four different test plant species exposed to 15 different chemical stressors in two different experimental dose-response test designs. Out of the 23 data sets, one could not be described by any of the two models, 14 could be better described by one of the two models, and eight could be equally described by both models. In cases of misspecification by any of the two models, the differences between effective dosages estimates (0–1768%) greatly exceeded the differences observed when both models provided a satisfactory fit (0–26%). This suggests that the conclusions drawn depending on the model used may diverge considerably when using an improper hormetic model especially regarding effective dosages quantifying hormesis. Conclusions/Significance The study showed that hormetic dose responses can take on many shapes and that this diversity can not be captured by a single model without risking considerable misinterpretation. However, the two empirical models considered in this paper together provide a powerful means to model, prove, and now also to quantify a wide range of hormetic responses by reparameterization. Despite this, they should not be applied uncritically, but after statistical and graphical assessment of their adequacy. PMID

  10. Approche de prise en charge du trouble du spectre de l’autisme

    PubMed Central

    Lee, Patrick F.; Thomas, Roger E.; Lee, Patricia A.

    2015-01-01

    Résumé Objectif Se pencher sur les critères diagnostiques du trouble du spectre de l’autisme (TSA) comme les définit le Manuel diagnostique et statistique des troubles mentaux, cinquième édition (DSM-V), et concevoir une approche de prise en charge du TSA à l’aide du cadre CanMEDS–Médecine familiale (CanMEDS-MF). Sources d’information Le DSM-V, publié par l’American Psychiatric Association en mai 2013, énonce de nouveaux critères diagnostiques du TSA. Le cadre CanMEDS-MF du Collège des médecins de famille du Canada fournit un plan d’orientation pour la prise en charge complexe du TSA. Nous avons utilisé des données recueillies par le Centers for Disease Control and Prevention afin de déterminer la prévalence du TSA, ainsi que la revue systématique et méta-analyse détaillée effectuée par le National Institute for Health and Care Excellence du R.-U. pour ses lignes directrices sur le TSA dans le but d’évaluer les données probantes issues de plus de 100 interventions. Message principal Selon les données du Centers for Disease Control and Prevention, la prévalence du TSA se chiffrait à 1 sur 88 en 2008 aux États-Unis. La classification du TSA dans la quatrième édition du DSM incluait l’autisme, le syndrome d’Asperger, le trouble envahissant du développement et le trouble désintégratif de l’enfance. La dernière révision du DSM-V réunit tous ces troubles sous la mention TSA, avec différents niveaux de sévérité. La prise en charge du TSA est complexe; elle exige les efforts d’une équipe multidisciplinaire ainsi que des soins continus. Les rôles CanMEDS-MF fournissent un cadre de prise en charge. Conclusion Les médecins de famille sont au cœur de l’équipe de soins multidisciplinaire pour le TSA, et le cadre CanMEDS-MF tient lieu de plan détaillé pour guider la prise en charge d’un enfant atteint de TSA et aider la famille de cet enfant.

  11. 1p36 tumor suppression--a matter of dosage?

    PubMed

    Henrich, Kai-Oliver; Schwab, Manfred; Westermann, Frank

    2012-12-01

    A broad range of human malignancies is associated with nonrandom 1p36 deletions, suggesting the existence of tumor suppressors encoded in this region. Evidence for tumor-specific inactivation of 1p36 genes in the classic "two-hit" manner is scarce; however, many tumor suppressors do not require complete inactivation but contribute to tumorigenesis by partial impairment. We discuss recent data derived from both human tumors and functional cancer models indicating that the 1p36 genes CHD5, CAMTA1, KIF1B, CASZ1, and miR-34a contribute to cancer development when reduced in dosage by genomic copy number loss or other mechanisms. We explore potential interactions among these candidates and propose a model where heterozygous 1p36 deletion impairs oncosuppressive pathways via simultaneous downregulation of several dosage-dependent tumor suppressor genes.

  12. Terminology challenges: defining modified release dosage forms in veterinary medicine.

    PubMed

    Martinez, Marilyn N; Lindquist, Danielle; Modric, Sanja

    2010-08-01

    Terminologies for describing dosage form release characteristics for human pharmaceuticals have been addressed by bodies such as the US Food and Drug Administration (FDA), the International Conference on Harmonization (ICH), and the US Pharmacopeia (USP). While the definition for terms such as "immediate release," "modified release," "extended release," and "delayed release" are now well accepted for human pharmaceuticals, confusion still exists within the veterinary community. In part, this confusion is attributable to differences between human and veterinary dosage forms (such as the preponderance of parenteral vs. oral extended release products for use in animals vs. the focus on oral extended release formulations for human use) which reflect interspecies differences in physiology and conditions of use. It also simply reflects a lack of attention to existing definitions. In an effort to remedy this problem, this manuscript reflects an initial effort to suggest definitions that may be appropriate for describing formulation effects in veterinary medicine.

  13. Regulatory perspectives on acceptability testing of dosage forms in children.

    PubMed

    Kozarewicz, Piotr

    2014-08-05

    Current knowledge about the age-appropriateness of different dosage forms is still fragmented or limited. Applicants are asked to demonstrate that the target age group(s) can manage the dosage form or propose an alternative strategy. However, questions remain about how far the applicant must go and what percentage of patients must find the strategy 'acceptable'. The aim of this overview is to provide an update on current thinking and understanding of the problem, and discuss issues relating to the acceptability testing. This overview should be considered as means to start a wider discussion which hopefully will result in a harmonised, globally acceptable approach for confirmation of the acceptability in the future.

  14. Biowaiver monographs for immediate release solid oral dosage forms: prednisone.

    PubMed

    Vogt, M; Derendorf, H; Krämer, J; Junginger, H E; Midha, K K; Shah, V P; Stavchansky, S; Dressman, J B; Barends, D M

    2007-06-01

    Literature data relevant to the decision to allow a waiver of in vivo bioequivalence (BE) testing for the approval of immediate release (IR) solid oral dosage forms containing prednisone are reviewed. Due to insufficient data prednisone cannot be definitively classified according to the current Biopharmaceutics Classification System (BCS) criteria as both the solubility and the permeability of prednisone are on the borderline of the present criteria of BCS Class I. Prednisone's therapeutic indications and therapeutic index, pharmacokinetics and the possibility of excipient interactions were also taken into consideration. Available evidence indicates that a biowaiver for IR solid oral dosage forms formulated with the excipients tabulated in this article would be unlikely to expose patients to undue risks.

  15. RFID Tag Helix Antenna Sensors for Wireless Drug Dosage Monitoring.

    PubMed

    Huang, Haiyu; Zhao, Peisen; Chen, Pai-Yen; Ren, Yong; Liu, Xuewu; Ferrari, Mauro; Hu, Ye; Akinwande, Deji

    2014-01-01

    Miniaturized helix antennas are integrated with drug reservoirs to function as RFID wireless tag sensors for real-time drug dosage monitoring. The general design procedure of this type of biomedical antenna sensors is proposed based on electromagnetic theory and finite element simulation. A cost effective fabrication process is utilized to encapsulate the antenna sensor within a biocompatible package layer using PDMS material, and at the same time form a drug storage or drug delivery unit inside the sensor. The in vitro experiment on two prototypes of antenna sensor-drug reservoir assembly have shown the ability to monitor the drug dosage by tracking antenna resonant frequency shift from 2.4-2.5-GHz ISM band with realized sensitivity of 1.27 [Formula: see text] for transdermal drug delivery monitoring and 2.76-[Formula: see text] sensitivity for implanted drug delivery monitoring.

  16. Six3 dosage mediates the pathogenesis of holoprosencephaly.

    PubMed

    Geng, Xin; Acosta, Sandra; Lagutin, Oleg; Gil, Hyea Jin; Oliver, Guillermo

    2016-12-01

    Holoprosencephaly (HPE) is defined as the incomplete separation of the two cerebral hemispheres. The pathology of HPE is variable and, based on the severity of the defect, HPE is divided into alobar, semilobar, and lobar. Using a novel hypomorphic Six3 allele, we demonstrate in mice that variability in Six3 dosage results in different HPE phenotypes. Furthermore, we show that whereas the semilobar phenotype results from severe downregulation of Shh expression in the rostral diencephalon ventral midline, the alobar phenotype is caused by downregulation of Foxg1 expression in the anterior neural ectoderm. Consistent with these results, in vivo activation of the Shh signaling pathway rescued the semilobar phenotype but not the alobar phenotype. Our findings show that variations in Six3 dosage result in different forms of HPE.

  17. Practical issues of hyperspectral imaging analysis of solid dosage forms.

    PubMed

    Amigo, José Manuel

    2010-09-01

    Hyperspectral imaging techniques have widely demonstrated their usefulness in different areas of interest in pharmaceutical research during the last decade. In particular, middle infrared, near infrared, and Raman methods have gained special relevance. This rapid increase has been promoted by the capability of hyperspectral techniques to provide robust and reliable chemical and spatial information on the distribution of components in pharmaceutical solid dosage forms. Furthermore, the valuable combination of hyperspectral imaging devices with adequate data processing techniques offers the perfect landscape for developing new methods for scanning and analyzing surfaces. Nevertheless, the instrumentation and subsequent data analysis are not exempt from issues that must be thoughtfully considered. This paper describes and discusses the main advantages and drawbacks of the measurements and data analysis of hyperspectral imaging techniques in the development of solid dosage forms.

  18. Global analysis of X-chromosome dosage compensation

    PubMed Central

    Gupta, Vaijayanti; Parisi, Michael; Sturgill, David; Nuttall, Rachel; Doctolero, Michael; Dudko, Olga K; Malley, James D; Eastman, P Scott; Oliver, Brian

    2006-01-01

    Background Drosophila melanogaster females have two X chromosomes and two autosome sets (XX;AA), while males have a single X chromosome and two autosome sets (X;AA). Drosophila male somatic cells compensate for a single copy of the X chromosome by deploying male-specific-lethal (MSL) complexes that increase transcription from the X chromosome. Male germ cells lack MSL complexes, indicating that either germline X-chromosome dosage compensation is MSL-independent, or that germ cells do not carry out dosage compensation. Results To investigate whether dosage compensation occurs in germ cells, we directly assayed X-chromosome transcripts using DNA microarrays and show equivalent expression in XX;AA and X;AA germline tissues. In X;AA germ cells, expression from the single X chromosome is about twice that of a single autosome. This mechanism ensures balanced X-chromosome expression between the sexes and, more importantly, it ensures balanced expression between the single X chromosome and the autosome set. Oddly, the inactivation of an X chromosome in mammalian females reduces the effective X-chromosome dose and means that females face the same X-chromosome transcript deficiency as males. Contrary to most current dosage-compensation models, we also show increased X-chromosome expression in X;AA and XX;AA somatic cells of Caenorhabditis elegans and mice. Conclusion Drosophila germ cells compensate for X-chromosome dose. This occurs by equilibrating X-chromosome and autosome expression in X;AA cells. Increased expression of the X chromosome in X;AA individuals appears to be phylogenetically conserved. PMID:16507155

  19. Les plaies du tendon patellaire

    PubMed Central

    Mechchat, Atif; Elidrissi, Mohammed; Mardy, Abdelhak; Elayoubi, Abdelghni; Shimi, Mohammed; Elibrahimi, Abdelhalim; Elmrini, Abdelmajid

    2014-01-01

    Les plaies du tendon patellaire sont peu fréquentes et sont peu rapportés dans la littérature, contrairement aux ruptures sous cutanées. Les sections du tendon patellaire nécessitent une réparation immédiate afin de rétablir l'appareil extenseur et de permettre une récupération fonctionnelle précoce. A travers ce travail rétrospectif sur 13 cas, nous analysons les aspects épidémiologiques, thérapeutiques et pronostiques de ce type de pathologie en comparant différents scores. L’âge moyen est de 25 ans avec une prédominance masculine. Les étiologies sont dominées par les accidents de la voie publique (68%) et les agressions par agent tranchant (26%) et contendant (6 %). Tous nos patients ont bénéficié d'un parage chirurgical avec suture tendineuse direct protégée par un laçage au fils d'aciers en légère flexion. La rééducation est débutée après sédation des phénomènes inflammatoires. Au dernier recul les résultats sont excellents et bon à 92%. Nous n'avons pas noté de différence de force musculaire et d'amplitude articulaire entre le genou sain et le genou lésé. Les lésions ouvertes du tendon patellaire est relativement rare. La prise en charge chirurgicale rapide donne des résultats assez satisfaisants. La réparation est généralement renforcée par un semi-tendineux, synthétique ou métallique en forme de cadre de renfort pour faciliter la réadaptation et réduire le risque de récidive après la fin de l'immobilisation. PMID:25170379

  20. Dosage Compensation in the African Malaria Mosquito Anopheles gambiae

    PubMed Central

    Rose, Graham; Krzywinska, Elzbieta; Kim, Jan; Revuelta, Loic; Ferretti, Luca; Krzywinski, Jaroslaw

    2016-01-01

    Dosage compensation is the fundamental process by which gene expression from the male monosomic X chromosome and from the diploid set of autosomes is equalized. Various molecular mechanisms have evolved in different organisms to achieve this task. In Drosophila, genes on the male X chromosome are upregulated to the levels of expression from the two X chromosomes in females. To test whether a similar mechanism is operating in immature stages of Anopheles mosquitoes, we analyzed global gene expression in the Anopheles gambiae fourth instar larvae and pupae using high-coverage RNA-seq data. In pupae of both sexes, the median expression ratios of X-linked to autosomal genes (X:A) were close to 1.0, and within the ranges of expression ratios between the autosomal pairs, consistent with complete compensation. Gene-by-gene comparisons of expression in males and females revealed mild female bias, likely attributable to a deficit of male-biased X-linked genes. In larvae, male to female ratios of the X chromosome expression levels were more female biased than in pupae, suggesting that compensation may not be complete. No compensation mechanism appears to operate in male germline of early pupae. Confirmation of the existence of dosage compensation in A. gambiae lays the foundation for research into the components of dosage compensation machinery in this important vector species. PMID:26782933

  1. Status of dosage compensation of X chromosome in bovine genome.

    PubMed

    Ka, Sojeong; Ahn, Hyeonju; Seo, Minseok; Kim, Heebal; Kim, Jin Nam; Lee, Hyun-Jeong

    2016-08-01

    Dosage compensation system with X chromosome upregulation and inactivation have evolved to overcome the genetic imbalance between sex chromosomes in both male and female of mammals. Although recent development of chromosome-wide technologies has allowed us to test X upregulation, discrete data processing and analysis methods draw disparate conclusions. A series of expression studies revealed status of dosage compensation in some species belonging to monotremes, marsupials, rodents and primates. However, X upregulation in the Artiodactyla order including cattle have not been studied yet. In this study, we surveyed the genome-wide transcriptional upregulation in X chromosome in cattle RNA-seq data using different gene filtration methods. Overall examination of RNA-seq data revealed that X chromosome in the pituitary gland expressed more genes than in other peripheral tissues, which was consistent with the previous results observed in human and mouse. When analyzed with globally expressed genes, a median X:A expression ratio was 0.94. The ratio of 1-to-1 ortholog genes between chicken and mammals, however, showed considerable reduction to 0.68. These results indicate that status of dosage compensation for cattle is not deviated from those found in rodents and primate, and this is consistent with the evolutionary history of cattle.

  2. Biowaiver monographs for immediate release solid oral dosage forms: rifampicin.

    PubMed

    Becker, C; Dressman, J B; Junginger, H E; Kopp, S; Midha, K K; Shah, V P; Stavchansky, S; Barends, D M

    2009-07-01

    Literature data relevant to the decision to allow a waiver of in vivo bioequivalence (BE) testing for the approval of new multisource and reformulated immediate release (IR) solid oral dosage forms containing rifampicin as the only Active Pharmaceutical Ingredient (API) are reviewed. Rifampicin's solubility and permeability, its therapeutic use and index, pharmacokinetics, excipient interactions and reported BE/bioavailability (BA) problems were taken into consideration. Solubility and absolute BA data indicate that rifampicin is a BCS Class II drug. Of special concern for biowaiving is that many reports of failure of IR solid oral dosage forms of rifampicin to meet BE have been published and the reasons for these failures are yet insufficiently understood. Moreover, no reports were identified in which in vitro dissolution was shown to be predictive of nonequivalence among products. Therefore, a biowaiver based approval of rifampicin containing IR solid oral dosage forms cannot be recommended for either new multisource drug products or for major scale-up and postapproval changes (variations) to existing drug products.

  3. Biowaiver monographs for immediate release solid oral dosage forms: pyrazinamide.

    PubMed

    Becker, C; Dressman, J B; Amidon, G L; Junginger, H E; Kopp, S; Midha, K K; Shah, V P; Stavchansky, S; Barends, D M

    2008-09-01

    Literature data relevant to the decision to allow a waiver of in vivo bioequivalence (BE) testing for the approval of immediate release (IR) solid oral dosage forms containing pyrazinamide as the only active pharmaceutical ingredient (API) are reviewed. Pyrazinamide is BCS Class III, with linear absorption over a wide dosing range. The risk of bioinequivalence is estimated to be low. Depending on the definition used, pyrazinamide can be classified as a narrow therapeutic index (NTI) drug, which is usually a caveat to biowaiving but may be deemed acceptable if the Summary of Product Characteristics (SmPCs) of the test product stipulates the need for regular monitoring of liver function. It is concluded that a biowaiver can be recommended for IR solid oral dosage only when the test product (a) contains only excipients present in pyrazinamide IR solid oral drug products approved in ICH or associated countries, (b) these excipients are present in amounts normally used in IR solid oral dosage forms, (c) the test product is very rapidly dissolving, (d) the SmPC of the test product indicates the need for monitoring of the patient's liver function.

  4. Biowaiver Monographs for Immediate Release Solid Oral Dosage Forms: Levetiracetam.

    PubMed

    Petruševska, Marija; Berglez, Sandra; Krisch, Igor; Legen, Igor; Megušar, Klara; Peternel, Luka; Abrahamsson, Bertil; Cristofoletti, Rodrigo; Groot, D W; Kopp, Sabine; Langguth, Peter; Mehta, Mehul; Polli, James E; Shah, Vinod P; Dressman, Jennifer

    2015-09-01

    Literature and experimental data relevant for the decision to allow a waiver of in vivo bioequivalence (BE) testing for the approval of immediate release (IR) solid oral dosage forms containing levetiracetam are reviewed. Data on solubility and permeability suggest that levetiracetam belongs to class I of the biopharmaceutical classification system (BCS). Levetiracetam's therapeutic use, its wide therapeutic index, and its favorable pharmacokinetic properties make levetiracetam a valid candidate for the BCS-based biowaiver approach. Further, no BE studies with levetiracetam IR formulations in which the test formulation failed to show BE with the comparator have been reported in the open literature. On the basis of the overall evidence, it appears unlikely that a BCS-based biowaiver approach for levetiracetam IR solid oral dosage forms formulated with established excipients would expose patients to undue risks. Thus, the BCS-based biowaiver approach procedure is recommended for IR solid oral dosage form containing levetiracetam, provided the excipients in the formulation are also present in products that have been approved in countries belonging to or associated with the International Committee on Harmonization and are used in their usual quantities, and provided the dissolution profiles of the test and reference product comply with the current requirements for BCS-based biowaivers.

  5. Gastric emptying of multi-particulate dosage forms.

    PubMed

    Newton, J Michael

    2010-08-16

    The evidence in the literature for the concept that multi-particulate dosage forms below a specific size empty from the stomach as if they were liquids and hence have the potential to provide the best solution to the formulation of controlled release oral dosage forms, has been considered. There is some evidence that particles less than 1.0mm provide a more rapid response than larger size particles but there is also evidence that this is not always the case and that rapid and reproducible gastric emptying of small particles does not always occur when they are administered. There is strong evidence that food can delay the gastric emptying of multi-particulate systems. Some of the misconception for gastric emptying performance of multi-particulate system is shown to be related to the limitation of the study design and limitation of the way the data is processed. Nevertheless, there is clear evidence that multi-particulate systems can provide effective oral controlled release dosage forms. There is still some way to go with experimental techniques which would allow a definitive answer to the issue of how the variability of the gastric emptying of multi-particulate systems of less than 2.0mm arises.

  6. Spectrophotometric Assay of Mebendazole in Dosage Forms Using Sodium Hypochlorite

    NASA Astrophysics Data System (ADS)

    Swamy, N.; Prashanth, K. N.; Basavaiah, K.

    2014-07-01

    A simple, selective and sensitive spectrophotometric method is described for the determination of mebendazole (MBD) in bulk drug and dosage forms. The method is based on the reaction of MBD with hypochlorite in the presence of sodium bicarbonate to form the chloro derivative of MBD, followed by the destruction of the excess hypochlorite by nitrite ion. The color was formed by the oxidation of iodide with the chloro derivative of MBD to iodine in the presence of starch and forming the blue colored product, which was measured at 570 nm. The optimum conditions that affect the reaction were ascertained and, under these conditions, a linear relationship was obtained in the concentration range of 1.25-25.0·g/ml MBD. The calculated molar absorptivity and Sandell sensitivity values are 9.56·103 l·mol-1·cm-1 and 0.031 μg/cm2, respectively. The limits of detection and quantification are 0.11 and 0.33 μg/ml, respectively. The proposed method was applied successfully to the determination of MBD in bulk drug and dosage forms, and no interference was observed from excipients present in the dosage forms. The reliability of the proposed method was further checked by parallel determination by the reference method and also by recovery studies.

  7. Biopharmaceutical considerations and characterizations in development of colon targeted dosage forms for inflammatory bowel disease.

    PubMed

    Malayandi, Rajkumar; Kondamudi, Phani Krishna; Ruby, P K; Aggarwal, Deepika

    2014-04-01

    Colon targeted dosage forms have been extensively studied for the localized treatment of inflammatory bowel disease. These dosage forms not only improve the therapeutic efficacy but also reduce the incidence of adverse drug reactions and hence improve the patient compliance. However, complex and highly variable gastro intestinal physiology limits the clinical success of these dosage forms. Biopharmaceutical characteristics of these dosage forms play a key role in rapid formulation development and ensure the clinical success. The complexity in product development and clinical success of colon targeted dosage forms are based on the biopharmaceutical characteristics such as physicochemical properties of drug substances, pharmaceutical characteristics of dosage form, physiological conditions and pharmacokinetic properties of drug substances as well as drug products. Various in vitro and in vivo techniques have been employed in past to characterize the biopharmaceutical properties of colon targeted dosage forms. This review focuses on the factors influencing the biopharmaceutical performances of the dosage forms, in vitro characterization techniques and in vivo studies.

  8. 21 CFR 520.1263 - Lincomycin hydrochloride monohydrate oral dosage forms.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Lincomycin hydrochloride monohydrate oral dosage... HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.1263 Lincomycin hydrochloride monohydrate oral dosage forms....

  9. 21 CFR 520.1326 - Mebendazole and trichlorfon oral dosage forms.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Mebendazole and trichlorfon oral dosage forms. 520... SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.1326 Mebendazole and trichlorfon oral dosage forms....

  10. 21 CFR 524.390 - Chloramphenicol ophthalmic and topical dosage forms.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Chloramphenicol ophthalmic and topical dosage... HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS OPHTHALMIC AND TOPICAL DOSAGE FORM NEW ANIMAL DRUGS § 524.390 Chloramphenicol ophthalmic and topical dosage forms....

  11. 21 CFR 520.2158 - Streptomycin/dihydrostreptomycin oral dosage forms.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Streptomycin/dihydrostreptomycin oral dosage forms... SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.2158 Streptomycin/dihydrostreptomycin oral dosage forms....

  12. 21 CFR 522.1696 - Penicillin G procaine implantation and injectable dosage forms.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Penicillin G procaine implantation and injectable dosage forms. 522.1696 Section 522.1696 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH... DOSAGE FORM NEW ANIMAL DRUGS § 522.1696 Penicillin G procaine implantation and injectable dosage forms....

  13. 21 CFR 522.1696 - Penicillin G procaine implantation and injectable dosage forms.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Penicillin G procaine implantation and injectable dosage forms. 522.1696 Section 522.1696 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH... DOSAGE FORM NEW ANIMAL DRUGS § 522.1696 Penicillin G procaine implantation and injectable dosage forms....

  14. 21 CFR 522.1696 - Penicillin G procaine implantation and injectable dosage forms.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Penicillin G procaine implantation and injectable dosage forms. 522.1696 Section 522.1696 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH... DOSAGE FORM NEW ANIMAL DRUGS § 522.1696 Penicillin G procaine implantation and injectable dosage forms....

  15. 21 CFR 522.1696 - Penicillin G procaine implantation and injectable dosage forms.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Penicillin G procaine implantation and injectable dosage forms. 522.1696 Section 522.1696 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH... DOSAGE FORM NEW ANIMAL DRUGS § 522.1696 Penicillin G procaine implantation and injectable dosage forms....

  16. 21 CFR 330.3 - Imprinting of solid oral dosage form drug products.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 5 2011-04-01 2011-04-01 false Imprinting of solid oral dosage form drug products... AS SAFE AND EFFECTIVE AND NOT MISBRANDED General Provisions § 330.3 Imprinting of solid oral dosage form drug products. A requirement to imprint an identification code on solid oral dosage form...

  17. 21 CFR 330.3 - Imprinting of solid oral dosage form drug products.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Imprinting of solid oral dosage form drug products... AS SAFE AND EFFECTIVE AND NOT MISBRANDED General Provisions § 330.3 Imprinting of solid oral dosage form drug products. A requirement to imprint an identification code on solid oral dosage form...

  18. The Development of Teaching Efficacy for Drug-Dosage Calculation Instruction: A Nursing Faculty Perspective

    ERIC Educational Resources Information Center

    Vitale, Gail A.

    2011-01-01

    The purpose of this study was to examine how nursing efficacy for drug-dosage calculation instruction is determined. Medication administration is a critical function of nurses in healthcare settings. An essential component of safe medication administration is accurate drug-dosage calculation, but instruction in drug-dosage calculation methods…

  19. 21 CFR 522.960 - Flumethasone implantation or injectable dosage forms.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Flumethasone implantation or injectable dosage... HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.960 Flumethasone implantation or injectable dosage forms....

  20. 21 CFR 522.960 - Flumethasone implantation or injectable dosage forms.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Flumethasone implantation or injectable dosage... HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.960 Flumethasone implantation or injectable dosage forms....

  1. 21 CFR 522.960 - Flumethasone implantation or injectable dosage forms.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Flumethasone implantation or injectable dosage... HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.960 Flumethasone implantation or injectable dosage forms....

  2. 21 CFR 522.960 - Flumethasone implantation or injectable dosage forms.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Flumethasone implantation or injectable dosage... HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.960 Flumethasone implantation or injectable dosage forms....

  3. Learning about Cri du Chat Syndrome

    MedlinePlus

    ... chat syndrome - also known as 5p- syndrome and cat cry syndrome - is a rare genetic condition that ... du chat syndrome usually include a high-pitched cat-like cry, mental retardation, delayed development, distinctive facial ...

  4. 76 FR 63304 - Guidance for Industry on Incorporation of Physical-Chemical Identifiers Into Solid Oral Dosage...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-10-12

    ... Solid Oral Dosage Form Drug Products for Anticounterfeiting; Availability AGENCY: Food and Drug... Oral Dosage Form Drug Products for Anticounterfeiting.'' This guidance provides recommendations on... Identifiers Into Solid Oral Dosage Form Drug Products for Anticounterfeiting.'' For the purpose of...

  5. Neutron and Proton Dosages in the Upper Atmosphere from Solar Flare Radiation.

    PubMed

    Flamm, E J; Lingenfelter, R E

    1964-06-26

    The radiation dosage from secondary neutrons as well as from primary and secondary protons in the earth's atmosphere during solar particle events is calculated as a function of the solar proton flux, atmospheric depth, and geomagnetic-cutoff rigidity. The dosage in rems from secondary neutrons exceeds the dosage from protons below 30 g/cm(2) of residual atmosphere. Neutron dosages in rads are less than the dosage from primary protons at all depths above 100 g/cm(2). The maximum neutron dose to travelers in supersonic aircraft during solar particle events of the magnitude observed during the last solar cycle would be of the order of I rem.

  6. Drug dosage recommendations in patients with chronic liver disease.

    PubMed

    Periáñez-Párraga, Leonor; Martínez-López, Iciar; Ventayol-Bosch, Pere; Puigventós-Latorre, Francesc; Delgado-Sánchez, Olga

    2012-04-01

    Chronic liver diseases (CLD) alter the kinetics of drugs. Despite dosage adjustment is based on Child-Pugh scores, there are no available recommendations and/or algorithms of reference to facilitate dosage regimens. A literature review about dose adjustment of the drugs from the hospital guide -which are included in the list of the WHO recommended drugs to be avoided or used with caution in patients with liver disease- was carried out. The therapeutic novelties from the last few years were also included. In order to do so, the summary of product characteristics (SPC), the database DrugDex-Micromedex, the WHO recommendations and the review articles from the last 10 years in Medline were reviewed. Moreover, the kinetic parameters of each drug were calculated with the aim of establishing a theoretical recommendation based on the proposal of Delcò and Huet. Recommendations for 186 drugs are presented according to the SPC (49.5%), DrugDex-Micromedex (26.3%) and WHO (18.8%) indications; six recommendations were based on specific publications; the theoretical recommendation based on pharmacokinetic parameters was proposed in four drugs. The final recommendations for clinical management were: dosage modification (26.9%), hepatic/analytical monitoring of the patient (8.6%), contraindication (18.8%), use with caution (19.3%) and no adjustment required (26.3%). In this review, specific recommendations for the practical management of patients with chronic liver disease are presented. It has been elaborated through a synthesis of the published bibliography and completed by following a theoretical methodology.

  7. Gene Expression Dosage Regulation in an Allopolyploid Fish

    PubMed Central

    Matos, I; Machado, M. P.; Schartl, M.; Coelho, M. M.

    2015-01-01

    How allopolyploids are able not only to cope but profit from their condition is a question that remains elusive, but is of great importance within the context of successful allopolyploid evolution. One outstanding example of successful allopolyploidy is the endemic Iberian cyprinid Squalius alburnoides. Previously, based on the evaluation of a few genes, it was reported that the transcription levels between diploid and triploid S. alburnoides were similar. If this phenomenon occurs on a full genomic scale, a wide functional ‘‘diploidization’’ could be related to the success of these polyploids. We generated RNA-seq data from whole juvenile fish and from adult livers, to perform the first comparative quantitative transcriptomic analysis between diploid and triploid individuals of a vertebrate allopolyploid. Together with an assay to estimate relative expression per cell, it was possible to infer the relative sizes of transcriptomes. This showed that diploid and triploid S. alburnoides hybrids have similar liver transcriptome sizes. This in turn made it valid to directly compare the S. alburnoides RNA-seq transcript data sets and obtain a profile of dosage responses across the S. alburnoides transcriptome. We found that 64% of transcripts in juveniles’ samples and 44% in liver samples differed less than twofold between diploid and triploid hybrids (similar expression). Yet, respectively 29% and 15% of transcripts presented accurate dosage compensation (PAA/PA expression ratio of 1 instead of 1.5). Therefore, an exact functional diploidization of the triploid genome does not occur, but a significant down regulation of gene expression in triploids was observed. However, for those genes with similar expression levels between diploids and triploids, expression is not globally strictly proportional to gene dosage nor is it set to a perfect diploid level. This quantitative expression flexibility may be a strong contributor to overcome the genomic shock, and be an

  8. On p53 revival using system oriented drug dosage design.

    PubMed

    Haseeb, Muhammad; Azam, Shumaila; Bhatti, A I; Azam, Rizwan; Ullah, Mukhtar; Fazal, Sahar

    2017-02-21

    We propose a new paradigm in the drug design for the revival of the p53 pathway in cancer cells. It is shown that the current strategy of using small molecule based Mdm2 inhibitors is not enough to adequately revive p53 in cancerous cells, especially when it comes to the extracting pulsating behavior of p53. This fact has come to notice when a novel method for the drug dosage design is introduced using system oriented concepts. As a test case, small molecule drug Mdm2 repressor Nutlin 3a is considered. The proposed method determines the dose of Nutlin to revive p53 pathway functionality. For this purpose, PBK dynamics of Nutlin have also been integrated with p53 pathway model. The p53 pathway is the focus of researchers for the last thirty years for its pivotal role as a frontline cancer suppressant protein due to its effect on cell cycle checkpoints and cell apoptosis in response to a DNA strand break. That is the reason for finding p53 being absent in more than 50% of tumor cancers. Various drugs have been proposed to revive p53 in cancer cells. Small molecule based drugs are at the foremost and are the subject of advanced clinical trials. The dosage design of these drugs is an important issue. We use control systems concepts to develop the drug dosage so that the cancer cells can be treated in appropriate time. We investigate by using a computational model how p53 protein responds to drug Nutlin 3a, an agent that interferes with the MDM2-mediated p53 regulation. The proposed integrated model describes in some detail the regulation network of p53 including the negative feedback loop mediated by MDM2 and the positive feedback loop mediated by Mdm2 mRNA as well as the reversible represses of MDM2 caused by Nutlin. The reported PBK dynamics of Nutlin 3a are also incorporated to see the full effect. It has been reported that p53 response to stresses in two ways. Either it has a sustained (constant) p53 response, or there are oscillations in p53 concentration. The

  9. Relative bioavailability of scopolamine dosage forms and interaction with dextroamphetamine.

    PubMed

    Boyd, Jason L; Du, Brian; Vaksman, Zalman; Locke, James P; Putcha, Lakshmi

    2007-07-01

    The NASA Reduced Gravity Office (RGO) uses scopolamine (SCOP) alone and in combination with dextoamphetamine (DEX) to treat motion sickness symptoms during DC-9 parabolic flights. The medications are sometimes dispensed as custom dosage forms in gelatin capsules for convenience. Reports of treatment failure during flights by the flight surgeons suggest that these formulations may be less efficacious for the treatment of motion sickness due to unreliable and inadequate bioavailability. We estimated bioavailability of four different oral formulations used by the NASA RGO physicians for the treatment of motion sickness.

  10. Comprehensive review on additives of topical dosage forms for drug delivery.

    PubMed

    Garg, Tarun; Rath, Goutam; Goyal, Amit K

    2015-12-01

    Skin is the largest organ of the human body and plays the most important role in protecting against pathogen and foreign matter. Three important modes such as topical, regional and transdermal are widely used for delivery of various dosage forms. Among these modes, the topical dosage forms are preferred because it provides local therapeutic activity when applied to the skin or mucous membranes. Additives or pharmaceutical excipients (non-drug component of dosage form) are used as inactive ingredients in dosage form or tools for structuring dosage forms. The main use of topical dosage form additives are controling the extent of absorption, maintaining the viscosity, improving the stability as well as organoleptic property and increasing the bulk of the formulation. The overall goal of this article is to provide the clinician with information related to the topical dosage form additives and their current major applications against various diseases.

  11. Biokinetics and dosimetry of depleted uranium (DU) in rats implanted with DU fragments.

    SciTech Connect

    Guilmette, Ray A.; Hahn, Fletcher F.; Durbin, P. W.

    2004-01-01

    A number of U. S. veterans of the Persian Gulf War were wounded with depleted uranium (DU) metal fragments as a result of 'friendly fire' incidents, in which Abrams tanks and Bradley fighting vehicles were struck by DU anti-armor munitions. Some of the crew members who survived were left with multiple small fragments of DU in their muscles and soft tissues. The number, size and location of the fragments made them inoperable in general, and therefore subject to long-term retention. Because there was inadequate data to predict the potential carcinogenicity of DU fragments in soft tissues, Hahn et al. (2003) conducted a lifespan cancer study in rats. As part of that study, a number of rats were maintained to study the biokinetics and dosimetry of DU implanted intramuscularly in male Wistar rats. Typically, four metal fragments, either as cylindrical pellets or square wafers were implanted into the biceps femoris muscles of the rats. Urine samples were collected periodically during their lifespans, and DU was analyzed in kidneys and eviscerated carcass (minus the implant sites) at death. The daily DU urinary excretion rate increased steeply during the first 30 d after implantation peaking at about 90 d at 3-10 x 10{sup -3}%/d. During the first 150 d, the average excretion rate was 2.4 x 10{sup -3}%/d, decreasing thereafter to about 1 x 10{sup -3}%/d. Serial radiographs were made of the wound sites to monitor gross morphologic changes in the DU implant and the surrounding tissue. As early as 1 w after implantation, radiographs showed the presence of surface corrosion and small, dense bodies near the original implant, presumably DU. This corrosion from the surface of the implant continued with time, but did not result in an increasing amount of DU reaching the blood and urine after the first 3 mo. During this 3-mo period, connective tissue capsules formed around the implants, and are hypothesized to have reduced the access of DU to tissue fluids by limiting the diffusion

  12. Indications, usage, and dosage of the transfer factor.

    PubMed

    Berrón-Pérez, Renato; Chávez-Sánchez, Raúl; Estrada-García, Iris; Espinosa-Padilla, Sara; Cortez-Gómez, Rudyard; Serrano-Miranda, Ernestina; Ondarza-Aguilera, Rodolfo; Pérez-Tapia, Mayra; Pineda Olvera, Benjamín; Jiménez-Martínez, María del Carmen; Portugués, Abraham; Rodríguez, Azucena; Cano, Laura; Pacheco, Pedro Urcino; Barrientos, Javier; Chacón, Rommel; Serafín, Jeannet; Mendez, Patricia; Monges, Abelardo; Cervantes, Edgar; Estrada-Parra, Sergio

    2007-01-01

    The transfer factor (TF) was described in 1955 by S. Lawrence. In 1992 Kirkpatrick characterized the specific TF at molecular level. The TF is constituted by a group of numerous molecules, of low molecular weight, from 1.0 to 6.0 kDa. The 5 kDa fraction corresponds to the TF specific to antigens. There are a number of publications about the clinical indications of the TF for diverse diseases, in particular those where the cellular immune response is compromised or in those where there is a deficient regulation of the immune response. In this article we present our clinical and basic experiences, especially regarding the indications, usage and dosage of the TF. Our group demonstrated that the TF increases the expression of IFN-gamma and RANTES, while decreases the expression of osteopontine. Using animal models we have worked with M. tuberculosis, and with a model of glioma with good therapeutic results. In the clinical setting we have worked with herpes zoster, herpes simplex type I, herpetic keratitis, atopic dermatitis, osteosarcoma, tuberculosis, asthma, post-herpetic neuritis, anergic coccidioidomycosis, leishmaniasis, toxoplasmosis, mucocutaneous candidiasis, pediatric infections produced by diverse pathogen germs, sinusitis, pharyngitis, and otits media. All of these diseases were studied through protocols which main goals were to study the therapeutic effects of the TF, and to establish in a systematic way diverse dosage schema and time for treatment to guide the prescription of the TF.

  13. Comparative multiplex dosage analysis in spinocerebellar ataxia type 2 patients.

    PubMed

    Calì, F; Chiavetta, V; Ragalmuto, A; Vinci, M; Ruggeri, G; Schinocca, P; Romano, V

    2013-04-12

    We developed a new application of comparative multiplex dosage analysis (CMDA) for evaluation of the ataxin 2 gene. Expansions of the triplet CAG can cause spinocerebellar ataxia type 2 (SCA2), a neurodegenerative disease with an autosomal-dominant mode of inheritance. Molecular diagnosis of SCA2 is routinely based on the use of conventional PCR to detect the CAG expansion. However, PCR does not amplify an allele with an expansion of many triplets (>80), which is typically found in infantile and juvenile forms of SCA2, thus leading to false negatives. We propose the analysis of the ATXN2 gene by CMDA to complement existing methods currently used for the detection of large expansions of the CAG repeat. Using CMDA, the presence of any longer mutated allele in a heterozygous patient or fetus would be inferred due to dosage variation of the very frequent normal allele #22. CMDA can be completed in 1 day, at very low cost, and would be a useful tool for prenatal diagnosis and for diagnosis of presymptomatic forms of early-onset SCA2.

  14. X-Chromosome Dosage and the Response to Cerebral Ischemia

    PubMed Central

    Turtzo, L. Christine; Siegel, Chad; McCullough, Louise D.

    2011-01-01

    Gonadal hormones contribute to ischemic neuroprotection, but cannot fully explain the observed sexual dimorphism in stroke outcomes seen during life stages with low sex steroid hormones. Sex chromosomal complement (XX in females; XY in males) may also contribute to ischemic sexual dimorphism. A transient middle cerebral artery occlusion model was used to investigate the role of X chromosome dosage in female XX and XO littermates of two mouse strains (Paf and EdaTa). Cohorts of XX and XO gonadally intact, ovariectomized, and ovariectomized females supplemented with estrogen were examined. Infarct sizes were equivalent between ovariectomized XX and XO mice, between intact XX and XO mice, and between estrogen-supplemented ovariectomized XX and XO mice. This is the first study to investigate the role of sex chromosome dosage in the response to cerebral ischemia. Neither the number of X chromosomes, nor the parent of origin of the remaining X chromosome, had a significant effect on the degree of cerebral infarction after experimental stroke in adult female mice. Estrogen was protective against cerebral ischemia in both XX and XO mice. PMID:21917808

  15. RFID Tag Helix Antenna Sensors for Wireless Drug Dosage Monitoring

    PubMed Central

    Huang, Haiyu; Zhao, Peisen; Chen, Pai-Yen; Ren, Yong; Liu, Xuewu; Ferrari, Mauro; Hu, Ye; Akinwande, Deji

    2014-01-01

    Miniaturized helix antennas are integrated with drug reservoirs to function as RFID wireless tag sensors for real-time drug dosage monitoring. The general design procedure of this type of biomedical antenna sensors is proposed based on electromagnetic theory and finite element simulation. A cost effective fabrication process is utilized to encapsulate the antenna sensor within a biocompatible package layer using PDMS material, and at the same time form a drug storage or drug delivery unit inside the sensor. The in vitro experiment on two prototypes of antenna sensor-drug reservoir assembly have shown the ability to monitor the drug dosage by tracking antenna resonant frequency shift from 2.4–2.5-GHz ISM band with realized sensitivity of 1.27 \\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{upgreek} \\usepackage{mathrsfs} \\setlength{\\oddsidemargin}{-69pt} \\begin{document} }{}$\\mu~{\\rm l}/{\\rm MHz}$\\end{document} for transdermal drug delivery monitoring and 2.76-\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{upgreek} \\usepackage{mathrsfs} \\setlength{\\oddsidemargin}{-69pt} \\begin{document} }{}$\\mu~{\\rm l}/{\\rm MHz}$\\end{document} sensitivity for implanted drug delivery monitoring. PMID:27170865

  16. A genome wide dosage suppressor network reveals genomic robustness

    PubMed Central

    Patra, Biranchi; Kon, Yoshiko; Yadav, Gitanjali; Sevold, Anthony W.; Frumkin, Jesse P.; Vallabhajosyula, Ravishankar R.; Hintze, Arend; Østman, Bjørn; Schossau, Jory; Bhan, Ashish; Marzolf, Bruz; Tamashiro, Jenna K.; Kaur, Amardeep; Baliga, Nitin S.; Grayhack, Elizabeth J.; Adami, Christoph; Galas, David J.; Raval, Alpan; Phizicky, Eric M.; Ray, Animesh

    2017-01-01

    Genomic robustness is the extent to which an organism has evolved to withstand the effects of deleterious mutations. We explored the extent of genomic robustness in budding yeast by genome wide dosage suppressor analysis of 53 conditional lethal mutations in cell division cycle and RNA synthesis related genes, revealing 660 suppressor interactions of which 642 are novel. This collection has several distinctive features, including high co-occurrence of mutant-suppressor pairs within protein modules, highly correlated functions between the pairs and higher diversity of functions among the co-suppressors than previously observed. Dosage suppression of essential genes encoding RNA polymerase subunits and chromosome cohesion complex suggests a surprising degree of functional plasticity of macromolecular complexes, and the existence of numerous degenerate pathways for circumventing the effects of potentially lethal mutations. These results imply that organisms and cancer are likely able to exploit the genomic robustness properties, due the persistence of cryptic gene and pathway functions, to generate variation and adapt to selective pressures. PMID:27899637

  17. Emergence of 3D Printed Dosage Forms: Opportunities and Challenges.

    PubMed

    Alhnan, Mohamed A; Okwuosa, Tochukwu C; Sadia, Muzna; Wan, Ka-Wai; Ahmed, Waqar; Arafat, Basel

    2016-08-01

    The recent introduction of the first FDA approved 3D-printed drug has fuelled interest in 3D printing technology, which is set to revolutionize healthcare. Since its initial use, this rapid prototyping (RP) technology has evolved to such an extent that it is currently being used in a wide range of applications including in tissue engineering, dentistry, construction, automotive and aerospace. However, in the pharmaceutical industry this technology is still in its infancy and its potential yet to be fully explored. This paper presents various 3D printing technologies such as stereolithographic, powder based, selective laser sintering, fused deposition modelling and semi-solid extrusion 3D printing. It also provides a comprehensive review of previous attempts at using 3D printing technologies on the manufacturing dosage forms with a particular focus on oral tablets. Their advantages particularly with adaptability in the pharmaceutical field have been highlighted, which enables the preparation of dosage forms with complex designs and geometries, multiple actives and tailored release profiles. An insight into the technical challenges facing the different 3D printing technologies such as the formulation and processing parameters is provided. Light is also shed on the different regulatory challenges that need to be overcome for 3D printing to fulfil its real potential in the pharmaceutical industry.

  18. Ultraconserved Elements: Analyses of Dosage Sensitivity, Motifs and Boundaries

    PubMed Central

    Chiang, Charleston W. K.; Derti, Adnan; Schwartz, Daniel; Chou, Michael F.; Hirschhorn, Joel N.; Wu, C.-ting

    2008-01-01

    Ultraconserved elements (UCEs) are sequences that are identical between reference genomes of distantly related species. As they are under negative selection and enriched near or in specific classes of genes, one explanation for their ultraconservation may be their involvement in important functions. Indeed, many UCEs can drive tissue-specific gene expression. We have demonstrated that nonexonic UCEs are depleted among segmental duplications (SDs) and copy number variants (CNVs) and proposed that their ultraconservation may reflect a mechanism of copy counting via comparison. Here, we report that nonexonic UCEs are also depleted among 10 of 11 recent genomewide data sets of human CNVs, including 3 obtained with strategies permitting greater precision in determining the extents of CNVs. We further present observations suggesting that nonexonic UCEs per se may contribute to this depletion and that their apparent dosage sensitivity was in effect when they became fixed in the last common ancestor of mammals, birds, and reptiles, consistent with dosage sensitivity contributing to ultraconservation. Finally, in searching for the mechanism(s) underlying the function of nonexonic UCEs, we have found that they are enriched in TAATTA, which is also the recognition sequence for the homeodomain DNA-binding module, and bounded by a change in A + T frequency. PMID:18957701

  19. Genomic dosage effects on heterosis in triploid maize.

    PubMed

    Yao, Hong; Dogra Gray, Anjali; Auger, Donald L; Birchler, James A

    2013-02-12

    The genetic basis of hybrid vigor or heterosis has been debated for more than a century. A popular hypothesis to explain this phenomenon is that there are different slightly deleterious recessive homozygous alleles in the two parents and that these alleles are complemented in the hybrid so that the biomass and fertility exceed both parents. To address the complementation hypothesis in a direct manner, heterosis was examined in diploid inbreds and reciprocal hybrids and compared with matched triploid inbred derivatives and two types of triploid hybrids that differ in the number of genomes from the different parents. Complementation of recessive mutations would occur equally in the two types of triploid hybrids predicting that, if this complementation were the sole basis of the heterotic response, the two types of triploid hybrids would be equivalent for hybrid vigor. However, the reciprocal diploid hybrids were similar for six of nine measured traits, but the two types of triploid hybrids differed significantly for eight of the same traits. Importantly, the triploid hybrids differed in the level of high-parent heterosis relative to the derived triploid inbreds. Also, the differences observed between the reciprocal triploid hybrids correlated strongly with differences observed between the inbreds, either at the diploid or triploid level, in a manner explicable by genome dosage rather than parent of origin effects. The findings of this study suggest that a major component of heterosis is a mechanism that is modulated by dosage-sensitive factors that involves allelic diversity across the genome.

  20. Stability of pharmaceutical salts in solid oral dosage forms.

    PubMed

    Nie, Haichen; Byrn, Stephen R; Zhou, Qi Tony

    2017-03-09

    Using pharmaceutical salts in solid dosage forms can raise stability concerns, especially salt dissociation which can adversely affect the product performance. Therefore, a thorough understanding of the salt instability encountered in solid state formulations is imperative to ensure the product quality. The present article uses the fundamental theory of acid base, ionic equilibrium, relationship of pH and solubility as a starting point to illustrate and interpret the salt formation and salt disproportionation in pharmaceutical systems. The criteria of selecting the optimal salt form and the underlying theory of salt formation and disproportionation are reviewed in detail. Factors influencing salt stability in solid dosage forms are scrutinized and discussed with the case studies. In addition, both commonly used and innovative strategies for preventing salt dissociations in formulation, on storage, and during manufacturing will be suggested herein. This article will provide formulation scientists and manufacturing engineers an insight into the mechanisms of salt disproportionation and salt formation, which can help them avoid and solve the instability issues of pharmaceutical salts in the product design.

  1. Biowaiver monographs for immediate release solid oral dosage forms: metronidazole.

    PubMed

    Rediguieri, Camila F; Porta, Valentina; G Nunes, Diana S; Nunes, Taina M; Junginger, Hans E; Kopp, Sabine; Midha, Kamal K; Shah, Vinod P; Stavchansky, Salomon; Dressman, Jennifer B; Barends, Dirk M

    2011-05-01

    Literature data relevant to the decision to allow a waiver of in vivo bioequivalence (BE) testing for the approval of immediate release (IR) solid oral dosage forms containing metronidazole are reviewed. Metronidazole can be assigned to Biopharmaceutics Classification System Class I. Most BE studies that were identified reported the investigated formulations to be bioequivalent, indicating the risk of bioinequivalence to be low. Formulations showing differences in bioavailability showed dissimilarities in in vitro dissolution profiles. Furthermore, metronidazole has a wide therapeutic index. It is concluded that a biowaiver for solid IR formulations is justified, provided: (a) the test product and its comparator are both rapidly dissolving; (b) meet similarity of the dissolution profiles at pH 1.2, 4.5, and 6.8; (c) the test product contains only excipients present in IR drug products approved in International Conference on Harmonisation (ICH) or associated countries in the same dosage form; and (d) if the test product contains sorbitol, sodium laurilsulfate, or propylene glycol, the test product needs to be qualitatively and quantitatively identical to its comparator with respect to these excipients [corrected]..

  2. Biowaiver monographs for immediate release solid oral dosage forms: efavirenz.

    PubMed

    Cristofoletti, Rodrigo; Nair, Anita; Abrahamsson, Bertil; Groot, D W; Kopp, Sabine; Langguth, Peter; Polli, James E; Shah, Vinod P; Dressman, Jennifer B

    2013-02-01

    Literature data pertaining to the decision to allow a waiver of in vivo bioequivalence testing for the approval of immediate-release (IR) solid oral dosage forms containing efavirenz as the only active pharmaceutical ingredient (API) are reviewed. Because of lack of conclusive data about efavirenz's permeability and its failure to comply with the "high solubility" criteria according to the Biopharmaceutics Classification System (BCS), the API can be classified as BCS Class II/IV. In line with the solubility characteristics, the innovator product does not meet the dissolution criteria for a "rapidly dissolving product." Furthermore, product variations containing commonly used excipients or in the manufacturing process have been reported to impact the rate and extent of efavirenz absorption. Despite its wide therapeutic index, subtherapeutic levels of efavirenz can lead to treatment failure and also facilitate the emergence of efavirenz-resistant mutants. For all these reasons, a biowaiver for IR solid oral dosage forms containing efavirenz as the sole API is not scientifically justified for reformulated or multisource drug products.

  3. Cirque du Monde as a health intervention

    PubMed Central

    Fournier, Cynthia; Drouin, Mélodie-Anne; Marcoux, Jérémie; Garel, Patricia; Bochud, Emmanuel; Théberge, Julie; Aubertin, Patrice; Favreau, Gil; Fleet, Richard

    2014-01-01

    Abstract Objective To present Cirque du Soleil’s social circus program, Cirque du Monde, to explore its potential as a primary health care tool for family physicians. Data sources A review of the literature in PubMed, the Cochrane Library, PsycINFO, LaPresse, Eureka, Google Scholar, and Érudit using the key words circus, social circus, Cirque du Monde, and Cirque du Soleil; a Montreal-based initiative, Espace Transition, modeled on Cirque du Monde; and personal communication with Cirque du Soleil’s Social Circus Training Advisor. Study selection The first 50 articles or websites identified for each key word in each of the databases were examined on the basis of their titles and abstracts in the case of articles, and on the basis of their titles and page content in the case of websites. Articles and websites that explored an aspect of social circuses or that described an intervention that involved circuses were then retained for analysis. Because all literature on social circuses was searched, no criterion for year of publication was used. Synthesis No articles on the social circus as a health intervention were found. One study on the use of the circus as an intervention in schools was identified. It demonstrated an increase in self-esteem in the children who took part. One study on the use of the circus in a First Nations community was found; it contained nonspecific, qualitative findings. The other articles identified were merely descriptions of social circuses. One website was identified on the use of the social circus to help youth who had been treated in a hospital setting for major psychiatric disorders to re-enter the community. The team in the pediatric psychiatry department at Centre Hospitalier Universitaire Sainte-Justine, the children’s hospital in Montreal, Que, was contacted; they were leading this project, called Espace Transition. The unpublished preliminary findings of its pilot project demonstrate substantial improvements in overall patient

  4. Non-Canonical and Sexually Dimorphic X Dosage Compensation States in the Mouse and Human Germline.

    PubMed

    Sangrithi, Mahesh N; Royo, Helene; Mahadevaiah, Shantha K; Ojarikre, Obah; Bhaw, Leena; Sesay, Abdul; Peters, Antoine H F M; Stadler, Michael; Turner, James M A

    2017-02-06

    Somatic X dosage compensation requires two mechanisms: X inactivation balances X gene output between males (XY) and females (XX), while X upregulation, hypothesized by Ohno and documented in vivo, balances X gene with autosomal gene output. Whether X dosage compensation occurs in germ cells is unclear. We show that mouse and human germ cells exhibit non-canonical X dosage states that differ from the soma and between the sexes. Prior to genome-wide reprogramming, X upregulation is present, consistent with Ohno's hypothesis. Subsequently, however, it is erased. In females, erasure follows loss of X inactivation, causing X dosage excess. Conversely, in males, erasure leads to permanent X dosage decompensation. Sex chromosomally abnormal models exhibit a "sex-reversed" X dosage state: XX males, like XX females, develop X dosage excess, while XO females, like XY males, develop X dosage decompensation. Thus, germline X dosage compensation states are determined by X chromosome number, not phenotypic sex. These unexpected differences in X dosage compensation states between germline and soma offer unique perspectives on sex chromosome infertility.

  5. [Adjusting the dosage of netilmicin from two measurements. Program validation].

    PubMed

    Guedes, Y; Abgrall, J F; Lebot, M A; Voirin, T; L'Azou, D; Dheilly, M; Tanguy, R L; Le Garrec, J

    1989-01-01

    The aim of this study is to give to clinicians a well validated usefull tool allowing an increase of safety in the monitoring of netilmicin. During the first administration of the drug, two plasmatic concentrations are measured, and input in a preprogrammed hand-held calculator. A posology and a rythm of administration are returned by the calculator. After six days of this dosage regiment, the peak and the valley concentrations are compared with those previously given by the computer as values at equilibrium. No significant difference can be observed. There is no change in plasmatic creatinine level from the first to the sixth day of treatment. So, a preprogrammed hand-held computer can be convenient and safe to monitor netilmicin.

  6. REFLECTIONS ON QUALITY AND DOSAGE OF PRESCHOOL AND CHILDREN'S DEVELOPMENT.

    PubMed

    Votruba-Drzal, Elizabeth; Miller, Portia

    2016-06-01

    This ambitious monograph tackles several important questions related to children's preschool experiences that have relevance for program and policy initiatives at the state and federal levels. The authors' approach is rigorous: they conduct parallel analyses across eight large and diverse studies of preschool children in center care and use meta-analysis to summarize patterns across studies. The study finds nonlinear associations between preschool quality and gains in language and literacy skills, with larger associations in higher versus lower quality classrooms. Results also show that domain-specific measures of preschool quality were more strongly related to children's development than global quality measures. The "dosage" of preschool was likewise important: more years in Head Start predicted larger vocabulary and literacy gains, whereas more time spent on instruction predicted greater literacy and math skills growth. In this commentary, we situate these findings in the broader literature addressing links between preschool experiences and children's development and discuss key takeaways for research, practice, and policy.

  7. A general lack of compensation for gene dosage in yeast

    PubMed Central

    Springer, Michael; Weissman, Jonathan S; Kirschner, Marc W

    2010-01-01

    Gene copy number variation has been discovered in humans, between related species, and in different cancer tissues, but it is unclear how much of this genomic-level variation leads to changes in the level of protein abundance. To address this, we eliminated one of the two genomic copies of 730 different genes in Saccharomyces cerevisiae and asked how often a 50% reduction in gene dosage leads to a 50% reduction in protein level. For at least 80% of genes tested, and under several environmental conditions, it does: protein levels in the heterozygous strain are close to 50% of wild type. For <5% of the genes tested, the protein levels in the heterozygote are maintained at nearly wild-type levels. These experiments show that protein levels are not, in general, directly monitored and adjusted to a desired level. Combined with fitness data, this implies that proteins are expressed at levels higher than necessary for survival. PMID:20461075

  8. Dosage-Dependent Modifiers of Homoeotic Mutations in Drosophila melanogaster

    PubMed Central

    Kennison, James A.; Russell, Michael A.

    1987-01-01

    The determination of segment identity in Drosophila melanogaster appears to be controlled by a small number of genes. In order to identity new components in the process, we have systematically screened the autosomal complement for loci that show a dosage-dependent interaction with mutations in previously characterized genes thought to be important in the determination of segment identity. The dominant homoeotic phenotype of mutations at four loci involved in thoracic leg determination (Pc, Pcl, Antp and Scr) were quantitated in flies bearing a series of synthetic duplications covering more than 99% of the autosomal complement. Twelve regions were identified that when present in three wild-type copies strongly enhanced or suppressed the phenotype of mutations at one or more of the four homoeotic loci examined. The effects of five of these regions appear to correspond to previously described homoeotic loci; the effects of the remaining seven appear to identify new loci involved in the determination of segment identity. PMID:17246380

  9. Dosage of intrathecal baclofen maintenance therapy in the spastic syndromes.

    PubMed

    Fares, Youssef; Khazim, Rabi M; del Barrio, E R; Burzaco, J A

    2004-01-01

    Twenty-three patients affected with severe spasticity as a result of several clinical pathologies were treated with intrathecal Baclofen and administered at a lumbar level by means of an implantable infusion system. The system allows programming of any drug dosage in a continuous infusion fashion in the subarachnoid space. The appropriate patients were selected using specific criteria and the patients were regularly reviewed regarding the level of the spasticity and functional capacity. The required daily doses were determined using a specific detailed system. The doses needed varied according to the pathologic or clinical diagnosis. The doses administered by the global method at the beginning of the treatment were 91.96 microg/day and 137.81 microg/day in the final phase. These doses were higher in patients with medullary traumatic lesion, diffuse cerebral lesion and spastic idiopathic paraparesis. Relatively mild side effects were produced by the therapeutic doses used.

  10. Biowaiver monographs for immediate release solid oral dosage forms: ibuprofen.

    PubMed

    Potthast, H; Dressman, J B; Junginger, H E; Midha, K K; Oeser, H; Shah, V P; Vogelpoel, H; Barends, D M

    2005-10-01

    Literature data are reviewed on the properties of ibuprofen related to the biopharmaceutics classification system (BCS). Ibuprofen was assessed to be a BCS class II drug. Differences in composition and/or manufacturing procedures were reported to have an effect on the rate, but not the extent of absorption; such differences are likely to be detectable by comparative in vitro dissolution tests. Also in view of its therapeutic use, its wide therapeutic index and uncomplicated pharmacokinetic properties, a biowaiver for immediate release (IR) ibuprofen solid oral drug products is scientifically justified, provided that the test product contains only those excipients reported in this paper in their usual amounts, the dosage form is rapidly dissolving (85% in 30 min or less) in buffer pH 6.8 and the test product also exhibits similar dissolution profiles to the reference product in buffer pH 1.2, 4.5, and 6.8.

  11. Biowaiver monographs for immediate release solid oral dosage forms: acetazolamide.

    PubMed

    Granero, G E; Longhi, M R; Becker, C; Junginger, H E; Kopp, S; Midha, K K; Shah, V P; Stavchansky, S; Dressman, J B; Barends, D M

    2008-09-01

    Literature data relevant to the decision to allow a waiver of in vivo bioequivalence (BE) testing for the approval of immediate release (IR) solid oral dosage forms containing acetazolamide are reviewed. Acetazolamide's solubility and permeability characteristics according to the Biopharmaceutics Classification System (BCS), as well as its therapeutic use and therapeutic index, its pharmacokinetic properties, data related to the possibility of excipient interactions and reported BE/bioavailability (BA) problems are taken into consideration. The available data on solubility, on oral absorption and permeability are not sufficiently conclusive to classify acetazolamide with certainty. Taking a conservative approach, no biowaiver is considered justified for the registration of new multisource drug products. However, SUPAC level 1 and level 2 postapproval changes and most EU Type I variations can be approved waiving in vivo BE studies.

  12. Biowaiver monographs for immediate release solid oral dosage forms: furosemide.

    PubMed

    Granero, G E; Longhi, M R; Mora, M J; Junginger, H E; Midha, K K; Shah, V P; Stavchansky, S; Dressman, J B; Barends, D M

    2010-06-01

    Literature and new experimental data relevant to the decision to allow a waiver of in vivo bioequivalence (BE) testing for the approval of immediate release (IR) solid oral dosage forms containing furosemide are reviewed. The available data on solubility, oral absorption, and permeability are sufficiently conclusive to classify furosemide into Class IV of the Biopharmaceutics Classification System (BCS). Furosemide's therapeutic use and therapeutic index, its pharmacokinetic properties, data related to the possibility of excipient interactions and reported BE/bioavailability (BA) problems are also taken into consideration. In view of the data available, it is concluded that the biowaiver procedure cannot be justified for either the registration of new multisource drug products or major postapproval changes (variations) to existing drug products.

  13. Biowaiver monographs for immediate release solid oral dosage forms: cimetidine.

    PubMed

    Jantratid, E; Prakongpan, S; Dressman, J B; Amidon, G L; Junginger, H E; Midha, K K; Barends, D M

    2006-05-01

    Literature data relevant to the decision to allow a waiver of in vivo bioequivalence (BE) testing for the approval of immediate release (IR) solid oral dosage forms containing cimetidine are reviewed. According to the current Biopharmaceutics Classification System (BCS), cimetidine would be assigned to Class III. Cimetidine's therapeutic use and therapeutic index, its pharmacokinetic properties, data related to the possibility of excipient interactions, and reported BE/bioavailability (BA) problems were also taken into consideration. On the basis of the overall evidence, a biowaiver can be recommended for cimetidine IR products, provided that the test product contains only those excipients reported in this paper in their usual amounts, and that the test and the comparator drug products both are "rapidly dissolving" as per BCS.

  14. Long-acting injectable hormonal dosage forms for contraception.

    PubMed

    Wu, Linfeng; Janagam, Dileep R; Mandrell, Timothy D; Johnson, James R; Lowe, Tao L

    2015-07-01

    Although great efforts have been made to develop long-acting injectable hormonal contraceptives for more than four decades, few long-acting injectable contraceptives have reached the pharmaceutical market or even entered clinical trials. On the other hand, in clinical practice there is an urgent need for injectable long-acting reversible contraceptives which can provide contraceptive protection for more than 3 months after one single injection. Availability of such products will offer great flexibility to women and resolve certain continuation issues currently occurring in clinics. Herein, we reviewed the strategies exploited in the past to develop injectable hormonal contraceptive dosages including drug microcrystal suspensions, drug-loaded microsphere suspensions and in situ forming depot systems for long-term contraception and discussed the potential solutions for remaining issues met in the previous development.

  15. Normal spastin gene dosage is specifically required for axon regeneration

    PubMed Central

    Stone, Michelle C.; Rao, Kavitha; Gheres, Kyle W.; Kim, Seahee; Tao, Juan; Rochelle, Caroline La; Folker, Christin T.; Sherwood, Nina T.; Rolls, Melissa M.

    2012-01-01

    Summary Axon regeneration allows neurons to repair circuits after trauma, but most of the molecular players remain to be identified. As microtubule rearrangements have been observed in injured neurons, we tested whether microtubule severing proteins might play a role in axon regeneration. We found that axon regeneration is extremely sensitive to levels of the microtubule severing protein spastin. While microtubule behavior in uninjured neurons was not perturbed in animals heterozygous for a spastin null allele, axon regeneration was severely disrupted in this background. Two types of axon regeneration, regeneration of an axon from a dendrite after proximal axotomy and regeneration of an axon from the stump after distal axotomy, were defective in Drosophila with one mutant copy of the spastin gene. Other types of axon and dendrite outgrowth, including regrowth of dendrites after pruning, were normal in heterozygotes. We conclude that regenerative axon growth is uniquely sensitive to spastin gene dosage. PMID:23122959

  16. Cri du Chat: report of a case.

    PubMed

    Sparks, S; Hutchinson, B

    1980-01-01

    Since Lejeune et al. (1963) first described the syndrome of Cri du Chat (Cry of the Cat), cases have been described in the literature in terms of genetic abnormalities. All cases were severely retarded and the mental impairment has been believed to be progressive, although no longitudinal studies have been reported. Descriptions of speech and language behavior have been scarce. This paper presents a case of a 7-yr, 6 mo-old girl with Cri du Chat who has received speech and language therapy for five years. Her speech, language, and mental development are noted and are not consistent with cases reported previously.

  17. Struvite precipitation from urine with electrochemical magnesium dosage.

    PubMed

    Hug, Alexandra; Udert, Kai M

    2013-01-01

    When magnesium is added to source-separated urine, struvite (MgNH(4)PO(4)·6H(2)O) precipitates and phosphorus can be recovered. Up to now, magnesium salts have been used as the main source of magnesium. Struvite precipitation with these salts works well but is challenging in decentralized reactors, where high automation of the dosage and small reactor sizes are required. In this study, we investigated a novel approach for magnesium dosage: magnesium was electrochemically dissolved from a sacrificial magnesium electrode. We demonstrated that this process is technically simple and economically feasible and thus interesting for decentralized reactors. Linear voltammetry and batch experiments at different anode potentials revealed that the anode potential must be higher than -0.9 V vs. NHE (normal hydrogen electrode) to overcome the strong passivation of the anode. An anode potential of -0.6 V vs. NHE seemed to be suitable for active magnesium dissolution. For 13 subsequent cycles at this potential, we achieved an average phosphate removal rate of 3.7 mg P cm(-2) h(-1), a current density of 5.5 mA cm(-2) and a current efficiency of 118%. Some magnesium carbonate (nesquehonite) accumulated on the anode surface; as a consequence, the current density decreased slightly, but the current efficiency was not affected. The energy consumption for these experiments was 1.7 W h g P(-1). A cost comparison showed that sacrificial magnesium electrodes are competitive with easily soluble magnesium salts such as MgCl(2) and MgSO(4), but are more expensive than dosing with MgO. Energy costs for the electrochemical process were insignificant. Dosing magnesium electrochemically could thus be a worthwhile alternative to dosing magnesium salts. Due to the simple reactor and handling of magnesium, this may well be a particularly interesting approach for decentralized urine treatment.

  18. Biowaiver monographs for immediate release solid oral dosage forms: piroxicam.

    PubMed

    Shohin, Igor E; Kulinich, Julia I; Ramenskaya, Galina V; Abrahamsson, Bertil; Kopp, Sabine; Langguth, Peter; Polli, James E; Shah, Vinod P; Groot, D W; Barends, Dirk M; Dressman, Jennifer B

    2014-02-01

    Literature and experimental data relevant to the decision to allow a waiver of in vivo bioequivalence (BE) testing for the approval of immediate release (IR) solid oral dosage forms containing piroxicam in the free acid form are reviewed. Piroxicam solubility and permeability, its therapeutic use and therapeutic index, pharmacokinetic properties, data related to the possibility of excipient interactions and reported BE/bioavailability (BA), and corresponding dissolution data are taken into consideration. The available data suggest that according to the current biopharmaceutics classification system (BCS) and all current guidances, piroxicam would be assigned to BCS Class II. The extent of piroxicam absorption seems not to depend on manufacturing conditions or excipients, so the risk of bioinequivalence in terms of area under the curve (AUC) is very low, but the rate of absorption (i.e., BE in terms of Cmax ) can be affected by the formulation. Current in vitro dissolution methods may not always reflect differences in terms of Cmax for BCS Class II weak acids; however, minor differences in absorption rate of piroxicam would not subject the patient to unacceptable risks: as piroxicam products may be taken before or after meals, the rate of absorption cannot be considered crucial to drug action. Therefore, a biowaiver for IR piroxicam solid oral dosage form is considered feasible, provided that (a) the test product contains only excipients, which are also present in IR solid oral drug products containing piroxicam, which have been approved in ICH or associated countries, for instance, those presented in Table 3 of this paper; (b) both the test and comparator drug products dissolve 85% in 30 min or less at pH 1.2, 4.5, and 6.8; and (c) the test product and comparator show dissolution profile similarity in pH 1.2, 4.5, and 6.8. When not all of these conditions can be fulfilled, BE of the products should be established in vivo.

  19. Over-the-counter pharmaceuticals: exploratory research of consumer preference toward solid oral dosage forms.

    PubMed

    Reisenwitz, T H; Wimbish, G J

    1996-01-01

    The capsule dosage form in nonprescription pharmaceuticals persists as being one of the most vulnerable to product tampering. This study examines consumer preference toward three solid oral dosage forms (capsules, caplets, and tablets) in nonprescription products. Thirteen independent variables representing dosage form attributes are measured on semantic differential scales. The data are analyzed using analysis of variance (ANOVA) and factor analysis. Implications for the pharmaceutical marketer are noted. Future directions for research are also outlined.

  20. Biliary excretion of diazepam in rats: influence of the route of administration and dosage.

    PubMed

    Phillips, R; Plaa, G L

    1981-01-01

    The biliary excretion of diazepam metabolites was found in rats. Equivalent dosages of diazepam were administered orally and intraperitoneally. The biliary excretion was dose-dependent and was greater following intraperitoneal administration. After intravenous administration, a greater percentage of the diazepam dosage administered was excreted into the bile. Repetitive intravenous administrations yielded results which approached those observed after intraperitoneally administered dosages given as a bolus.

  1. Génotypes du virus de l'hépatite B et marqueurs évolutifs des patients porteurs chroniques de l'AgHBs à Bujumbura

    PubMed Central

    Ntagirabiri, Rénovat; Munezero, Belyse; Nahimana, Caritas; Ndabaneze, Evariste

    2016-01-01

    Introduction L'infection par le virus de l'hépatite B (VHB) est une affection grave suite à ses complications notamment la cirrhose et le carcinome hépatocellulaire (CHC). Les génotypes du VHB influent beaucoup sur son évolution et sur l'efficacité du traitement. Le but était d’évaluer les génotypes du VHB et les profils évolutifs des patients porteurs chroniques de l'AgHBs. Méthodes Étude transversale, menée au Centre hospitalo-universitaire de Kamenge et au Centre des maladies du tube digestif et du foie « CEMADIF » entre Juin 2013 et Mai 2014. Le génotypage, les dosages quantitatifs de l'AgHBe et de l'ADN virale B ont été réalisés au Laboratoire Cerba, Cergy Pontoise, France. L’évaluation de la fibrose était faite par le Fibrotest ou le FibroScan. Résultats Au total, 143 patients, 52,4% de sexe masculin, âge moyen 38,1 ans ont été inclus. Selon les marqueurs évolutifs, 112 patients (78,3%) avaient un AgHBe négatif. Quant à la charge virale, 106 patients (74,2%) avaient une virémie inférieure à 2000UI/ml et une fibrose minime inférieure à 7kpa selon le FibroScan. Parmi eux, 13 malades avaient un ADN du VHB indétectable (<20UI/ml). Les autres 37 patients (26,8%) avaient une charge virale supérieure à 2000UI/ml et parmi eux, 31 avaient un AgHBe positif (>0,8UI/ml). Il a été possible de déterminer le génotype chez 51 patients qui avaient une virémie assez élevée pour permettre techniquement ce dosage. Ces patients avaient tous un génotype A. Conclusion Le génotype A du VHB est le plus fréquent à Bujumbura. Il est associé à un portage inactif élevé. PMID:27222687

  2. 10 CFR 35.63 - Determination of dosages of unsealed byproduct material for medical use.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ...) For a unit dosage, this determination must be made by— (1) Direct measurement of radioactivity; or (2... measurement of radioactivity; (2) Combination of measurement of radioactivity and mathematical...

  3. 10 CFR 35.63 - Determination of dosages of unsealed byproduct material for medical use.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ...) For a unit dosage, this determination must be made by— (1) Direct measurement of radioactivity; or (2... measurement of radioactivity; (2) Combination of measurement of radioactivity and mathematical...

  4. 10 CFR 35.63 - Determination of dosages of unsealed byproduct material for medical use.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ...) For a unit dosage, this determination must be made by— (1) Direct measurement of radioactivity; or (2... measurement of radioactivity; (2) Combination of measurement of radioactivity and mathematical...

  5. 10 CFR 35.63 - Determination of dosages of unsealed byproduct material for medical use.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ...) For a unit dosage, this determination must be made by— (1) Direct measurement of radioactivity; or (2... measurement of radioactivity; (2) Combination of measurement of radioactivity and mathematical...

  6. 10 CFR 35.63 - Determination of dosages of unsealed byproduct material for medical use.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ...) For a unit dosage, this determination must be made by— (1) Direct measurement of radioactivity; or (2... measurement of radioactivity; (2) Combination of measurement of radioactivity and mathematical...

  7. Compensation of Dosage-Sensitive Genes on the Chicken Z Chromosome

    PubMed Central

    Zimmer, Fabian; Harrison, Peter W.; Dessimoz, Christophe; Mank, Judith E.

    2016-01-01

    In many diploid species, sex determination is linked to a pair of sex chromosomes that evolved from a pair of autosomes. In these organisms, the degeneration of the sex-limited Y or W chromosome causes a reduction in gene dose in the heterogametic sex for X- or Z-linked genes. Variations in gene dose are detrimental for large chromosomal regions when they span dosage-sensitive genes, and many organisms were thought to evolve complete mechanisms of dosage compensation to mitigate this. However, the recent realization that a wide variety of organisms lack complete mechanisms of sex chromosome dosage compensation has presented a perplexing question: How do organisms with incomplete dosage compensation avoid deleterious effects of gene dose differences between the sexes? Here we use expression data from the chicken (Gallus gallus) to show that ohnologs, duplicated genes known to be dosage-sensitive, are preferentially dosage-compensated on the chicken Z chromosome. Our results indicate that even in the absence of a complete and chromosome wide dosage compensation mechanism, dosage-sensitive genes are effectively dosage compensated on the Z chromosome. PMID:27044516

  8. Variete Technique du Lambeau Sural dans les Brulures Profondes du Pied

    PubMed Central

    Ezzoubi, M.; Ettalbi, S.; Elmounjid, S.; Fassi, J.; Benchamckha, F.J.; Sakhi, M.; Boukind, E.

    2005-01-01

    Summary Les couvertures des pertes de substance de la jambe, du talon et du pied font souvent appel au lambeau sural, qui reste, de part ses dimensions, une indication limitée. Les Auteurs présentent, à travers deux cas cliniques, une variété technique pour la levée du lambeau sural, permettant d'obtenir des palettes cutanées de grande surface avec une bonne sécurité vasculaire. C'est un lambeau fasciocutané remontant jusqu'à un centimètre du creux poplité et incluant, lors de la levée, l'aponévrose, le nerf sural, la petite veine saphène et le nerf sural latéral. PMID:21990988

  9. Sign Communication in Cri du Chat Syndrome

    ERIC Educational Resources Information Center

    Erlenkamp, Sonja; Kristoffersen, Kristian Emil

    2010-01-01

    This paper presents findings from a study on the use of sign supported Norwegian (SSN) in two individuals with Cri du chat syndrome (CCS). The study gives a first account of some selected aspects of production and intelligibility of SSN in CCS. Possible deviance in manual parameters, in particular inter- and/or intra-subject variation in the use…

  10. Prejudice: From Allport to DuBois.

    ERIC Educational Resources Information Center

    Gaines, Stanley O., Jr.; Reed, Edward S.

    1995-01-01

    Examines the differences between Gordon Allport's and W. E. B. DuBois's theories on the origins of prejudice and the impact of discrimination on the personality and social development of blacks. The article argues that prejudice is a historically developed process, not a universal feature of human psychology. Implications for U.S. race relations…

  11. Growth study of cri du chat syndrome.

    PubMed

    Collins, M S; Eaton-Evans, J

    2001-10-01

    We compared the growth of children with cri du chat (5p-) syndrome with the 1990 UK growth curves. Most subjects had impaired growth, particularly of head circumference. The more emaciated the child the more pronounced the microcephaly, showing the need for growth and nutrition monitoring.

  12. Rick and Becky DuFour

    ERIC Educational Resources Information Center

    McLester, Susan

    2012-01-01

    In 1969, a concern with the deep inequity of students' experiences and opportunities in traditional school systems first drove social studies teacher Rick DuFour to begin advocating for the kind of reforms that would jell into his transformative model, Professional Learning Communities (PLC) at Work, some 16 years later. The core belief of the PLC…

  13. DuSable High School Program Flourishes.

    ERIC Educational Resources Information Center

    Graff, Pat

    1995-01-01

    Describes the fall and rise of the Panther Press, the scholastic newspaper of the DuSable High School in Chicago. States that despite being located in the midst of public housing projects, the school's newspaper is thriving where others in similar circumstances have failed. Describes how the school's principal and an advisor revitalized and…

  14. [Natural biopolymers as excipients in medicinal product dosage form. Part I. Soft gelatin capsules as a modern and elegant pharmaceutical dosage form].

    PubMed

    Dobrzyński, Łukasz Jerzy; Zgoda, Marian Mikołaj

    2010-01-01

    Soft gelatin capsules (Softgels) are modern and effective pharmaceutical dosage form for the administration of many medicinal products and food supplements formulations. In this short article major advantages and disadvantages of soft gelatin capsules are reviewed. Each step of manufacturing focused on fundamental techniques and requirements for developing and manufacturing technology for soft gelatin capsules is provided. Main role, characteristics, raw material, manufacturing techniques and applications in dosage form of gelatin is discussed. The review of recent advances in softgels are also included.

  15. Dosage optimization in positron emission tomography: state-of-the-art methods and future prospects.

    PubMed

    Karakatsanis, Nicolas A; Fokou, Eleni; Tsoumpas, Charalampos

    2015-01-01

    Positron emission tomography (PET) is widely used nowadays for tumor staging and therapy response in the clinic. However, average PET radiation exposure has increased due to higher PET utilization. This study aims to review state-of-the-art PET tracer dosage optimization methods after accounting for the effects of human body attenuation and scan protocol parameters on the counting rate. In particular, the relationship between the noise equivalent count rate (NECR) and the dosage (NECR-dosage curve) for a range of clinical PET systems and body attenuation sizes will be systematically studied to prospectively estimate the minimum dosage required for sufficiently high NECR. The optimization criterion can be determined either as a function of the peak of the NECR-dosage curve or as a fixed NECR score when NECR uniformity across a patient population is important. In addition, the systematic NECR assessments within a controllable environment of realistic simulations and phantom experiments can lead to a NECR-dosage response model, capable of predicting the optimal dosage for every individual PET scan. Unlike conventional guidelines suggesting considerably large dosage levels for obese patients, NECR-based optimization recommends: i) moderate dosage to achieve 90% of peak NECR for obese patients, ii) considerable dosage reduction for slimmer patients such that uniform NECR is attained across the patient population, and iii) prolongation of scans for PET/MR protocols, where longer PET acquisitions are affordable due to lengthy MR sequences, with motion compensation becoming important then. Finally, the need for continuous adaptation of dosage optimization to emerging technologies will be discussed.

  16. Relative Bioavailability of Scopolamine Dosage Forms and Interaction with Dextroamphetamine

    NASA Technical Reports Server (NTRS)

    Boyd, Jason L.; Du, Brian; Vaksman, Zalman; Locke, James P.; Putcha, Lakshmi

    2007-01-01

    The NASA Reduced Gravity Office (RGO) uses scopolamine (SCOP) and in combination with dextoamphetamine (DEX) to manage motion sickness symptoms during parabolic flights. The medications are dispensed as custom dosage forms as gelatin capsules. Anecdotal evidence of efficacy suggests that these formulations are unreliable and less efficacious for the treatment of motion sickness. We estimated bioavailability of four different oral formulations used by NASA for the treatment of motion sickness. Twelve healthy, non-smoking subjects between 21and 48 years of age received four treatments on separate days in a randomized fashion; the treatments were 0.8 mg SCOP alone as tablet, 0.8 mg SCOP alone in gel cap, 0.8 mg SCOP and 10 mg DEX as tablets, and 0.8 mg SCOP and 10 mg DEX in gel cap. After each treatment, blood, saliva, and urine samples were collected at scheduled time intervals for 24 h after dosing. Bioavailability and pharmacokinetic parameters were calculated and compared using ANOVA. After administration of SCOP tablets alone, maximum concentration (C(sub max)) and time for maximum concentration (t(sub max)) were 0.26 plus or minus 0.04 ng/mL and 0.71 plus or minus 0.02 h, respectively; volume of distribution, and clearance were 47.6 plus or minus 4.72 L/kg and 23.0 plus or minus 4.58 L/h/kg, respectively. SCOP t(sub max) after administration as gelcaps was significantly longer than that with tablets (1.04 h, p less than 0.05), but no significant differences in other pharmacokinetic parameters of SCOP were observed between the two dosage forms. When coadministered with DEX, the area underneath the concentration versus time curve (AUC) of SCOP was significantly reduced to 0.61 plus or minus 0.09 and 0.64 plus or minus 0.11 ng (raised dot) h/mL after administration as a tablet or gelcap formulation, respectively; SCOP C(sub max) was lower after coadministration with DEX, this difference, however, was not statistically significant. Delayed absorption with gelcaps

  17. Evolution of dosage compensation in Diptera: the gene maleless implements dosage compensation in Drosophila (Brachycera suborder) but its homolog in Sciara (Nematocera suborder) appears to play no role in dosage compensation.

    PubMed

    Ruiz, M F; Esteban, M R; Doñoro, C; Goday, C; Sánchez, L

    2000-12-01

    In Drosophila melanogaster and in Sciara ocellaris dosage compensation occurs by hypertranscription of the single male X chromosome. This article reports the cloning and characterization in S. ocellaris of the gene homologous to maleless (mle) of D. melanogaster, which implements dosage compensation. The Sciara mle gene produces a single transcript, encoding a helicase, which is present in both male and female larvae and adults and in testes and ovaries. Both Sciara and Drosophila MLE proteins are highly conserved. The affinity-purified antibody to D. melanogaster MLE recognizes the S. ocellaris MLE protein. In contrast to Drosophila polytene chromosomes, where MLE is preferentially associated with the male X chromosome, in Sciara MLE is found associated with all chromosomes. Anti-MLE staining of Drosophila postblastoderm male embryos revealed a single nuclear dot, whereas Sciara male and female embryos present multiple intranuclear staining spots. This expression pattern in Sciara is also observed before blastoderm stage, when dosage compensation is not yet set up. The affinity-purified antibodies against D. melanogaster MSL1, MSL3, and MOF proteins involved in dosage compensation also revealed no differences in the staining pattern between the X chromosome and the autosomes in both Sciara males and females. These results lead us to propose that different proteins in Drosophila and Sciara would implement dosage compensation.

  18. Evolution of dosage compensation in Diptera: the gene maleless implements dosage compensation in Drosophila (Brachycera suborder) but its homolog in Sciara (Nematocera suborder) appears to play no role in dosage compensation.

    PubMed Central

    Ruiz, M F; Esteban, M R; Doñoro, C; Goday, C; Sánchez, L

    2000-01-01

    In Drosophila melanogaster and in Sciara ocellaris dosage compensation occurs by hypertranscription of the single male X chromosome. This article reports the cloning and characterization in S. ocellaris of the gene homologous to maleless (mle) of D. melanogaster, which implements dosage compensation. The Sciara mle gene produces a single transcript, encoding a helicase, which is present in both male and female larvae and adults and in testes and ovaries. Both Sciara and Drosophila MLE proteins are highly conserved. The affinity-purified antibody to D. melanogaster MLE recognizes the S. ocellaris MLE protein. In contrast to Drosophila polytene chromosomes, where MLE is preferentially associated with the male X chromosome, in Sciara MLE is found associated with all chromosomes. Anti-MLE staining of Drosophila postblastoderm male embryos revealed a single nuclear dot, whereas Sciara male and female embryos present multiple intranuclear staining spots. This expression pattern in Sciara is also observed before blastoderm stage, when dosage compensation is not yet set up. The affinity-purified antibodies against D. melanogaster MSL1, MSL3, and MOF proteins involved in dosage compensation also revealed no differences in the staining pattern between the X chromosome and the autosomes in both Sciara males and females. These results lead us to propose that different proteins in Drosophila and Sciara would implement dosage compensation. PMID:11102379

  19. 21 CFR 522.1696 - Penicillin G procaine injectable dosage forms.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Penicillin G procaine injectable dosage forms. 522.1696 Section 522.1696 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... ANIMAL DRUGS § 522.1696 Penicillin G procaine injectable dosage forms....

  20. A System for Dosage-Based Functional Genomics in Poplar[OPEN

    PubMed Central

    2015-01-01

    Altering gene dosage through variation in gene copy number is a powerful approach to addressing questions regarding gene regulation, quantitative trait loci, and heterosis, but one that is not easily applied to sexually transmitted species. Elite poplar (Populus spp) varieties are created through interspecific hybridization, followed by clonal propagation. Altered gene dosage relationships are believed to contribute to hybrid performance. Clonal propagation allows for replication and maintenance of meiotically unstable ploidy or structural variants and provides an alternative approach to investigating gene dosage effects not possible in sexually propagated species. Here, we built a genome-wide structural variation system for dosage-based functional genomics and breeding of poplar. We pollinated Populus deltoides with gamma-irradiated Populus nigra pollen to produce >500 F1 seedlings containing dosage lesions in the form of deletions and insertions of chromosomal segments (indel mutations). Using high-precision dosage analysis, we detected indel mutations in ∼55% of the progeny. These indels varied in length, position, and number per individual, cumulatively tiling >99% of the genome, with an average of 10 indels per gene. Combined with future phenotype and transcriptome data, this population will provide an excellent resource for creating and characterizing dosage-based variation in poplar, including the contribution of dosage to quantitative traits and heterosis. PMID:26320226

  1. 21 CFR 524.1200 - Kanamycin ophthalmic and topical dosage forms.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Kanamycin ophthalmic and topical dosage forms. 524.1200 Section 524.1200 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... ANIMAL DRUGS § 524.1200 Kanamycin ophthalmic and topical dosage forms....

  2. 21 CFR 524.1200 - Kanamycin ophthalmic and topical dosage forms.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Kanamycin ophthalmic and topical dosage forms. 524.1200 Section 524.1200 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... ANIMAL DRUGS § 524.1200 Kanamycin ophthalmic and topical dosage forms....

  3. 21 CFR 524.1200 - Kanamycin ophthalmic and topical dosage forms.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Kanamycin ophthalmic and topical dosage forms. 524.1200 Section 524.1200 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... ANIMAL DRUGS § 524.1200 Kanamycin ophthalmic and topical dosage forms....

  4. 21 CFR 524.1200 - Kanamycin ophthalmic and topical dosage forms.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Kanamycin ophthalmic and topical dosage forms. 524.1200 Section 524.1200 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... ANIMAL DRUGS § 524.1200 Kanamycin ophthalmic and topical dosage forms....

  5. 21 CFR 524.1200 - Kanamycin ophthalmic and topical dosage forms.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Kanamycin ophthalmic and topical dosage forms. 524.1200 Section 524.1200 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... ANIMAL DRUGS § 524.1200 Kanamycin ophthalmic and topical dosage forms....

  6. 10 CFR 35.2063 - Records of dosages of unsealed byproduct material for medical use.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 10 Energy 1 2014-01-01 2014-01-01 false Records of dosages of unsealed byproduct material for medical use. 35.2063 Section 35.2063 Energy NUCLEAR REGULATORY COMMISSION MEDICAL USE OF BYPRODUCT MATERIAL Records § 35.2063 Records of dosages of unsealed byproduct material for medical use. (a)...

  7. 10 CFR 35.2063 - Records of dosages of unsealed byproduct material for medical use.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 1 2010-01-01 2010-01-01 false Records of dosages of unsealed byproduct material for medical use. 35.2063 Section 35.2063 Energy NUCLEAR REGULATORY COMMISSION MEDICAL USE OF BYPRODUCT MATERIAL Records § 35.2063 Records of dosages of unsealed byproduct material for medical use. (a)...

  8. 21 CFR 520.1802 - Piperazine-carbon disulfide complex oral dosage forms.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Piperazine-carbon disulfide complex oral dosage forms. 520.1802 Section 520.1802 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND... § 520.1802 Piperazine-carbon disulfide complex oral dosage forms....

  9. 21 CFR 520.1802 - Piperazine-carbon disulfide complex oral dosage forms.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Piperazine-carbon disulfide complex oral dosage forms. 520.1802 Section 520.1802 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND... § 520.1802 Piperazine-carbon disulfide complex oral dosage forms....

  10. 21 CFR 520.1802 - Piperazine-carbon disulfide complex oral dosage forms.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Piperazine-carbon disulfide complex oral dosage forms. 520.1802 Section 520.1802 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND... § 520.1802 Piperazine-carbon disulfide complex oral dosage forms....

  11. 21 CFR 520.1802 - Piperazine-carbon disulfide complex oral dosage forms.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Piperazine-carbon disulfide complex oral dosage forms. 520.1802 Section 520.1802 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND... § 520.1802 Piperazine-carbon disulfide complex oral dosage forms....

  12. 21 CFR 520.1802 - Piperazine-carbon disulfide complex oral dosage forms.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Piperazine-carbon disulfide complex oral dosage forms. 520.1802 Section 520.1802 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND... § 520.1802 Piperazine-carbon disulfide complex oral dosage forms....

  13. 21 CFR 522.1662 - Oxytetracycline hydrochloride implantation or injectable dosage forms.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Oxytetracycline hydrochloride implantation or injectable dosage forms. 522.1662 Section 522.1662 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF... INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.1662 Oxytetracycline hydrochloride implantation or...

  14. 21 CFR 522.90 - Ampicillin implantation and injectible dosage forms.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Ampicillin implantation and injectible dosage forms. 522.90 Section 522.90 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM...

  15. 76 FR 3488 - Implantation or Injectable Dosage Form New Animal Drugs; Oxytetracycline and Flunixin

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-01-20

    ... HUMAN SERVICES Food and Drug Administration 21 CFR Part 522 Implantation or Injectable Dosage Form New... veterinary prescription use of a combination drug injectable solution containing oxytetracycline and flunixin...--IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS 0 1. The authority citation for 21 CFR part...

  16. 21 CFR 522.90 - Ampicillin implantation and injectible dosage forms.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Ampicillin implantation and injectible dosage forms. 522.90 Section 522.90 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM...

  17. 77 FR 4227 - Implantation or Injectable Dosage Form New Animal Drugs; Gonadotropin Releasing Factor Analog...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-27

    ... HUMAN SERVICES Food and Drug Administration 21 CFR Part 522 Implantation or Injectable Dosage Form New... gonadotropin releasing factor analog-diphtheria toxoid conjugate injectable solution. DATES: This rule is...: PART 522--IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS 0 1. The authority citation for...

  18. 21 CFR 522.1662 - Oxytetracycline hydrochloride implantation or injectable dosage forms.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Oxytetracycline hydrochloride implantation or injectable dosage forms. 522.1662 Section 522.1662 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF... INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.1662 Oxytetracycline hydrochloride implantation or...

  19. 75 FR 26647 - Implantation or Injectable Dosage Form New Animal Drugs; Ivermectin

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-05-12

    ... CFR Part 522 [Docket No. FDA-2010-N-0002] Implantation or Injectable Dosage Form New Animal Drugs... ivermectin injectable solution in cattle and swine for treatment and control of various internal and external...--IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS 0 1. The authority citation for 21 CFR part...

  20. 21 CFR 522.2444 - Sodium thiopental implantation or injectable dosage forms.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Sodium thiopental implantation or injectable... AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.2444 Sodium thiopental implantation or injectable dosage forms....

  1. 21 CFR 522.90 - Ampicillin implantation and injectible dosage forms.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Ampicillin implantation and injectible dosage forms. 522.90 Section 522.90 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM...

  2. 76 FR 57905 - Implantation or Injectable Dosage Form New Animal Drugs; Ivermectin

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-19

    ... HUMAN SERVICES Food and Drug Administration 21 CFR Part 522 Implantation or Injectable Dosage Form New... of an ivermectin injectable solution for treatment and control of various internal and external... as follows: PART 522--IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS 0 1. The...

  3. 21 CFR 522.2444 - Sodium thiopental implantation or injectable dosage forms.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Sodium thiopental implantation or injectable... AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.2444 Sodium thiopental implantation or injectable dosage forms....

  4. 21 CFR 522.2444 - Sodium thiopental implantation or injectable dosage forms.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Sodium thiopental implantation or injectable... AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.2444 Sodium thiopental implantation or injectable dosage forms....

  5. 21 CFR 522.90 - Ampicillin implantation and injectible dosage forms.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Ampicillin implantation and injectible dosage forms. 522.90 Section 522.90 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM...

  6. 21 CFR 522.1662 - Oxytetracycline hydrochloride implantation or injectable dosage forms.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Oxytetracycline hydrochloride implantation or injectable dosage forms. 522.1662 Section 522.1662 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF... INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.1662 Oxytetracycline hydrochloride implantation or...

  7. 21 CFR 522.2444 - Sodium thiopental implantation or injectable dosage forms.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Sodium thiopental implantation or injectable... AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.2444 Sodium thiopental implantation or injectable dosage forms....

  8. 21 CFR 522.1662 - Oxytetracycline hydrochloride implantation or injectable dosage forms.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Oxytetracycline hydrochloride implantation or injectable dosage forms. 522.1662 Section 522.1662 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF... INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.1662 Oxytetracycline hydrochloride implantation or...

  9. 21 CFR 522.1662 - Oxytetracycline hydrochloride implantation or injectable dosage forms.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Oxytetracycline hydrochloride implantation or injectable dosage forms. 522.1662 Section 522.1662 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF... INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.1662 Oxytetracycline hydrochloride implantation or...

  10. Spectrofluorimetric determination of aliskiren in dosage forms and urine.

    PubMed

    Aydoğmuş, Zeynep

    2012-01-01

    A new, simple and sensitive spectrofluorimetric method has been developed for the determination of aliskiren (ALS) in dosage forms and human urine. The method is based on the reaction between ALS and fluorescamine in borate buffer solution, pH 9, to give a highly fluorescent derivative which is measured at 482 nm after excitation at 382 nm. The factors affecting the reaction were carefully studied. The fluorescence intensity concentration plots were rectilinear over the range 140-1400 ng/mL with a limit of detection 13.47 ng/mL and limit of quantitation 40.81 ng/mL. The developed method was successfully applied to the analysis of the drug in tablets and human urine; the average recoveries (n = 6) were 99.88 ± 0.38% and 99.57 ± 0.44%, respectively. The analytical performance of the method was fully validated and the results were satisfactory. The stability of the drug was studied by subjecting it to acidic, basic, oxidative and thermal degradation.

  11. Solid lipid extrusion of sustained release dosage forms.

    PubMed

    Reitz, Claudia; Kleinebudde, Peter

    2007-09-01

    The applicability of the solid lipid extrusion process as preparations method for sustained release dosage forms was investigated in this study. Two lipids with similar melting ranges but of different composition, glyceryl palmitostearate (Precirol ATO 5) and glyceryl trimyristate (Dynasan 114), and mixtures of each lipid with 50% or 75% theophylline were extruded at temperatures below their melting ranges. Extrudates were analyzed using differential scanning calorimetry, scanning electron microscopy, porosity measurements and in vitro drug dissolution studies. The possibility of processing lipids by softening instead of complete melting and without subsequent formation of low-melting, metastable polymorphs could be demonstrated. Extrudates based on formulations of glyceryl palmitostearate/theophylline (50:50) and glyceryl trimyristate/theophylline (50:50) showed sustained release properties. An influence of extrusion conditions on the matrix structure was shown for extrudates based on a mixture of glyceryl trimyristate and theophylline (50:50). Glyceryl trimyristate tended to solidify in porous structures after melting. Exceeding a material temperature of 50.5 degrees C led to porous extrudate matrices with a faster drug release. The production of novel, non porous sustained release matrices was possible at a material temperature of 49.5 degrees C. Extrudates based on glyceryl trimyristate/theophylline (50:50) only slight changes in melting enthalpy and stable drug release profiles.

  12. Drug polymorphism and dosage form design: a practical perspective.

    PubMed

    Singhal, Dharmendra; Curatolo, William

    2004-02-23

    Formulators are charged with the responsibility to formulate a product which is physically and chemically stable, manufacturable, and bioavailable. Most drugs exhibit structural polymorphism, and it is preferable to develop the most thermodynamically stable polymorph of the drug to assure reproducible bioavailability of the product over its shelf life under a variety of real-world storage conditions. There are occasional situations in which the development of a metastable crystalline or amorphous form is justified because a medical benefit is achieved. Such situations include those in which a faster dissolution rate or higher concentration are desired, in order to achieve rapid absorption and efficacy, or to achieve acceptable systemic exposure for a low-solubility drug. Another such situation is one in which the drug remains amorphous despite extensive efforts to crystallize it. If there is no particular medical benefit, there is less justification for accepting the risks of intentional development of a metastable crystalline or amorphous form. Whether or not there is medical benefit, the risks associated with development of a metastable form must be mitigated by laboratory work which provides assurance that (a) the largest possible form change will have no substantive effect on product quality or bioavailability, and/or (b) a change will not occur under all reasonable real-world storage conditions, and/or (c) analytical methodology and sampling procedures are in place which assure that a problem will be detected before dosage forms which have compromised quality or bioavailability can reach patients.

  13. Pharmacokinetics and dosage regimens of anti-inflammatory drugs.

    PubMed

    Lees, P; May, S A; White, D

    1990-01-01

    The term anti-inflammatory drug, in its broadest sense, encompasses a number of very diverse compounds, ranging from steroids to non-steroidal anti-inflammatory drugs (NSAIDs) and from disease modifying agents (used in the treatment of canine rheumatoid arthritis) to chondroprotective agents (used in the treatment of osteoarthrosis and traumatic arthritis in the horse). For many of these drugs (eg, chondroprotective and disease modifying agents) the mode of action is unknown and even with steroids and NSAIDs there is no universal agreement on mechanism of action. It is therefore in many cases impossible to link pharmacokinetic data to a drug's pharmacodynamics, for example to an effect on a specific biochemical marker. Some agents, including corticosteroids, may have indirect modes of action, so that the pharmacodynamic half-life can be much longer than (and not clearly related to) the pharmacokinetic half-life. In other cases, clinical benefits may only become apparent after several weeks or even months. It can therefore be difficult or impossible to use classical pharmacokinetic approaches to set dosing intervals and dose rates for clinical use. To some extent, the position is more straightforward with NSAIDs. However, even with these drugs simple approaches are not possible and this paper will review briefly some of the studies undertaken in our laboratory which have attempted to utilize NSAID kinetics to set dosage schedules for clinical use.

  14. [Oral dosage forms for children: acceptability and palatability].

    PubMed

    Kojima, Jun

    2015-01-01

    Children generally reject taking medicine which does not have a favorable shape, taste, flavor, etc. However, if a child who needs to take a medicine, rejects taking it, he might never recover from his condition. When a child is unable to take medicine orally, it is intravenously administered, and he and his caregivers then may experience stress. Syrups and suspensions are considered as favorable types of dosage forms in which to orally administer medicine to infants and children. However, they may have disadvantages such as solubility, a bad taste, portability problems or required refrigerator storage. World Health Organization (WHO) currently favors that infants and children be treated with oral solid medicines. New oral solid tablets, such as a mini-tablet, instead of liquid medicines are proposed for this group, however, there are a few reports that mini-tablets are suitable for infants and children. Palatability is one of the main elements of patient acceptability of an oral pediatric medicine. Palatability is defined as the overall appreciation of an oral medicinal product in relation to its smell, taste, aftertaste and feeling in the mouth. Design of the formulation of an oral pediatric medicine should be considered together with its palatability.

  15. Dissolution methodology for taste masked oral dosage forms.

    PubMed

    Gittings, Sally; Turnbull, Neil; Roberts, Clive J; Gershkovich, Pavel

    2014-01-10

    Conventional adult dosage forms are often not suitable for the paediatric and geriatric populations due to either swallowing difficulties or patient repulsion and a requirement for tailored dosing to individual compliance or physiological needs. Alternative formulations are available; however these often require the incorporation of more complex taste masking techniques. One approach to taste masking is to reduce contact between the bitter Active Pharmaceutical Ingredient (API) and oral cavity taste bud regions. This is achieved by hindering release in the oral cavity, or including competitive inhibition of bitter sensation for example by using flavours or sweeteners. There may also be other sensational complications from the API such as residual burning, reflux or metallic taste sensations to deal with. In vitro dissolution testing is employed to elucidate taste masking capability by quantifying release of the drug in simulated oral cavity conditions. Dissolution testing approaches may also be used to potentially predict or quantify the effect of the taste masking technique on the resultant pharmacokinetic profile. The present review investigates the anatomy and physiology of the oral cavity and current approaches to taste masking. In vitro dissolution methodologies adopted in the evaluation of taste masked formulations are discussed for their relative merits and drawbacks. A vast array of methodologies has been employed, with little agreement between approaches, and a lack of biorelevance. Future directions in dissolution methodology such as TNO Intestinal Model (TIM) and the Artificial Stomach and Duodenum model (ASD) are also discussed.

  16. MicroRNAs in genetic disease: rethinking the dosage.

    PubMed

    Henrion-Caude, Alexandra; Girard, Muriel; Amiel, Jeanne

    2012-08-01

    To date, the general assumption was that most mutations interested protein-coding genes only. Thus, only few illustrations have mentioned here that mutations may occur in non-protein coding genes such as microRNAs (miRNAs). We thus report progress in delineating their contribution as phenotypic modulators, genetic switches and fine-tuners of gene expression. We reasoned that browsing their contribution to genetic disease may provide a framework for understanding the proper requirements to devise miRNA-based therapy strategies, in particular the relief of an appropriate dosage. Gain and loss of function of miRNA enforce the need to respectively antagonize or supply the miRNAs. We further categorized human disease according to the different ways in which the miRNA was altered arising either de novo, or inherited whether as a mendelian or as an epistatic trait, uncovering its role in epigenetics. We discuss how improving our knowledge on the contribution of miRNAs to genetic disease may be beneficial to devise appropriate gene therapy strategies.

  17. Mathematical modeling of drug release from lipid dosage forms.

    PubMed

    Siepmann, J; Siepmann, F

    2011-10-10

    Lipid dosage forms provide an interesting potential for controlled drug delivery. In contrast to frequently used poly(ester) based devices for parenteral administration, they do not lead to acidification upon degradation and potential drug inactivation, especially in the case of protein drugs and other acid-labile active agents. The aim of this article is to give an overview on the current state of the art of mathematical modeling of drug release from this type of advanced drug delivery systems. Empirical and semi-empirical models are described as well as mechanistic theories, considering diffusional mass transport, potentially limited drug solubility and the leaching of other, water-soluble excipients into the surrounding bulk fluid. Various practical examples are given, including lipid microparticles, beads and implants, which can successfully be used to control the release of an incorporated drug during periods ranging from a few hours up to several years. The great benefit of mechanistic mathematical theories is the possibility to quantitatively predict the effects of different formulation parameters and device dimensions on the resulting drug release kinetics. Thus, in silico simulations can significantly speed up product optimization. This is particularly useful if long release periods (e.g., several months) are targeted, since experimental trial-and-error studies are highly time-consuming in these cases. In the future it would be highly desirable to combine mechanistic theories with the quantitative description of the drug fate in vivo, ideally including the pharmacodynamic efficacy of the treatments.

  18. Biowaiver monographs for immediate release solid oral dosage forms: isoniazid.

    PubMed

    Becker, C; Dressman, J B; Amidon, G L; Junginger, H E; Kopp, S; Midha, K K; Shah, V P; Stavchansky, S; Barends, D M

    2007-03-01

    Literature data relevant to the decision to allow a waiver of in vivo bioequivalence (BE) testing for the approval of immediate release (IR) solid oral dosage forms containing isoniazid as the only active pharmaceutical ingredient (API) are reviewed. Isoniazid's solubility and permeability characteristics according to the Biopharmaceutics Classification System (BCS), as well as its therapeutic use and therapeutic index, its pharmacokinetic properties, data related to the possibility of excipient interactions and reported BE/bioavailability (BA) problems were taken into consideration. Isoniazid is "highly soluble" but data on its oral absorption and permeability are inconclusive, suggesting this API to be on the borderline of BCS Class I and III. For a number of excipients, an interaction with the permeability is extreme unlikely, but lactose and other deoxidizing saccharides can form condensation products with isoniazid, which may be less permeable than the free API. A biowaiver is recommended for IR solid oral drug products containing isoniazid as the sole API, provided that the test product meets the WHO requirements for "very rapidly dissolving" and contains only the excipients commonly used in isoniazid products, as listed in this article. Lactose and/or other deoxidizing saccharides containing formulations should be subjected to an in vivo BE study.

  19. Biowaiver Monographs for Immediate Release Solid Oral Dosage Forms: Ribavirin.

    PubMed

    Goodarzi, Navid; Barazesh Morgani, Ahmadreza; Abrahamsson, Bertil; Cristofoletti, Rodrigo; Groot, D W; Langguth, Peter; Mehta, Mehul U; Polli, James E; Shah, Vinod P; Dressman, Jennifer B

    2016-04-01

    Literature data relevant to the decision to allow a waiver of in vivo bioequivalence (BE) testing for the approval of immediate release solid oral dosage forms containing ribavirin are reviewed. Ribavirin is highly soluble, but its permeability characteristics are not well defined. Therefore according to the Biopharmaceutical Classification System, and taking a "worst case" approach, ribavirin should be assigned to class III. As ribavirin is transported across the brush border membrane of the human jejunum by hCNT2, it shows saturable uptake in the intestine. However, no common excipients have been shown to compete for ribavirin absorption, nor have problems with BE of immediate release ribavirin formulations containing different excipients and produced by different manufacturing methods been reported in the open literature. So the risk of bioinequivalence caused by these factors appears to be low. Ribavirin is considered a narrow therapeutic index drug, as judged by comparing the minimum effective concentration and minimum toxic concentrations in blood. Although ribavirin would not be eligible for approval via a Biopharmaceutical Classification System-based biowaiver procedure according to today's guidances due to its narrow therapeutic index, the risks of biowaiving should be weighed against the considerable risks associated with studying BE of ribavirin products in healthy subjects.

  20. Biowaiver monographs for immediate release solid oral dosage forms: aciclovir.

    PubMed

    Arnal, J; Gonzalez-Alvarez, I; Bermejo, M; Amidon, G L; Junginger, H E; Kopp, S; Midha, K K; Shah, V P; Stavchansky, S; Dressman, J B; Barends, D M

    2008-12-01

    Literature data relevant to the decision to allow a waiver of in vivo bioequivalence (BE) testing (biowaiver) for the approval of immediate release (IR) solid oral dosage forms containing aciclovir are reviewed. Aciclovir therapeutic use and therapeutic index, pharmacokinetic properties, data related to the possibility of excipient interactions and reported BE/bioavailability (BA) studies were also taken into consideration in order to ascertain whether a biowaiver can be recommended. According to the Biopharmaceutics Classification System (BCS) and considering tablet strengths up to 400 mg, aciclovir would be BCS Class III. However, in some countries also 800 mg tablets are available which fall just within BCS Class IV. Aciclovir seems not to be critical with respect to a risk for bioinequivalence, as no examples of bioinequivalence have been identified. It has a wide therapeutic index and is not used for critical indications. Hence, if: (a) the test product contains only excipients present in aciclovir solid oral IR drug products approved in ICH or associated countries, for instance as presented in this article; and (b) the comparator and the test product both are very rapidly dissolving, a biowaiver for IR aciclovir solid oral drug products is considered justified for all tablet strengths.

  1. Biowaiver monographs for immediate release solid oral dosage forms: lamivudine.

    PubMed

    Strauch, S; Jantratid, E; Dressman, J B; Junginger, H E; Kopp, S; Midha, K K; Shah, V P; Stavchansky, S; Barends, D M

    2011-06-01

    Literature data relevant to the decision to allow a waiver of in vivo bioequivalence (BE) testing for the approval of immediate release (IR) solid oral dosage forms containing lamivudine as the only active pharmaceutical ingredient were reviewed. The solubility and permeability data of lamivudine as well as its therapeutic index, its pharmacokinetic properties, data indicating excipient interactions, and reported BE/bioavailability (BA) studies were taken into consideration. Lamivudine is highly soluble, but its permeability characteristics are not well-defined. Reported BA values in adults ranged from 82% to 88%. Therefore, lamivudine is assigned to the biopharmaceutics classification system (BCS) class III, noting that its permeability characteristics are near the border of BCS class I. Lamivudine is not a narrow therapeutic index drug. Provided that (a) the test product contains only excipients present in lamivudine IR solid oral drug products approved in the International Conference on Harmonization or associated countries in usual amounts and (b) the test product as well as the comparator product fulfills the BCS dissolution criteria for very rapidly dissolving; a biowaiver can be recommended for new lamivudine multisource IR products and major post-approval changes of marketed drug products.

  2. Formulation and evaluation of gastroretentive dosage forms of Clarithromycin.

    PubMed

    Nama, Muralidhar; Gonugunta, Chandra Sekhar Rao; Reddy Veerareddy, Prabhakar

    2008-01-01

    The purpose of this research was to develop the hydrodynamically balanced delivery system of Clarithromycin (CLA) which, after oral administration should have the ability to prolong gastric residence time with the desired in vitro release profile for the localized action in the stomach, in the treatment of Helicobacter pylori (H.pylori) mediated peptic ulcer. By applying wet granulation technique floating tablets of Clarithromycin were prepared. The proportion of sodium bicarbonate was varied to get the least possible lag time, also the polymer part varied to get the desired release. In vivo radiographic studies were performed with Barium sulphate loaded formulation to justify the increased gastric residence time of the dosage form in the stomach, based on the floating principle. The formulation developed using 66.2% Clarithromycin, 12% HPMC K4M polymer, 8% sodium bicarbonate gave floating lag time less than 3 min with a floating time of 12 h, and an in vitro release profile very near to the desired release. X-ray studies showed the enhanced gastric residence time of the tablet to 220 +/- 30 min. The mechanism of release of Clarithromycin from the floating tablets is anomalous diffusion transport and follows zero order kinetics. In vivo radiographic studies suggest that the tablet has increased gastric residence time for the effective localized action of the antibiotic (Clarithromycin) in the treatment of H.pylori mediated peptic ulcer.

  3. Studies of phase transitions in the aripiprazole solid dosage form.

    PubMed

    Łaszcz, Marta; Witkowska, Anna

    2016-01-05

    Studies of the phase transitions in an active substance contained in a solid dosage form are very complicated but essential, especially if an active substance is classified as a BCS Class IV drug. The purpose of this work was the development of sensitive methods for the detection of the phase transitions in the aripiprazole tablets containing initially its form III. Aripiprazole exhibits polymorphism and pseudopolymorphism. Powder diffraction, Raman spectroscopy and differential scanning calorimetry methods were developed for the detection of the polymorphic transition between forms III and I as well as the phase transition of form III into aripiprazole monohydrate in tablets. The study involved the initial 10 mg and 30 mg tablets, as well as those stored in Al/Al blisters, a triplex blister pack and HDPE bottles (with and without desiccant) under accelerated and long term conditions. The polymorphic transition was not observed in the initial and stored tablets but it was visible on the DSC curve of the Abilify(®) 10 mg reference tablets. The formation of the monohydrate was observed in the diffractograms and Raman spectra in the tablets stored under accelerated conditions. The monohydrate phase was not detected in the tablets stored in the Al/Al blisters under long term conditions. The results showed that the Al/Al blisters can be recommended as the packaging of the aripiprazole tablets containing form III.

  4. Suppression of a Lethal Trisomic Phenotype in Drosophila Melanogaster by Increased Dosage of an Unlinked Locus

    PubMed Central

    Dorer, D. R.; Cadden, M. A.; Gordesky-Gold, B.; Harries, G.; Christensen, A. C.

    1993-01-01

    One of the most extreme examples of gene dosage sensitivity is the Triplo-lethal locus (Tpl) on the third chromosome of Drosophila melanogaster, which is lethal when present in either one or three copies. Increased dosage of an unlinked locus, Isis, suppresses the triplo-lethal phenotype of Tpl, but not the haplo-lethal phenotype. We have mapped Isis to the X chromosome region 7E3-8A5, and shown that the suppression is a gene dosage effect. Altered dosage of Isis in the presence of two copies of Tpl has no obvious effects. By examining the interactions between Isis dosage and Tpl we suggest that Isis does not directly repress Tpl expression, but acts downstream on the triplo-lethal phenotype of Tpl. PMID:8514133

  5. Dosage Effects on School Readiness: Evidence from a Randomized Classroom-Based Intervention

    PubMed Central

    Zhai, Fuhua; Raver, C. Cybele; Jones, Stephanie M.; Li-Grining, Christine P.; Pressler, Emily; Gao, Qin

    2016-01-01

    Variations in the dosage of social interventions and the effects of dosage on program outcomes remain understudied. This study examines the dosage effects of the Chicago School Readiness Project, a randomized, multifaceted classroom-based intervention conducted in Head Start settings. Using a principal score matching method to address the issue of selection bias, the study finds that high-dosage levels of teacher training and mental health consultant class visits have larger effects on children’s school readiness than the effects estimated through intention-to-treat (ITT) analyses. Low-dosage levels of treatment are found to have effects that are smaller than those estimated in ITT analyses or to have no statistically significant program effects. Moreover, individual mental health consultation services provided to high-risk children are found to have statistically significant effects on their school readiness. The study discusses the implications of these findings for research and policy. PMID:21488322

  6. Feedback Control of Sex Determination by Dosage Compensation Revealed through Caenorhabditis Elegans Sdc-3 Mutations

    PubMed Central

    DeLong, L.; Plenefisch, J. D.; Klein, R. D.; Meyer, B. J.

    1993-01-01

    In Caenorhabditis elegans, sex determination and dosage compensation are coordinately controlled through a group of genes that respond to the primary sex determination signal. Here we describe a new gene, sdc-3, that also controls these processes. In contrast to previously described genes, the sex determination and dosage compensation activities of sdc-3 are separately mutable, indicating that they function independently. Paradoxically, the sdc-3 null phenotype fails to reveal the role of sdc-3 in sex determination: sdc-3 null mutations that lack both activities disrupt dosage compensation but cause no overt sexual transformation. We demonstrate that the dosage compensation defect of sdc-3 null alleles suppresses their sex determination defect. This self-suppression phenomenon provides a striking example of how a disruption in dosage compensation can affect sexual fate. We propose that the suppression occurs via a feedback mechanism that acts at an early regulatory step in the sex determination pathway to promote proper sexual identity. PMID:8462848

  7. Quantification of sparfloxacin in pharmaceutical dosages and biological samples.

    PubMed

    Shah, Jasmin; Jan, Muhammad Rasul; Khan, Inayatullah; Khan, Muhammad Naeem

    2012-10-01

    A simple and fast method for spectrophotometric determination of sparfloxacin using p-dimethyl-aminobenzaldehyde (DMAB) has been developed. A yellow coloured product formed from reaction between sparfloxacin and DMAB as a result of condensation reaction at room temperature. The maximum absorbance was found at 392 nm with molar absorptivity of 4.9 × 10(3) L mol(-1) cm(-1). All parameters for the reaction, as concentration of DMBA reagent, molarity of sulphuric acid, and reaction temperature were studied. Under the conditions studied, a linear relationship between absorbance of the condensation product and concentration of sparfloxacin in the range of 2.0-80.0 μg mL(-1) was found with good correlation coefficient (0.9997). The limits of detection (LOD) and quantification (LOQ) for the proposed method were found to be 0.22 and 0.75 μg mL(-1) respectively. The repeatability and accuracy (model) of the method was studied at three different concentrations of sparfloxacin and found with value of relative standard deviation less than 2.0%. The method was found selective for determination of sparfloxacin in the presence of commonly used excipients in dosage forms. The developed method was validated statistically and applied successfully to the analysis of the drug in pure form, pharmaceutical preparations, and spiked blood plasma and urine samples with good accuracy (real) and precision. The percentage recovery was found from 99.0-100.0% with relative standard deviation less than 1%. The results of the proposed method were compared statistically with the results of literature HPLC method.

  8. Photostability determination of commercially available nifedipine oral dosage formulations.

    PubMed

    Grundy, J S; Kherani, R; Foster, R T

    1994-12-01

    Nifedipine (NIF), a 1,4-dihydropyridine calcium channel antagonist, undergoes photodegradation to dehydronifedipine (DNIF) upon exposure to ultraviolet (UV) light and to the nitroso analogue of dehydronifedipine (NDNIF) when exposed to sunlight. NIF photodegradation products do not contribute to clinical activity, thus the content of NIF must remain uniform between equipotent formulations. Large differences in light stability between bioequivalent NIF products could potentially result in the therapeutic failure of unstable preparations. Consequently, if large photostability differences do exist between NIF preparations, product substitution may not be warranted. The light stability of 10 intact immediate- or controlled-release oral NIF formulations, obtained from several European and North American manufacturers, was studied using direct continuous artificial sunlight exposure extending over a 12-week period. The content of both NIF and NDNIF for each product was measured to determine the extent of photodecomposition using a specific and sensitive reversed-phase high pressure liquid chromatographic (HPLC) method. In addition, NIF photodegradation was measured using both pure NIF powder and methanolic NIF solution to determine the effectiveness of the artificial sunlight source used in this study. After 12 weeks of artificial sunlight exposure, less than 3% of NDNIF (w/w initial NIF content) was present in each of the 10 tested dosage forms. Photodegradation was greater than 10% (w/w initial NIF content) in approximately 5-10 min (mean t1/2 = 31 min), and in approximately 24 h (mean t1/2 = 7.7 days) of artificial sunlight exposure for methanolic NIF solution and pure NIF powder samples, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

  9. Dosage Comparison of Snake Anti-Venomon Coagulopathy

    PubMed Central

    Rahmani, Ali Hassan; Jalali, Amir; Alemzadeh –Ansari, Mohammad Hassan; Tafazoli, Mina; Rahim, Fakher

    2014-01-01

    This study was done to determine whether high or low dose ofanti-snake venom (ASV) is better incoagulopathy invictims of envenoming by vipers. This retrospective study was conducted on the 154 patients (Mean age ± SD, Range) of viper snake bites who were referred to the emergency ward of Razi Hospital, Ahvaz, Iran over 2 years period (2004-2006).According to the treatment dosage the patients were divided in two groups include group 1(78 cases), low dose regimen and group 2 (76 cases), high dose one. In group 1, the treatment was performed by administration of 4 to 6 vials of ASV through intravenous infusion.In group 2, the patients were given 5 to 10 vials of ASV as an initial dose. In low dose regimen, the number of received packed red blood cell was higher (14 vs. 3) in comparison with high dose group. The number of ASV vials the patients received was 5.5and 21.06 in group 1 and 2, respectively (5.5±1.7 vs. 21.06±10.89; p < 0.01).The difference in frequency of coagulopathy complications, and need for using packed red blood cell were statistically significant(96.2% and 17.9% in group 1 vs. 34.2% and 3.9% in group 2, p < 0.01).It seems that cautious usage of high dose of ASV (10-20 vials) without very special concerns about the cost, dose, and without hazardous side effects is essential for the routine management of sever snake envenoming. PMID:24734082

  10. Optimizing dosage of ketamine and xylazine in murine echocardiography.

    PubMed

    Xu, Qi; Ming, Ziqiu; Dart, Anthony M; Du, Xiao-Jun

    2007-01-01

    1. Ketamine and xylazine (KX) mixture is the most commonly used anaesthetic drug during echocardiography in mice to induce sedation and immobility. Nevertheless, the doses of KX reported in the literature vary substantially with associated significant difference in cardiac function. To explore the optimal KX dosage and observation time for murine echocardiography, we compared the effects of various KX combinations on echocardiographic measurement. 2. Mice were anaesthetized with ketamine (50 or 100 mg/kg) and xylazine (0-10 mg/kg). Echocardiography was performed 5, 10, 20 and 40 min after induction of anaesthesia. Also, cardiac function was assessed in mice with and without pressure-overload induced left ventricle (LV) hypertrophy and dysfunction, either under anaesthesia with KX or whilst conscious. 3. Ketamine at 100 mg/kg alone or together with xylazine at 0.1 mg/kg was associated with a high and stable heart rate (HR), a high fractional shortening (FS) and produced the least effect on LV inner dimension at end of diastole (LVIDd). Ketamine and xylazine at 100 and 10 mg/kg, respectively, produced a lower and stable FS, but with a low and unstable HR. All other combinations resulted in depressed and unstable cardiac function during this period. 4. The dose-dependent suppression of FS by xylazine was counteracted partly by ketamine. 5. Although in the chronic pressure-overload model LV hypertrophy can be detected accurately in both the anaesthetized or conscious state, systolic dysfunction was masked partially by higher doses of xylazine (2.5 or 10 mg/kg) combined with ketamine at 100 mg/kg. 6. With KX anaesthesia, both the dose of xylazine and the anaesthetic duration are critical in achieving an ideal condition for murine echocardiography. Ketamine at 100 mg/kg alone produces acceptable anaesthesia, stable cardiac function with a minimal depressant effect and is therefore recommended if single-dose anaesthetic is to be used.

  11. Effect of aspirin dosage and enteric coating on platelet reactivity.

    PubMed

    Feng, D; McKenna, C; Murillo, J; Mittleman, M A; Gebara, O C; Lipinska, I; Muller, J E; Tofler, G H

    1997-07-15

    Although aspirin is effective in the prevention and treatment of cardiovascular diseases, the optimal dose remains uncertain. The purpose of this study was to compare the platelet inhibitory and prostacyclin-sparing effects of 2 doses (81 and 325 mg) and forms (enteric-coated and regular) of aspirin. Since platelet reactivity has been reported to increase after strenuous exercise, a known trigger of myocardial infarction, subjects were studied following maximal treadmill exercise as well as at rest. Forty male healthy subjects were evaluated using a randomized, double-blind, parallel study design. Blood samples were obtained before and after maximal treadmill exercise at baseline and after 7 days on aspirin therapy. Both enteric and regular aspirin in 81- and 325-mg dosages markedly inhibited adenosine diphosphate and epinephrine-induced aggregation at rest and after exercise. Aspirin also inhibited the platelet response to collagen as assessed by a longer lag time to aggregation. The prolongation of lag time was greater for 325 mg than for 81 mg (100 +/- 7 vs 91 +/- 7; p = 0.04, after exercise). There were no significant dose-related differences in plasma 6-keto-prostaglandin F1alpha level; however, enteric-coated aspirin inhibited the exercise-induced increase in 6-keto-prostaglandin F1alpha to a lesser extent than regular aspirin. Although both doses (81 and 325 mg) and types (regular and enteric-coated) of aspirin inhibited adenosine diphosphate and epinephrine-induced aggregation equally, the 325-mg dose inhibited collagen-induced aggregation to a greater extent than 81 mg. The greater platelet inhibition observed with 325 mg may be clinically relevant in acute coronary syndromes characterized by plaque rupture with extensive collagen exposure and platelet activation.

  12. DU-AGG pilot plant design study

    SciTech Connect

    Lessing, P.A.; Gillman, H.

    1996-07-01

    The Idaho National Engineering Laboratory (INEL) is developing new methods to produce high-density aggregate (artificial rock) primarily consisting of depleted uranium oxide. The objective is to develop a low-cost method whereby uranium oxide powder (UO[sub 2], U[sub 3]O[sub ]8, or UO[sub 3]) can be processed to produce high-density aggregate pieces (DU-AGG) having physical properties suitable for disposal in low-level radioactive disposal facilities or for use as a component of high-density concrete used as shielding for radioactive materials. A commercial company, G-M Systems, conducted a design study for a manufacturing pilot plant to process DU-AGG. The results of that study are included and summarized in this report. Also explained are design considerations, equipment capacities, the equipment list, system operation, layout of equipment in the plant, cost estimates, and the proposed plan and schedule.

  13. Cri du Chat syndrome: a case report.

    PubMed

    Torres, Carolina Paes; Borsatto, Maria Cristina; de Queiroz, Alexandra Mussolino; Lessa, Fernanda Campos Rosetti; Orsi, Iara Agusta

    2005-01-01

    Cri du Chat Syndrome occurs as a result of a partial deletion in the short arm of chromosome 5. Among the consequent abnormalities are low birth weight, a striking catlike cry in infancy, mental retardation, epicanthal folds, hypertelorism and dental malocclusions. This paper presents a case report on the dental treatment of a 23-year-old patient who received multidisciplinary treatment, including special education and precocious stimulation for carriers of this syndrome.

  14. Pourfour Du Petit syndrome after interscalene block

    PubMed Central

    Santhosh, Mysore Chandramouli Basappji; Pai, Rohini B.; Rao, Raghavendra P.

    2013-01-01

    Interscalene block is commonly associated with reversible ipsilateral phrenic nerve block, recurrent laryngeal nerve block, and cervical sympathetic plexus block, presenting as Horner's syndrome. We report a very rare Pourfour Du Petit syndrome which has a clinical presentation opposite to that of Horner's syndrome in a 24-year-old male who was given interscalene block for open reduction and internal fixation of fracture upper third shaft of left humerus. PMID:23956726

  15. Pourfour Du Petit syndrome after interscalene block.

    PubMed

    Santhosh, Mysore Chandramouli Basappji; Pai, Rohini B; Rao, Raghavendra P

    2013-04-01

    Interscalene block is commonly associated with reversible ipsilateral phrenic nerve block, recurrent laryngeal nerve block, and cervical sympathetic plexus block, presenting as Horner's syndrome. We report a very rare Pourfour Du Petit syndrome which has a clinical presentation opposite to that of Horner's syndrome in a 24-year-old male who was given interscalene block for open reduction and internal fixation of fracture upper third shaft of left humerus.

  16. Proprietes de Transport Electronique du Rutile Stoechiometrique

    NASA Astrophysics Data System (ADS)

    Keroack, Danielle

    Le rutile est un oxyde metallique qui presente beaucoup de similitudes avec certains perovskites notamment le titanate de barium ou de strontium. Il est comme ces derniers, compose d'un agencement d'octaedres d'oxygene centres sur l'atome de titane. Ces octaedres sont responsables de la forte polarisabilite de ces cristaux et de leur grande constante dielectrique. Leurs proprietes optiques, seuil d'absorption et spectre de phonons, sont par exemple forts semblables. La presente etude vise a determiner la nature du transport electronique dans le rutile stoechiometrique pur et d'en comparer les resultats avec les proprietes de certains perovskites. Nous determinerons par differentes mesures optoelectroniques les parametres caracteristiques des pieges et leur influence sur le transport des electrons et des trous. Les resultats de conductivite et de capacitance de meme que les spectres de photoconductivite dans nos echantillons ont mis en evidence la presence d'au moins cinq niveaux energetiques dans la bande interdite du rutile agissant comme pieges pour les electrons ou pour les trous et qui jouent un role de premiere importance dans le comportement electrique du rutile. Par la technique de charge transitoire, nous determinerons pour la premiere fois dans le rutile stoechiometrique la grandeur de la mobilite de derive des trous a la temperature ambiante soit 3,4 cm^2/V cdots et nous etablierons une borne superieure a la mobilite des electrons soit 0,1 cm^2 /Vcdots.

  17. Softgels: consumer perceptions and market impact relative to other oral dosage forms.

    PubMed

    Jones, W J; Francis, J J

    2000-01-01

    Softgels, which contain a liquid formulation of a drug, often provide clinical benefit over other solid oral dosage forms and may represent an attractive alternative to them. A consumer preference survey of softgels versus other solid forms investigated four areas: (1) identification of various dosage forms; (2) perception of therapeutic benefit (easiest to swallow, faster-acting, work longer); (3) impact of individual product characteristics on overall product selection; and (4) market impact in terms of premiums consumers would pay on the basis of dosage form. The 300 survey participants strongly preferred clear softgels over other dosage forms in virtually every area. Softgels were perceived as easy to swallow and fast-acting, with a duration of action second only to that of a two-piece capsule. Overall preference was driven by ease of swallowing, and softgels were rated first by the majority of respondents. Consumers would be interested in various products if these were available as softgels rather than in their current oral dosage forms and may be willing to pay a premium for softgel products. This survey confirms consumer preferences for particular dosage forms and for softgels over other solid forms. Pharmaceutical scientists and marketers should consider softgels as alternative dosage forms when developing new compounds or considering life-cycle management of existing products.

  18. Differential replication dynamics for large and small Vibrio chromosomes affect gene dosage, expression and location

    PubMed Central

    Dryselius, Rikard; Izutsu, Kaori; Honda, Takeshi; Iida, Tetsuya

    2008-01-01

    Background Replication of bacterial chromosomes increases copy numbers of genes located near origins of replication relative to genes located near termini. Such differential gene dosage depends on replication rate, doubling time and chromosome size. Although little explored, differential gene dosage may influence both gene expression and location. For vibrios, a diverse family of fast growing gammaproteobacteria, gene dosage may be particularly important as they harbor two chromosomes of different size. Results Here we examined replication dynamics and gene dosage effects for the separate chromosomes of three Vibrio species. We also investigated locations for specific gene types within the genome. The results showed consistently larger gene dosage differences for the large chromosome which also initiated replication long before the small. Accordingly, large chromosome gene expression levels were generally higher and showed an influence from gene dosage. This was reflected by a higher abundance of growth essential and growth contributing genes of which many locate near the origin of replication. In contrast, small chromosome gene expression levels were low and appeared independent of gene dosage. Also, species specific genes are highly abundant and an over-representation of genes involved in transcription could explain its gene dosage independent expression. Conclusion Here we establish a link between replication dynamics and differential gene dosage on one hand and gene expression levels and the location of specific gene types on the other. For vibrios, this relationship appears connected to a polarisation of genetic content between its chromosomes, which may both contribute to and be enhanced by an improved adaptive capacity. PMID:19032792

  19. Practical considerations in development of solid dosage forms that contain cyclodextrin.

    PubMed

    Miller, Lee A; Carrier, Rebecca L; Ahmed, Imran

    2007-07-01

    The following is a review of the literature that addresses the use of cyclodextrin in solid dosage forms. Care was taken to exclude physical and chemical characteristics of cyclodextrin, which have been discussed in the literature. A flow diagram is provided to outline the decision-making steps that are involved in the development process. Both preparation of physical mixtures and inclusion complexes are considered. Analytical techniques to determine the presence of inclusion complexes, the effect of other excipients on complex formation, the effect of size limitation of solid dosages forms, powder processing, and storage of solid dosage forms are discussed.

  20. Sex Chromosome Dosage Compensation in Heliconius Butterflies: Global yet Still Incomplete?

    PubMed

    Walters, James R; Hardcastle, Thomas J; Jiggins, Chris D

    2015-09-02

    The evolution of heterogametic sex chromosomes is often-but not always-accompanied by the evolution of dosage compensating mechanisms that mitigate the impact of sex-specific gene dosage on levels of gene expression. One emerging view of this process is that such mechanisms may only evolve in male-heterogametic (XY) species but not in female-heterogametic (ZW) species, which will consequently exhibit "incomplete" sex chromosome dosage compensation. However, recent results suggest that at least some Lepidoptera (moths and butterflies) may prove to be an exception to this prediction. Studies in bombycoid moths indicate the presence of a chromosome-wide epigenetic mechanism that effectively balances Z chromosome gene expression between the sexes by reducing Z-linked expression in males. In contrast, strong sex chromosome dosage effects without any reduction in male Z-linked expression were previously reported in a pyralid moth, suggesting a lack of any such dosage compensating mechanism. Here we report an analysis of sex chromosome dosage compensation in Heliconius butterflies, sampling multiple individuals for several different adult tissues (head, abdomen, leg, mouth, and antennae). Methodologically, we introduce a novel application of linear mixed-effects models to assess dosage compensation, offering a unified statistical framework that can estimate effects specific to chromosome, to sex, and their interactions (i.e., a dosage effect). Our results show substantially reduced Z-linked expression relative to autosomes in both sexes, as previously observed in bombycoid moths. This observation is consistent with an increasing body of evidence that some lepidopteran species possess an epigenetic dosage compensating mechanism that reduces Z chromosome expression in males to levels comparable with females. However, this mechanism appears to be imperfect in Heliconius, resulting in a modest dosage effect that produces an average 5-20% increase in male expression relative

  1. Relative bioavailability of carbocysteine from three dosage forms, investigated in healthy volunteers.

    PubMed

    Bron, J

    1988-01-01

    The aim of the present study was to evaluate the bioavailability of a new tablet formulation of carbocysteine relative against two other oral carbocysteine containing dosage forms, viz. a syrup and capsules. Plasma levels and urine concentrations of carbocysteine were monitored, following oral administration of all three dosage forms to healthy human volunteers, by direct derivatization of carbocysteine using dabsylchloride and subsequent high performance liquid chromatography. There was no difference in bioavailability of carbocysteine from these dosage forms as expressed by the respective areas under the plasma concentration-time curves and total amounts of unchanged carbocysteine excreted in urine.

  2. Sex Chromosome Dosage Compensation in Heliconius Butterflies: Global yet Still Incomplete?

    PubMed Central

    Walters, James R.; Hardcastle, Thomas J.; Jiggins, Chris D.

    2015-01-01

    The evolution of heterogametic sex chromosomes is often—but not always—accompanied by the evolution of dosage compensating mechanisms that mitigate the impact of sex-specific gene dosage on levels of gene expression. One emerging view of this process is that such mechanisms may only evolve in male-heterogametic (XY) species but not in female-heterogametic (ZW) species, which will consequently exhibit “incomplete” sex chromosome dosage compensation. However, recent results suggest that at least some Lepidoptera (moths and butterflies) may prove to be an exception to this prediction. Studies in bombycoid moths indicate the presence of a chromosome-wide epigenetic mechanism that effectively balances Z chromosome gene expression between the sexes by reducing Z-linked expression in males. In contrast, strong sex chromosome dosage effects without any reduction in male Z-linked expression were previously reported in a pyralid moth, suggesting a lack of any such dosage compensating mechanism. Here we report an analysis of sex chromosome dosage compensation in Heliconius butterflies, sampling multiple individuals for several different adult tissues (head, abdomen, leg, mouth, and antennae). Methodologically, we introduce a novel application of linear mixed-effects models to assess dosage compensation, offering a unified statistical framework that can estimate effects specific to chromosome, to sex, and their interactions (i.e., a dosage effect). Our results show substantially reduced Z-linked expression relative to autosomes in both sexes, as previously observed in bombycoid moths. This observation is consistent with an increasing body of evidence that some lepidopteran species possess an epigenetic dosage compensating mechanism that reduces Z chromosome expression in males to levels comparable with females. However, this mechanism appears to be imperfect in Heliconius, resulting in a modest dosage effect that produces an average 5–20% increase in male expression

  3. Influence du traitement thermique sur l'usinabilite du laiton monophase

    NASA Astrophysics Data System (ADS)

    Cholley, Airy

    La connaissance des proprietes et du comportement d'un materiau en usinage est primordiale pour optimiser son utilisation et obtenir une usinabilite maximale. Dans ce but, l'etude de la modification de la ductilite par traitement thermiques sur plusieurs criteres d'usinabilite tels que les efforts de coupe, la rugosite, les bavures et la formation du copeau a ete menee sur le laiton monophase. A cette fin, l'influence du traitement thermique sur la microstructure du laiton a d'abord ete etudiee. La taille des grains et la durete ont permis de determiner les proprietes mecaniques des etats metallurgiques. Des essais de percage ont ensuite ete effectues sur les etats metallurgiques H01 (99HV), OS100 (88HV) et OS250 (47HV) pour regarder l'influence du traitement thermique sur l'usinabilite. Cette etude experimentale a permis de comprendre l'influence du taux de laminage et de la temperature de recuit sur les proprietes mecaniques. Les essais d'usinabilite ont ensuite permis de prouver que les efforts de coupe sont dependants des conditions de coupe mais pas de la ductilite dans les etats metallurgiques testes. La taille des bavures augmente avec la ductilite et la vitesse de coupe, et diminue avec l'avance. La rugosite de la surface des trous apres l'usinage a egalement ete etudiee. Il a aussi ete prouve par une etude sur les copeaux que la temperature croit avec la vitesse de coupe. L'analyse de la segmentation des copeaux n'a en revanche pas permis de trouver une correlation significative avec les traitements thermiques testes. Enfin, le revetement de l'outil a montre une grande importance sur l'usinabilite du materiau. Il a ete conclu que l'usinabilite du laiton C26000 (CuZn30) est meilleure lorsqu'on travaille dans un etat metallurgique dur. Ces conclusions sont valables pour le laiton monophase etudie, il serait interessant d'examiner aussi le cas des laitons biphases.

  4. Nanocrystals: From Raw Material to the Final Formulated Oral Dosage Form--A Review.

    PubMed

    Scholz, Patrik; Keck, Cornelia M

    2015-01-01

    Many new developed drug actives are poorly soluble, therefore the need to increase the solubility of these actives arises. Nanosuspensions are fast and easy to produce, enhance the bioavailability of poorly soluble drugs and feature many beneficial characteristics. However, nanocrystals in suspension form are physically metastable. Furthermore, the application of nanocrystal suspensions has no retarding effects. To overcome long term stability issues and open up a variety of options for controlled release, nanocrystals can be converted into solid dosage forms by different methods with different outcomes and features. Transformation of nanosuspensions into solid dosage forms opens up manifold options for the development of dosage forms with tailor-made drug release profiles. This review focuses on nanocrystal properties, established and new production techniques, as well as state of the art techniques for transformation of nanosuspensions into solid dosage forms. Nanocrystal technology is already today used in several solid products and holds great potential for future uses.

  5. Effects of fluticasone propionate dosage in an experimental model of feline asthma.

    PubMed

    Cohn, Leah A; DeClue, Amy E; Cohen, Rachael L; Reinero, Carol R

    2010-02-01

    Cats with inflammatory bronchial disease are usually treated with glucocorticoid (GC) drugs to reduce airway inflammation. Inhalant GC delivery can preserve airway effects while systemic effects are minimized. An appropriate dosage regimen for inhaled GC in cats has not been investigated. A blinded, randomized, cross-over study design was used to investigate the ability of three different dosages of the inhalant GC fluticasone propionate delivered by metered dose inhaler to ameliorate eosinophilic airway inflammation in cats with experimentally induced allergic airway inflammation. Further, suppression of the hypothalamic-pituitary-adrenal axis (HPAA) at each dose was assessed. Fluticasone administered at dosages of 44, 110, or 220 microg q 12h reduced airway eosinophilia by 74%, 82%, or 81%, respectively (no difference). None of the dose regimens tested caused HPAA suppression. We conclude that a twice daily dosage of 44 microg fluticasone should be evaluated for the management of cats with naturally occurring inflammatory bronchial disease.

  6. A study on the effects of ozone dosage on dissolved-ozone flotation (DOF) process performance.

    PubMed

    Jin, Xin; Jin, Pengkang; Wang, Xiaochang

    2015-01-01

    Dissolved-ozone flotation (DOF) is a tertiary wastewater treatment process, which combines ozonation and flotation. In this paper, a pilot-scale DOF system fed by secondary effluent from a wastewater treatment plant (WWTP) in China was used to study the effect of ozone dosage on the DOF process performance. The results show that an ozone dosage could affect the DOF performance to a large extent in terms of color and organic matter removal as well as disinfection performance. The optimal color and organic matter removal was achieved at an ozone dosage of 0.8 mg/l. For disinfection, significant improvement in performance could be achieved only when the organic matter removal was optimal. The optimal ozone dosage of at least 1.6 mg/l was put forward, in this case, in order to achieve the optimal color, turbidity, organic matter and disinfection performance.

  7. 75 FR 1274 - Implantation or Injectable Dosage Form New Animal Drugs; Florfenicol and Flunixin

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-01-11

    ... HUMAN SERVICES Food and Drug Administration 21 CFR Part 522 Implantation or Injectable Dosage Form New... veterinary prescription use of a combination injectable solution containing ] florfenicol and flunixin... RESFLOR GOLD (florfenicol and flunixin meglumine), a combination injectable solution, for treatment...

  8. Dosage compensation in Drosophila melanogaster: epigenetic fine-tuning of chromosome-wide transcription.

    PubMed

    Conrad, Thomas; Akhtar, Asifa

    2012-01-18

    Dosage compensation is an epigenetic mechanism that normalizes gene expression from unequal copy numbers of sex chromosomes. Different organisms have evolved alternative molecular solutions to this task. In Drosophila melanogaster, transcription of the single male X chromosome is upregulated by twofold in a process orchestrated by the dosage compensation complex. Despite this conceptual simplicity, dosage compensation involves multiple coordinated steps to recognize and activate the entire X chromosome. We are only beginning to understand the intriguing interplay between multiple levels of local and long-range chromatin regulation required for the fine-tuned transcriptional activation of a heterogeneous gene population. This Review highlights the known facts and open questions of dosage compensation in D. melanogaster.

  9. Presence of XIST specific sequences and apparent failure of X dosage compensation by inactivation in a patient with a severe Turner phenotype and mosaicism for X chromosome abnormalities

    SciTech Connect

    Bent-Williams, A.H.; Felton, S.M.; Driscoll, D.J.

    1994-09-01

    An XIST FISH analysis and a late replication chromosome study was performed for a 10 year old female with Turner stigmata, mental retardation, multiple congenital anomalies and a cytogenetic mosaicism of 45,X,inv(9)(p11q13)/46,X,del(X)(q22),inv(9)(p11q13)/46,X,+mar,inv(9)(p11q13). The X chromosomes from a cell line in which one was deleted for the distal long arm segment (breakpoint of Xq22), observed in 6% of metaphase cells from peripheral blood and 23.3% of metaphase cells from skin fibroblasts, did not demonstrate an asynchronous or differential staining pattern by BrDU techniques. However, both the normal X chromosome and the deleted X chromosome were demonstrated to contain XIST specific sequences by FISH analysis. A very small marker chromosome, observed in 6% of metaphase cells from peripheral blood and 3.3% of metaphase cells from skin fibroblasts, appeared to consist exclusively of X chromosome alpha satellite centromeric material (DXZ1). This finding was consistent with the morphology of the marker chromosome as observed by conventional G-banding. Due to its small size and low level frequency, analysis by late replication BrDU techniques was not possible. The predominate cell line containing a signal X chromosome was observed in 88% of metaphase cells from peripheral blood and 73.3% of metaphase cells from skin fibroblasts. This case is significant because: (1) it represents another case of an X chromosome abnormality in which XIST is apparently present but not expressed; and (2) the more severe phenotype expressed is probably attributable to the failure of X gene dosage compensation by inactivation.

  10. Tumeur brune du maxillaire révélatrice d'hyperparathyroidie primaire: à propos d'un cas et revue de la littérature

    PubMed Central

    Malika, Fassih; Taali, Loubna; Akssim, Mohamed; Reda, Abada; Rouadi, Sami; Mahtar, Mohamed; Roubal, Mohamed; Essaadi, Mustapha; Kadiri, Mohamed Fatmi El

    2013-01-01

    Les tumeurs brunes sont des lésions ostéolytiques rarement révélatrices des hyperparathyroïdies. Elles surviennent habituellement au stade terminal de l'hyperparathyroïdie primaire ou secondaire. Durant les 3 dernières décennies, le diagnostic des hyperparathyroïdies est le plus souvent fait à la phase asymptomatique grâce aux dosages systématiques du calcium et l'avènement des nouvelles techniques, de dosage de la parathormone. Nous rapportons l'observation d'une patiente avec hyperparathyroïdie primaire révélée par une tumeur du maxillaire, dont la TDM avait mis en évidence un processus ostéolytique agressif. L'intervention chirurgicale a consisté en une maxillectomie droite avec reconstruction. Le résultat anatomo-pathologique a conclu en une tumeur à cellule géantes bénigne du maxillaire. Le diagnostic de tumeur brune a été évoqué et confirmé après la réalisation d'un bilan phosphocalcique qui a mis en évidence une hypercalcémie, avec une hypophosphorémie. La recherche étiologique a objectivé à la TDM cervicale un processus en situation rétro et infra thyroïdienne droite en faveur d'un adénome parathyroïdien. Le dosage de la parathormone: 322 pmol/L a confirmé le diagnostic. Nous rappelons à travers cette observation la difficulté d’établir un diagnostic correct chez les patients avec un processus ostéolytique du maxillaire et la nécessité de rechercher une hyperparathyroïdie devant une lésion à cellules géantes vue le caractère insidieux de cette endocrinopathie. PMID:23503933

  11. Evaluation de la fonction hépatique au cours du paludisme grave chez les enfants de moins de cinq ans à Kinshasa en République Démocratique du Congo

    PubMed Central

    Kabamba, Arsène Tshikongo; Mukuku, Olivier; Shamashanga, Laurent Kwete; Kamunga, Daniel Badibanga; Bokanya, Alex Impele; Lukumwena, Zet Kalala; Longanga, Albert Otshudi

    2014-01-01

    Introduction Le paludisme est toujours compté parmi les problèmes de santé publique prioritaires en République Démocratique du Congo suite au nombre de malades et de décès qu'il provoque. Cette étude évalue l'atteinte de la fonction hépatique au cours du paludisme grave chez les enfants de moins de 5 ans. Méthodes Il s'agit d'une étude cas-témoins menée de janvier à juin 2013 à Kinshasa (République Démocratique du Congo) où le dosage des bilirubines totale, directe et indirecte et la mesure de l'activité enzymatique de la Glutamate Pyruvate Transaminase (GPT), de la Glutamate Oxaloacétate Transaminase (GOT) et du taux d'hémoglobine ont été faits chez 46 enfants âgés de moins de 5 ans atteints de paludisme grave (groupe I) et chez 46 autres considérés sains avec une goutte négative (groupe II). Les résultats obtenus ont été comparés dans les deux groupes et le seuil de signification a été fixé à p <0,05. Résultats Les analyses statistiques relèvent que les valeurs sont considérablement élevées en ce qui concerne les deux transaminases (GOT et GPT), la bilirubine directe, la bilirubine indirecte et la bilirubine totale chez les enfants atteints du paludisme grave. Ces analyses montrent une différence significative en défaveur de ces derniers (p < 0,001). Conclusion En effet, cette augmentation des taux plasmatiques des paramètres biologiques analysés observée chez les enfants gravement impaludés traduit ainsi une altération de la fonction hépatique au cours d'un paludisme grave chez l'enfant de moins de cinq ans. PMID:25870721

  12. Complete Dosage Compensation in Anopheles stephensi and the Evolution of Sex-Biased Genes in Mosquitoes

    PubMed Central

    Jiang, Xiaofang; Biedler, James K.; Qi, Yumin; Hall, Andrew Brantley; Tu, Zhijian

    2015-01-01

    Complete dosage compensation refers to hyperexpression of the entire X or Z chromosome in organisms with heterogametic sex chromosomes (XY male or ZW female) in order to compensate for having only one copy of the X or Z chromosome. Recent analyses suggest that complete dosage compensation, as in Drosophila melanogaster, may not be the norm. There has been no systematic study focusing on dosage compensation in mosquitoes. However, analysis of dosage compensation in Anopheles mosquitoes provides opportunities for evolutionary insights, as the X chromosome of Anopheles and that of its Dipteran relative, D. melanogaster formed independently from the same ancestral chromosome. Furthermore, Culicinae mosquitoes, including the Aedes genus, have homomorphic sex-determining chromosomes, negating the need for dosage compensation. Thus, Culicinae genes provide a rare phylogenetic context to investigate dosage compensation in Anopheles mosquitoes. Here, we performed RNA-seq analysis of male and female samples of the Asian malaria mosquito Anopheles stephensi and the yellow fever mosquito Aedes aegypti. Autosomal and X-linked genes in An. stephensi showed very similar levels of expression in both males and females, indicating complete dosage compensation. The uniformity of average expression levels of autosomal and X-linked genes remained when An. stephensi gene expression was normalized by that of their Ae. aegypti orthologs, strengthening the finding of complete dosage compensation in Anopheles. In addition, we comparatively analyzed the differentially expressed genes between adult males and adult females in both species, investigated sex-biased gene chromosomal distribution patterns in An. stephensi and provided three examples where gene duplications may have enabled the acquisition of sex-specific expression during mosquito evolution. PMID:26078263

  13. Ensemble Simulations with Coupled Atmospheric Dynamic and Dispersion Models: Illustrating Uncertainties in Dosage Simulations.

    NASA Astrophysics Data System (ADS)

    Warner, Thomas T.; Sheu, Rong-Shyang; Bowers, James F.; Sykes, R. Ian; Dodd, Gregory C.; Henn, Douglas S.

    2002-05-01

    Ensemble simulations made using a coupled atmospheric dynamic model and a probabilistic Lagrangian puff dispersion model were employed in a forensic analysis of the transport and dispersion of a toxic gas that may have been released near Al Muthanna, Iraq, during the Gulf War. The ensemble study had two objectives, the first of which was to determine the sensitivity of the calculated dosage fields to the choices that must be made about the configuration of the atmospheric dynamic model. In this test, various choices were used for model physics representations and for the large-scale analyses that were used to construct the model initial and boundary conditions. The second study objective was to examine the dispersion model's ability to use ensemble inputs to predict dosage probability distributions. Here, the dispersion model was used with the ensemble mean fields from the individual atmospheric dynamic model runs, including the variability in the individual wind fields, to generate dosage probabilities. These are compared with the explicit dosage probabilities derived from the individual runs of the coupled modeling system. The results demonstrate that the specific choices made about the dynamic-model configuration and the large-scale analyses can have a large impact on the simulated dosages. For example, the area near the source that is exposed to a selected dosage threshold varies by up to a factor of 4 among members of the ensemble. The agreement between the explicit and ensemble dosage probabilities is relatively good for both low and high dosage levels. Although only one ensemble was considered in this study, the encouraging results suggest that a probabilistic dispersion model may be of value in quantifying the effects of uncertainties in a dynamic-model ensemble on dispersion model predictions of atmospheric transport and dispersion.

  14. La reconstruction du sourcil par greffon composite du cuir chevelu: une astuce pour faciliter la technique

    PubMed Central

    El Omari, Mounia; El Mazouz, Samir; Gharib, Noureddine; EL Abbassi, Abdallah

    2015-01-01

    Les sourcils jouent un rôle important dans l’équilibre esthétique du visage. Leur reconstruction ou ophriopoïése, après séquelle de brûlure fait partie intégrante du programme de réhabilitation de la face brûlée. Plusieurs techniques ont été décrites. Nous insistons ici sur l'intérêt d'une technique simple, à la portée de tous les chirurgiens, et dont la méthode et les résultats peuvent être améliorés par un dessin bien planifié des zones donneuse et receveuse: la greffe composite prélevée au niveau du cuir chevelu dessinée à l'aide d'un calque du sourcil controlatéral. PMID:26401195

  15. Suivi après le traitement du cancer du sein

    PubMed Central

    Sisler, Jeffrey; Chaput, Geneviève; Sussman, Jonathan; Ozokwelu, Emmanuel

    2016-01-01

    Résumé Objectif Offrir aux médecins de famille un résumé des recommandations fondées sur les données probantes pour guider les soins aux survivantes traitées pour le cancer du sein. Qualité des données Une recherche documentaire a été effectuée dans MEDLINE entre 2000 et 2016 à l’aide des mots-clés anglais suivants : breast cancer, survivorship, follow-up care, aftercare, guidelines et survivorship care plans, en se concentrant sur la revue des lignes directrices publiées récemment par les organismes nationaux de cancérologie. Les données étaient de niveaux I à III. Message principal Les soins aux survivantes comportent 4 facettes : surveillance et dépistage, prise en charge des effets à long terme, promotion de la santé et coordination des soins. La surveillance des récidives ne se traduit que par une mammographie annuelle, et le dépistage d’autres cancers doit suivre les lignes directrices basées sur la population. La prise en charge des effets à long terme du cancer et de son traitement aborde des problèmes courants tels la douleur, la fatigue, le lymphœdème, la détresse et les effets indésirables des médicaments, de même que les préoccupations à long terme comme la santé du cœur et des os. La promotion de la santé met en relief les bienfaits de l’activité chez les survivantes du cancer, avec l’accent mis sur l’activité physique. Les soins aux survivantes sont de meilleure qualité lorsque divers services et professionnels de la santé participent aux soins, et le médecin de famille joue un rôle important dans la coordination des soins. Conclusion Les médecins de famille sont de plus en plus souvent les principaux fournisseurs de soins de suivi après le traitement du cancer du sein. Le cancer du sein doit être considéré comme une affection médicale chronique, même chez les femmes en rémission, et les patientes profitent de la même approche que celle utilisée pour les autres affections chroniques en

  16. Dosage dependency of intravitreal triamcinolone acetonide as treatment for diabetic macular oedema

    PubMed Central

    Spandau, U H M; Derse, M; Schmitz-Valckenberg, P; Papoulis, C; Jonas, J B

    2005-01-01

    Aim: To evaluate the effect of different doses of intravitreal triamcinolone acetonide on diffuse diabetic macular oedema. Methods: The prospective, randomised, double masked, clinical interventional study included 27 eyes (27 patients) with diffuse diabetic macular oedema. They were randomly divided into three study groups receiving an intravitreal injection of filtered triamcinolone acetonide of about 2 mg (n = 8 eyes), 5 mg (n = 10), or 13 mg (n = 9), respectively. Dosage measurement was performed before filtration. Mean follow up was 6.6 (SD 2.4) months (3–12 months). Main outcome measures were visual acuity and intraocular pressure. Results: Maximal increase in visual acuity was significantly (p = 0.046; 95% CI: 0.032 to 2.99; r = 0.38) correlated with the dosage of intravitreal triamcinolone acetonide. Additionally, the duration of the effect of intravitreal triamcinolone acetonide increased significantly with the dosage of intravitreal triamcinolone acetonide (r = 0.45; p = 0.014). Increase in intraocular pressure during follow up was statistically not significantly associated with the dosage used (p = 0.77). Conclusions: In patients with diffuse diabetic macular oedema receiving intravitreal triamcinolone acetonide, treatment response may last longer and be more pronounced with a dosage of 13 mg than in lower doses of 5 mg or 2 mg. Triamcinolone acetonide induced increase in intraocular pressure may not be markedly associated with the dosage used. PMID:16024853

  17. Dosage effects of Waxy gene on the structures and properties of corn starch.

    PubMed

    Yangcheng, Hanyu; Blanco, Michael; Gardner, Candice; Li, Xuehong; Jane, Jay-Lin

    2016-09-20

    The objective of this study was to understand dosage effects of the Waxy gene on the structures of amylose and amylopectin and on the properties of corn starch. Reciprocal crossing of isogenic normal and waxy corn lines was conducted to develop hybrids with different dosages (0, 1, 2, 3) of Waxy gene in the endosperm. The amylose content of starch and proportions of branch chains of DP 17-30 and extra-long branch chains (DP>100) of amylopectin were positively correlated with the Waxy-gene dosage. Proportions of short (DP<17) and long branch-chains (DP 30-80), however, were negatively correlated with the Waxy-gene dosage. The gelatinization conclusion-temperature and temperature-range of the starch were negatively correlated with the Waxy-gene dosage, indicating that amylose facilitated dissociation of the surrounding crystalline regions. These results helped us understand the function of granule-bound starch synthase I in the biosynthesis of amylose and amylopectin and impacts of Waxy-gene dosages on the properties of corn starch.

  18. Evolution of Dosage Compensation in Anolis carolinensis, a Reptile with XX/XY Chromosomal Sex Determination

    PubMed Central

    Rupp, Shawn M.; Webster, Timothy H.; Olney, Kimberly C.; Hutchins, Elizabeth D.; Kusumi, Kenro

    2017-01-01

    In species with highly heteromorphic sex chromosomes, the degradation of one of the sex chromosomes will result in unequal gene expression between the sexes (e.g. between XX females and XY males) and between the sex chromosomes and the autosomes. Dosage compensation is a process whereby genes on the sex chromosomes achieve equal gene expression. We compared genome-wide levels of transcription between males and females, and between the X chromosome and the autosomes in the green anole, Anolis carolinensis. We present evidence for dosage compensation between the sexes, and between the sex chromosomes and the autosomes. When dividing the X chromosome into regions based on linkage groups, we discovered that genes in the first reported X-linked region, anole linkage group b (LGb), exhibit complete dosage compensation, although the rest of the X-linked genes exhibit incomplete dosage compensation. Our data further suggest that the mechanism of this dosage compensation is upregulation of the X chromosome in males. We report that approximately 10% of coding genes, most of which are on the autosomes, are differentially expressed between males and females. In addition, genes on the X chromosome exhibited higher ratios of nonsynonymous to synonymous substitution than autosomal genes, consistent with the fast-X effect. Our results from the green anole add an additional observation of dosage compensation in a species with XX/XY sex determination. PMID:28206607

  19. Radiation dosage reduction in general dental practice using digital intraoral radiographic systems.

    PubMed

    Hayakawa, Y; Shibuya, H; Ota, Y; Kuroyanagi, K

    1997-02-01

    This report describes the radiation dosage reduction possible in the general dental practice with two CCD (charge-coupled device)-based intraoral radiographic systems: the RVG-S (Trophy Radiologie, Vincennes, France) and the Sens-A-Ray (Regam Medical Systems, Sundsvall, Sweden). Radiation dosages (air-kerma; Gy) necessary for obtaining clinically acceptable images were measured at the cone tip using an ionization chamber type 660-1 (Nuclear Associates, Victoreen, Inc., Carle Place, New York, USA). When the RVG-S was used with an Oramatic 70 (Trophy Radiologie) X-ray generator, dosages at the cone tip ranged from 322 to 612 microGy. These corresponded to 40-60% of the dosages necessary when using Ektaspeed dental X-ray film (Eastman Kodak, Rochester, New York, USA) with a Heliodent 70 (Siemens, Erlangen, Germany) X-ray generator. At 60 kVp, the Sens-A-Ray reduced the dosage in the order of 30% compared with Ektaspeed dental X-ray film. Reduction in radiation dosage is one of the benefits of digital intraoral radiographic systems in general dental clinics. The RVG-S provides greater dose savings than does the Sens-A-Ray.

  20. Applications of Natural Polymeric Materials in Solid Oral Modified-Release Dosage Forms.

    PubMed

    Li, Liang; Zhang, Xin; Gu, Xiangqin; Mao, Shirui

    2015-01-01

    Solid oral modified-release dosage forms provide numerous advantages for drug delivery compared to dosage forms where the drugs are released and absorbed rapidly following ingestion. Natural polymers are of particular interest as drug carriers due to their good safety profile, biocompatibility, biodegradability, and rich sources. This review described the current applications of important natural polymers, such as chitosan, alginate, pectin, guar gum, and xanthan gum, in solid oral modified-release dosage forms. It was shown that natural polymers have been widely used to fabricate solid oral modified-release dosage forms such as matrix tablets, pellets and beads, and especially oral drug delivery systems such as gastroretentive and colon drug delivery systems. Moreover, chemical modifications could overcome the shortcomings associated with the use of natural polymers, and the combination of two or more polymers presented further advantages compared with that of single polymer. In conclusion, natural polymers and modified natural polymers have promising applications in solid oral modified-release dosage forms. However, commercial products based on them are still limited. To accelerate the application of natural polymers in commercial products, in vivo behavior of natural polymers-based solid oral modified-release dosage forms should be deeply investigated, and meanwhile quality of the natural polymers should be controlled strictly, and the influence of formulation and process parameters need to be understood intensively.

  1. A step toward development of printable dosage forms for poorly soluble drugs.

    PubMed

    Raijada, Dhara; Genina, Natalja; Fors, Daniela; Wisaeus, Erik; Peltonen, Jouko; Rantanen, Jukka; Sandler, Niklas

    2013-10-01

    The purpose of this study was to formulate printable dosage forms for a poorly soluble drug (piroxicam; PRX) and to gain understanding of critical parameters to be considered during development of such dosage forms. Liquid formulations of PRX were printed on edible paper using piezoelectric inkjet printing (PIJ) and impression printing (flexography). The printed dosage forms were characterized using scanning electron microscopy with energy dispersive X-ray spectroscopy (SEM-EDX) and the amount of drug was determined using high-performance liquid chromatography. Solutions of PRX in polyethylene glycol 400 (PEG-400):ethanol (40:60) and in PEG-400 were found to be optimal formulations for PIJ and flexography, respectively. SEM-EDX analysis revealed no visible solid particles on the printed dosage forms indicating the drug most likely remained in solution after printing. More accurate drug deposition was obtained by PIJ as compared with flexography. More than 90% drug release was achieved within 5 min regardless of printing method used. The solubility of drug in solvents/cosolvents, rheological properties of formulations, properties of substrate, feasibility and accuracy of the printing methods, and detection limit of analytical techniques for characterization of printed dosage forms are some of the concerns that need to be addressed for development of printable dosage forms of poorly soluble drugs.

  2. Melt-processed polymeric cellular dosage forms for immediate drug release.

    PubMed

    Blaesi, Aron H; Saka, Nannaji

    2015-12-28

    The present immediate-release solid dosage forms, such as the oral tablets and capsules, comprise granular matrices. While effective in releasing the drug rapidly, they are fraught with difficulties inherent in processing particulate matter. By contrast, liquid-based processes would be far more predictable; but the standard cast microstructures are unsuited for immediate-release because they resist fluid percolation and penetration. In this article, we introduce cellular dosage forms that can be readily prepared from polymeric melts by incorporating the nucleation, growth, and coalescence of microscopic gas bubbles in a molding process. We show that the cell topology and formulation of such cellular structures can be engineered to reduce the length-scale of the mass-transfer step, which determines the time of drug release, from as large as the dosage form itself to as small as the thickness of the cell wall. This allows the cellular dosage forms to achieve drug release rates over an order of magnitude faster compared with those of cast matrices, spanning the entire spectrum of immediate-release and beyond. The melt-processed polymeric cellular dosage forms enable predictive design of immediate-release solid dosage forms by tailoring microstructures, and could be manufactured efficiently in a single step.

  3. The Caenorhabditis Elegans Gene Sdc-2 Controls Sex Determination and Dosage Compensation in Xx Animals

    PubMed Central

    Nusbaum, C.; Meyer, B. J.

    1989-01-01

    We have identified a new X-linked gene, sdc-2, that controls the hermaphrodite (XX) modes of both sex determination and X chromosome dosage compensation in Caenorhabditis elegans. Mutations in sdc-2 cause phenotypes that appear to result from a shift of both the sex determination and dosage compensation processes in XX animals to the XO modes of expression. Twenty-eight independent sdc-2 mutations have no apparent effect in XO animals, but cause two distinct phenotypes in XX animals: masculinization, reflecting a defect in sex determination, and lethality or dumpiness, reflecting a disruption in dosage compensation. The dosage compensation defect can be demonstrated directly by showing that sdc-2 mutations cause elevated levels of several X-linked transcripts in XX but not XO animals. While the masculinization is blocked by mutations in sex determining genes required for male development (her-1 and fem-3), the lethality, dumpiness and overexpression of X-linked genes are not, indicating that the effect of sdc-2 mutations on sex determination and dosage compensation are ultimately implemented by two independent pathways. We propose a model in which sdc-2 is involved in the coordinate control of both sex determination and dosage compensation in XX animals and acts in the regulatory hierarchy at a step prior to the divergence of the two pathways. PMID:2759421

  4. Prenatal diagnosis of cri du chat syndrome with encephalocele.

    PubMed

    Bakkum, Jamie N; Watson, William J; Johansen, Keith L; Brost, Brian C

    2005-10-01

    A 19-year-old primigravida was found to have an encephalocele on screening ultrasound study. Amniocentesis indicated cri du chat syndrome, 5p-. Although cri du chat syndrome has been noted in association with central nervous system malformations, encephalocele is a rare finding in this syndrome.

  5. 33 CFR 117.443 - Du Large Bayou.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 33 Navigation and Navigable Waters 1 2013-07-01 2013-07-01 false Du Large Bayou. 117.443 Section 117.443 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY BRIDGES DRAWBRIDGE OPERATION REGULATIONS Specific Requirements Louisiana § 117.443 Du Large Bayou. The draw of...

  6. 33 CFR 117.443 - Du Large Bayou.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 33 Navigation and Navigable Waters 1 2011-07-01 2011-07-01 false Du Large Bayou. 117.443 Section 117.443 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY BRIDGES DRAWBRIDGE OPERATION REGULATIONS Specific Requirements Louisiana § 117.443 Du Large Bayou. The draw of...

  7. 33 CFR 117.443 - Du Large Bayou.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Du Large Bayou. 117.443 Section 117.443 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY BRIDGES DRAWBRIDGE OPERATION REGULATIONS Specific Requirements Louisiana § 117.443 Du Large Bayou. The draw of...

  8. 33 CFR 117.443 - Du Large Bayou.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 33 Navigation and Navigable Waters 1 2014-07-01 2014-07-01 false Du Large Bayou. 117.443 Section 117.443 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY BRIDGES DRAWBRIDGE OPERATION REGULATIONS Specific Requirements Louisiana § 117.443 Du Large Bayou. The draw of...

  9. 33 CFR 117.443 - Du Large Bayou.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 33 Navigation and Navigable Waters 1 2012-07-01 2012-07-01 false Du Large Bayou. 117.443 Section 117.443 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY BRIDGES DRAWBRIDGE OPERATION REGULATIONS Specific Requirements Louisiana § 117.443 Du Large Bayou. The draw of...

  10. Modelisation par elements finis du muscle strie

    NASA Astrophysics Data System (ADS)

    Leonard, Mathieu

    Ce present projet de recherche a permis. de creer un modele par elements finis du muscle strie humain dans le but d'etudier les mecanismes engendrant les lesions musculaires traumatiques. Ce modele constitue une plate-forme numerique capable de discerner l'influence des proprietes mecaniques des fascias et de la cellule musculaire sur le comportement dynamique du muscle lors d'une contraction excentrique, notamment le module de Young et le module de cisaillement de la couche de tissu conjonctif, l'orientation des fibres de collagene de cette membrane et le coefficient de poisson du muscle. La caracterisation experimentale in vitro de ces parametres pour des vitesses de deformation elevees a partir de muscles stries humains actifs est essentielle pour l'etude de lesions musculaires traumatiques. Le modele numerique developpe est capable de modeliser la contraction musculaire comme une transition de phase de la cellule musculaire par un changement de raideur et de volume a l'aide des lois de comportement de materiau predefinies dans le logiciel LS-DYNA (v971, Livermore Software Technology Corporation, Livermore, CA, USA). Le present projet de recherche introduit donc un phenomene physiologique qui pourrait expliquer des blessures musculaires courantes (crampes, courbatures, claquages, etc.), mais aussi des maladies ou desordres touchant le tissu conjonctif comme les collagenoses et la dystrophie musculaire. La predominance de blessures musculaires lors de contractions excentriques est egalement exposee. Le modele developpe dans ce projet de recherche met ainsi a l'avant-scene le concept de transition de phase ouvrant la porte au developpement de nouvelles technologies pour l'activation musculaire chez les personnes atteintes de paraplegie ou de muscles artificiels compacts pour l'elaboration de protheses ou d'exosquelettes. Mots-cles Muscle strie, lesion musculaire, fascia, contraction excentrique, modele par elements finis, transition de phase

  11. Oncoplastie avec conservation mammaire dans le traitement du cancer du sein: à propos de 16 cas

    PubMed Central

    Bouzoubaa, Wail; Laadioui, Meryam; Jayi, Sofia; Alaoui, Fatime Zahra Fdili; Bouguern, Hakima; Chaara, Hikmat; Melhouf, Moulay Abdelilah

    2015-01-01

    Le cancer du sein est actuellement le cancer le plus fréquent chez la femme, et pose un véritable problème diagnostique et thérapeutique. Le dépistage des lésions à un stade de plus en plus précoce, a permis une extension des indications du traitement conservateur radiochirurgical, qui était initialement limitées aux tumeurs de moins de 3 cm, unifocales, non inflammatoires. Par ailleurs, l'utilisation de traitements préopératoires permet d’étendre les indications du traitement conservateur à des tumeurs plus volumineuses. Parallèlement à cette extension des indications de conservation mammaire, on a observé le développement de nouvelles approches thérapeutiques notamment la chirurgie oncoplastique, technique du ganglion sentinelle et chirurgie stéréotaxique, dont les résultats initiaux sont très encouragent. A travers cette étude réalisée dans le service de gynécologie et obstétrique II du CHU HASSAN II de FES au MAROC, après l'analyse rétrospective de 16 patientes traitées par traitement conservateur et oncoplastie, nous avons voulus montrer notre aptitude a réalisé ses techniques chirurgicales et a bien prendre en charge ces patientes, mais aussi évaluer ces techniques en termes de résultat carcinologique et de résultat esthétique, aussi en terme de survie globale, survie sans métastase et en termes de récidive locale entre les plasties mammaires et les traitements usuels: mastectomie et traitement conservateur classique. PMID:26430477

  12. Continuous improvement journey at Du Pont photomasks

    NASA Astrophysics Data System (ADS)

    Henderson, Robert K.

    1994-02-01

    This paper describes the history and experiences of Du Pont Photomasks in their efforts to integrate the continuous improvement philosophy and practices embodied in the Malcolm Baldrige National Quality Award criteria into their way of doing business. A case study of key learnings in this almost four year long process is presented. Specific topics discussed include the process applied to achieve ISO 9000 certification, the quality systems deployed in this effort, and the use of a balanced set of business and quality metrics to assess and improve upon performance.

  13. La fin du jeûne?

    PubMed Central

    Naugler, Christopher; Sidhu, Davinder

    2014-01-01

    Résumé Objectif Présenter une mise à jour sur l’utilité clinique de ne pas être à jeun par rapport à l’être pour l’analyse des lipides dans le but d’améliorer l’observance par les patients, leur sécurité et l’évaluation clinique dans les tests du cholestérol. Qualité des données Les recommandations sont classées comme étant fondées sur des données probantes fortes, acceptables ou faibles (conflictuelles ou insuffisantes), selon les classifications adoptées par le Groupe d’étude canadien sur les soins de santé préventifs. Message principal Le dépistage de la dyslipidémie comme facteur de risque de coronaropathie et la prescription de médicaments hypolipidémiants sont des activités importantes en soins primaires. De récentes données probantes remettent en question la nécessité d’être à jeun pour la mesure des lipides. Dans des études sur la population, le cholestérol total, le cholestérol à lipoprotéines de haute densité et le cholestérol à lipoprotéines autres qu’à haute densité variaient tous d’en moyenne 2 % à jeun. Pour un dépistage de routine, la mesure du cholestérol sans être à jeun est maintenant une option de rechange raisonnable à l’analyse à jeun. Pour les patients diabétiques, l’exigence d’être à jeun peut représenter un important problème de sécurité en raison des possibilités d’hypoglycémie. Pour la surveillance des triglycérides et du cholestérol à lipoprotéines de basse densité chez les patients qui prennent des médicaments hypolipidémiants, le jeûne devient important. Conclusion Être à jeun pour la détermination routinière des niveaux lipidiques est largement inutile et il est improbable que le jeûne influence la stratification du risque clinique chez le patient, tandis que la mesure sans être à jeun pourrait améliorer l’observance par le patient et sa sécurité.

  14. Mesure du taux de la capture radiative du muon par l'hydrogene liquide

    NASA Astrophysics Data System (ADS)

    Jonkmans, Guy

    À basse énergie, l'interaction faible entre leptons et quarks est décrite par une interaction de la forme courant × courant de type V - A. La présence de l'interaction forte induit des couplages additionnels qui doivent être déterminés expérimentalement. De ceux-ci, le couplage pseudoscalaire induit, gp , est mesuré avec la plus grande incertitude et fait l'objet de la présente recherche. L'hypothèse du Courant Axial Partiellement Conservé (CAPC) et l'usage de la relation de Goldberger-Treiman relie gp au couplage axial ga . Cette relation a été vérifiée traditionnellement par la Capture Ordinaire du Muon (COM) à une valeur fixe du moment de transfert q. La Capture Radiative du Muon (CRM), m- p-->nnmg , est un meilleur outil pour l'étude de gp à cause de sa dépendance variable en q2 qui offre une plus grande sensibilité dans la partie à haute énergie du spectre des photons. Toutefois, le petit rapport d'embranchement (~10-8) de la CRM par rapport à la désintégration du muon a retardé cette mesure jusqu'à ce jour. La théorie et les difficultés expérimentales associées à la détection des photons de CRM sont présentées au deuxième chapitre. On décrit ensuite, au troisième chapitre, les composantes du système de détection. Ce détecteur est un spectromètre à paires de grand angle solide (~3p) et qui permet l'observation des photons par l'analyse des électrons et des positrons de photo-conversion. Ainsi, le bruit de fond important des neutrons de la COM ne constitue pas un problème pour cette mesure. Nous décrivons, au quatrième chapitre, toutes les étapes de l'analyse, nécessaires pour la réduction des multiples bruits de fond. Le cinquième chapitre présente le calcul des efficacités ainsi que l'estimation des erreurs systématiques. Le sixième chapitre démontre comment l'on extrait le rapport d'embranchement pour la CRM ainsi que la valeur ae gp . On insiste sur la dépendance de gp en fonction de la valeur de

  15. The Pic du Midi solar survey

    NASA Astrophysics Data System (ADS)

    Koechlin, L.

    2015-12-01

    We carry a long term survey of the solar activity with our coronagraphic system at Pic du Midi de Bigorre in the French Pyrenees (CLIMSO). It is a set of two solar telescopes and two coronagraphs, taking one frame per minute for each of the four channels : Solar disk in H-α (656.28 nm), prominences in H-α, disk in Ca II (393.3 nm), prominences in He I (1083 nm), all year long, weather permitting. Since 2015 we also take images of the FeXIII corona (1074.7 nm) at the rate of one every 10 minutes. These images cover a large field: 1.25 solar diameter, 2k*2K pixels, and are freely downloadable form a database. The improvements made since 2015 concern an autoguiding system for better centering of the solar disk behind the coronagraphic masks, and a new Fe XIII channel at λ=1074.7 nm. In the near future we plan to provide radial velocity maps of the disc and polarimetry maps of the disk and corona. This survey took its present form in 2007 and we plan to maintain image acquisition in the same or better experimental conditions for a long period: one or several solar cycles if possible. During the partial solar eclipse of March 20, 2015, the CLIMSO instruments and the staff at Pic du Midi operating it have provided several millions internet users with real time images of the Sun and Moon during all the phenomenon.

  16. The Epigenome of Evolving Drosophila Neo-Sex Chromosomes: Dosage Compensation and Heterochromatin Formation

    PubMed Central

    Kaiser, Vera B.; Alekseyenko, Artyom A.; Gorchakov, Andrey A.; Bachtrog, Doris

    2013-01-01

    Sex chromosomes originated from autosomes but have evolved a highly specialized chromatin structure. Drosophila Y chromosomes are composed entirely of silent heterochromatin, while male X chromosomes have highly accessible chromatin and are hypertranscribed as a result of dosage compensation. Here, we dissect the molecular mechanisms and functional pressures driving heterochromatin formation and dosage compensation of the recently formed neo-sex chromosomes of Drosophila miranda. We show that the onset of heterochromatin formation on the neo-Y is triggered by an accumulation of repetitive DNA. The neo-X has evolved partial dosage compensation and we find that diverse mutational paths have been utilized to establish several dozen novel binding consensus motifs for the dosage compensation complex on the neo-X, including simple point mutations at pre-binding sites, insertion and deletion mutations, microsatellite expansions, or tandem amplification of weak binding sites. Spreading of these silencing or activating chromatin modifications to adjacent regions results in massive mis-expression of neo-sex linked genes, and little correspondence between functionality of genes and their silencing on the neo-Y or dosage compensation on the neo-X. Intriguingly, the genomic regions being targeted by the dosage compensation complex on the neo-X and those becoming heterochromatic on the neo-Y show little overlap, possibly reflecting different propensities along the ancestral chromosome that formed the sex chromosome to adopt active or repressive chromatin configurations. Our findings have broad implications for current models of sex chromosome evolution, and demonstrate how mechanistic constraints can limit evolutionary adaptations. Our study also highlights how evolution can follow predictable genetic trajectories, by repeatedly acquiring the same 21-bp consensus motif for recruitment of the dosage compensation complex, yet utilizing a diverse array of random mutational changes

  17. Determination of the mechanical properties of solid and cellular polymeric dosage forms by diametral compression.

    PubMed

    Blaesi, Aron H; Saka, Nannaji

    2016-07-25

    At present, the immediate-release solid dosage forms, such as the oral tablets and capsules, are granular solids. They release drug rapidly and have adequate mechanical properties, but their manufacture is fraught with difficulties inherent in processing particulate matter. Such difficulties, however, could be overcome by liquid-based processing. Therefore, we have recently introduced polymeric cellular (i.e., highly porous) dosage forms prepared from a melt process. Experiments have shown that upon immersion in a dissolution medium, the cellular dosage forms with polyethylene glycol (PEG) as excipient and with predominantly open-cell topology disintegrate by exfoliation, thus enabling rapid drug release. If the volume fraction of voids of the open-cell structures is too large, however, their mechanical strength is adversely affected. At present, the common method for determining the tensile strength of brittle, solid dosage forms (such as select granular forms) is the diametral compression test. In this study, the theory of diametral compression is first refined to demonstrate that the relevant mechanical properties of ductile and cellular solids (i.e., the elastic modulus and the yield strength) can also be extracted from this test. Diametral compression experiments are then conducted on PEG-based solid and cellular dosage forms. It is found that the elastic modulus and yield strength of the open-cell structures are about an order of magnitude smaller than those of the non-porous solids, but still are substantially greater than the stiffness and strength requirements for handling the dosage forms manually. This work thus demonstrates that melt-processed polymeric cellular dosage forms that release drug rapidly can be designed and manufactured to have adequate mechanical properties.

  18. Dosage Compensation of the Drosophila White Gene Requires Both the X Chromosome Environment and Multiple Intragenic Elements

    PubMed Central

    Qian, S.; Pirrotta, V.

    1995-01-01

    The X-linked white gene when transposed to autosomes retains only partial dosage compensation. One copy of the gene in males expresses more than one copy but less than two copies in females. When inserted in ectopic X chromosome sites, the mini-white gene of the CaspeR vector can be fully dosage compensated and can even achieve hyperdosage compensation, meaning that one copy in males gives more expression than two copies in females. As sequences are removed gradually from the 5' end of the gene, we observe a progressive transition from hyperdosage compensation to full dosage compensation to partial dosage compensation. When the deletion reaches -17, the gene can no longer dosage compensate fully even on the X chromosome. A deletion reaching +173, 4 bp preceeding the AUG initiation codon, further reduces dosage compensation both on the X chromosome and on autosomes. This truncated gene can still partially dosage compensate on autosomes, indicating the presence of dosage compensation determinants in the protein coding region. We conclude that full dosage compensation requires an X chromosome environment and that the white gene contains multiple dosage-compensation determinants, some near the promoter and some in the coding region. PMID:7713428

  19. Dosage compensation of the Drosophila white gene requires both the X chromosome environment and multiple intragenic elements

    SciTech Connect

    Qian, S.; Pirrotta, V.

    1995-02-01

    The X-linked white gene when transposed to autosomes retains only partial dosage compensation. One copy of the gene in males expresses more than one copy but less than two copies in females. When inserted in ectopic X chromosome sites, the mini-white gene of the CaspeR vector can be fully dosage compensated and can even achieve hyperdosage compensation, meaning that one copy in males gives more expression than two copies in females. As sequences are removed gradually from the 5{prime} end of the gene, we observe a progressive transition from hyperdosage compensation to full dosage compensation to partial dosage compensation. When the deletion reaches -17, the gene can no longer dosage compensate fully even on the X chromosome. A deletion reaching +173, 4 bp preceeding the AUG initiation codon, further reduces dosage compensation both on the X chromosome and on autosomes. This truncated gene can still partially dosage compensate on autosomes, indicating the presence of dosage compensation determinants in the protein coding region. We conclude that full dosage compensation requires an X chromosome environment and that the white gene contains multiple dosage-compensation determinants, some near the promoter and some in the coding region. 48 refs., 4 figs., 2 tabs.

  20. A sequence motif enriched in regions bound by the Drosophila dosage compensation complex

    PubMed Central

    2010-01-01

    Background In Drosophila melanogaster, dosage compensation is mediated by the action of the dosage compensation complex (DCC). How the DCC recognizes the fly X chromosome is still poorly understood. Characteristic sequence signatures at all DCC binding sites have not hitherto been found. Results In this study, we compare the known binding sites of the DCC with oligonucleotide profiles that measure the specificity of the sequences of the D. melanogaster X chromosome. We show that the X chromosome regions bound by the DCC are enriched for a particular type of short, repetitive sequences. Their distribution suggests that these sequences contribute to chromosome recognition, the generation of DCC binding sites and/or the local spreading of the complex. Comparative data indicate that the same sequences may be involved in dosage compensation in other Drosophila species. Conclusions These results offer an explanation for the wild-type binding of the DCC along the Drosophila X chromosome, contribute to delineate the forces leading to the establishment of dosage compensation and suggest new experimental approaches to understand the precise biochemical features of the dosage compensation system. PMID:20226017

  1. Post-Translational Dosage Compensation Buffers Genetic Perturbations to Stoichiometry of Protein Complexes.

    PubMed

    Ishikawa, Koji; Makanae, Koji; Iwasaki, Shintaro; Ingolia, Nicholas T; Moriya, Hisao

    2017-01-01

    Understanding buffering mechanisms for various perturbations is essential for understanding robustness in cellular systems. Protein-level dosage compensation, which arises when changes in gene copy number do not translate linearly into protein level, is one mechanism for buffering against genetic perturbations. Here, we present an approach to identify genes with dosage compensation by increasing the copy number of individual genes using the genetic tug-of-war technique. Our screen of chromosome I suggests that dosage-compensated genes constitute approximately 10% of the genome and consist predominantly of subunits of multi-protein complexes. Importantly, because subunit levels are regulated in a stoichiometry-dependent manner, dosage compensation plays a crucial role in maintaining subunit stoichiometries. Indeed, we observed changes in the levels of a complex when its subunit stoichiometries were perturbed. We further analyzed compensation mechanisms using a proteasome-defective mutant as well as ribosome profiling, which provided strong evidence for compensation by ubiquitin-dependent degradation but not reduced translational efficiency. Thus, our study provides a systematic understanding of dosage compensation and highlights that this post-translational regulation is a critical aspect of robustness in cellular systems.

  2. Post-Translational Dosage Compensation Buffers Genetic Perturbations to Stoichiometry of Protein Complexes

    PubMed Central

    Makanae, Koji; Iwasaki, Shintaro; Moriya, Hisao

    2017-01-01

    Understanding buffering mechanisms for various perturbations is essential for understanding robustness in cellular systems. Protein-level dosage compensation, which arises when changes in gene copy number do not translate linearly into protein level, is one mechanism for buffering against genetic perturbations. Here, we present an approach to identify genes with dosage compensation by increasing the copy number of individual genes using the genetic tug-of-war technique. Our screen of chromosome I suggests that dosage-compensated genes constitute approximately 10% of the genome and consist predominantly of subunits of multi-protein complexes. Importantly, because subunit levels are regulated in a stoichiometry-dependent manner, dosage compensation plays a crucial role in maintaining subunit stoichiometries. Indeed, we observed changes in the levels of a complex when its subunit stoichiometries were perturbed. We further analyzed compensation mechanisms using a proteasome-defective mutant as well as ribosome profiling, which provided strong evidence for compensation by ubiquitin-dependent degradation but not reduced translational efficiency. Thus, our study provides a systematic understanding of dosage compensation and highlights that this post-translational regulation is a critical aspect of robustness in cellular systems. PMID:28121980

  3. The Role of Solid State Characterization in Predicting Stability of Solid Dosage Forms.

    PubMed

    Szabó, Péter; Zelko, Romána; Antal, István

    2016-01-01

    Stability of a dosage form is its ability to preserve its quality attributes within preset limits. The time span over which these attributes remain within specifications is the shelf-life of the drug product. Stability is a very complex feature and is influenced not only by the stability of the drug substance but also by the stability of excipients and the interaction of the components within the system. Another important contributing factor is the packaging material, which is responsible for the protection of the drug product. Not only drug substances, but also excipients are susceptible to different degradation mechanisms. Amorphous polymers, a relatively frequently used group of excipients, are especially prone to physical instability. Through the process of physical ageing, a slow volume and enthalpy relaxation can be experienced, which can lead to remarkable alterations in solid dosage form properties. Functional changes within the solid dosage form associated with instability include changes in mechanical properties, homogeneity and drug release characteristics, discoloration, phase separation or changes in melting time of suppositories. Stability assessment is a crucial issue during formulation development, which is strictly regulated by authorities responsible for drug registration. The primary purpose of this paper is to give an overview of the different types of physical changes influencing solid state stability of dosage forms, and how such changes can be monitored. We will also illustrate how the quality of a solid dosage form varies with time under the influence of different environmental factors.

  4. Exon dosage analysis of parkin gene in Chinese sporadic Parkinson's disease.

    PubMed

    Guo, Ji-Feng; Dong, Xiao-Li; Xu, Qian; Li, Nan; Yan, Xin-Xiang; Xia, Kun; Tang, Bei-Sha

    2015-09-14

    Parkin gene mutations are by far the most common mutations in both familial Parkinson's disease (PD) and sporadic PD. Approximately, 50% of parkin mutations is exon dosage mutations (i.e., deletions and duplications of entire exons). Here, we first established a MLPA assay for quick detection of parkin exon rearrangements. Then, we studied parkin exon dosage mutations in 755 Chinese sporadic PDdisease patients using the established MLPA assay. We found that there were 25 (3.3%) patients with exon dosage alterations including deletions and duplications, 20 (11.4%) patients with exon rearrangements in 178 early-onset patients, and 5 (0.86%) patients with exon rearrangement mutations in 579 later-onset patients. The percentage of individuals with parkin dosage mutations is more than 33% when the age at onset is less than 30 years old, but less than 7% when the age at onset is more than 30. In these mutations, deletion is the main mutational style, especially in exon 2-5. Our results indicated that exon dosage mutations in parkin gene might be the main cause for sporadic PD, especially in EOP.

  5. Compensatory Drift and the Evolutionary Dynamics of Dosage-Sensitive Duplicate Genes.

    PubMed

    Thompson, Ammon; Zakon, Harold H; Kirkpatrick, Mark

    2016-02-01

    Dosage-balance selection preserves functionally redundant duplicates (paralogs) at the optimum for their combined expression. Here we present a model of the dynamics of duplicate genes coevolving under dosage-balance selection. We call this the compensatory drift model. Results show that even when strong dosage-balance selection constrains total expression to the optimum, expression of each duplicate can diverge by drift from its original level. The rate of divergence slows as the strength of stabilizing selection, the size of the mutation effect, and/or the size of the population increases. We show that dosage-balance selection impedes neofunctionalization early after duplication but can later facilitate it. We fit this model to data from sodium channel duplicates in 10 families of teleost fish; these include two convergent lineages of electric fish in which one of the duplicates neofunctionalized. Using the model, we estimated the strength of dosage-balance selection for these genes. The results indicate that functionally redundant paralogs still may undergo radical functional changes after a prolonged period of compensatory drift.

  6. Reduction of Radiation Dosage in Visualization of Paranasal Sinuses in Daily Routine

    PubMed Central

    Diogo, Isabell; Leicht, Julia; Mandapathil, Magis; Wilhelm, Thomas; Teymoortash, Afshin; Jahns, Evelyn

    2017-01-01

    Background. Preoperative imaging of the nose and paranasal sinus is standard in otorhinolaryngology. Previous studies on phantoms demonstrated the potential for dose reduction of cone beam computed tomography (CBCT) by varying the application parameters. Methodology. Based on previous studies, the standard protocol of paranasal sinus imaging by CBCT was altered. One hundred and fifty examinations using the old protocol (01/2010–01/2011, high dosage) and 150 examinations using the new protocol (09/2012–09/2013, low dosage) were evaluated and compared for the visibility of 17 anatomical structures, the Lund-Mackay Score, and technical parameters. Results. Alteration of the protocol resulted in a significant reduction in dosage (6.64 mGy versus 2.88 mGy). Both groups showed the same amount of pathology (Lund-Mackay Score: 4.95 ± 3.79 versus 5.26 ± 5.77; p = 0.558). There was a significant better visibility of the anatomical structures (all visible = 1, nothing visible = 4) (results: 1.25 versus 1.17; p = 0.001) in the low-dosage group. Conclusion. Despite a significant reduction in the applied dosage, reliable visualization of the bony anatomy of the anterior skull base is possible by CBCT. This demonstrates the need for the discussion of the required clinical imaging quality. PMID:28255303

  7. Manufacturing Solid Dosage Forms from Bulk Liquids Using the Fluid-bed Drying Technology.

    PubMed

    Qi, Jianping; Lu, Y I; Wu, Wei

    2015-01-01

    Solid dosage forms are better than liquid dosage forms in many ways, such as improved physical and chemical stability, ease of storage and transportation, improved handling properties, and patient compliance. Therefore, it is required to transform dosage forms of liquid origins into solid dosage forms. The functional approaches are to absorb the liquids by solid excipients or through drying. The conventional drying technologies for this purpose include drying by heating, vacuum-, freeze- and spray-drying, etc. Among these drying technologies, fluidbed drying emerges as a new technology that possesses unique advantages. Fluid-bed drying or coating is highly efficient in solvent removal, can be performed at relatively low temperatures, and is a one-step process to manufacture formulations in pellet forms. In this article, the status of the art of manufacturing solid dosage forms from bulk liquids by fluid-bed drying technology was reviewed emphasizing on its application in solid dispersion, inclusion complexes, self-microemulsifying systems, and various nanoscale drug delivery systems.

  8. Pharmaceutical approaches to preparing pelletized dosage forms using the extrusion-spheronization process.

    PubMed

    Trivedi, Namrata R; Rajan, Maria Gerald; Johnson, James R; Shukla, Atul J

    2007-01-01

    Pelletized dosage forms date back to the 1950s, when the first product was introduced to the market. Since then, these dosage forms have gained considerable popularity because of their distinct advantages, such as ease of capsule filling because of better flow properties of the spherical pellets; enhancement of drug dissolution; ease of coating; sustained, controlled, or site-specific delivery of the drug from coated pellets; uniform packing; even distribution in the GI tract; and less GI irritation. Pelletized dosage forms can be prepared by a number of techniques, including drug layering on nonpareil sugar or microcrystalline cellulose beads, spray drying, spray congealing, rotogranulation, hot-melt extrusion, and spheronization of low melting materials or extrusion-spheronization of a wet mass. This review discusses recent developments in the pharmaceutical approaches that have been used to prepare pelletized dosage forms using the extrusion-spheronization process over the last decade. The review is divided into three parts: the first part discusses the extrusion-spheronization process, the second part discusses the effect of varying formulation and process parameters on the properties of the pellets, and the last part discusses the different approaches that have been used to prepare pelletized dosage forms using the extrusion-spheronization process.

  9. Effects of pharmaceutical processing on pepsin activity during the formulation of solid dosage forms.

    PubMed

    Kristó, Katalin; Pintye-Hódi, Klára

    2013-02-01

    The main aim of this study was to investigate the effects of pharmaceutical technological methods on pepsin activity during the formulation of solid dosage forms. The circumstances of direct compression and wet granulation were modeled. During direct compression, the heat and the compression force must be taken into consideration. The effects of these parameters were investigated in three materials (pure pepsin, and 1:1 (w/w) pepsin-tartaric acid and 1:1 (w/w) pepsin-citric acid powder mixtures). It was concluded that direct compression is appropriate for the formulation of solid dosage forms containing pepsin through application without acids or with acids at low compression force. The effects of wet granulation were investigated with a factorial design for the same three materials. The factors were time, temperature and moisture content. There was no significant effect of the factors when acids were not applied. Temperature was a significant factor when acids were applied. The negative effect was significantly higher for citric acid than for tartaric acid. It was found that wet granulation can be utilized for the processing of pepsin into solid dosage forms under well-controlled circumstances. The application of citric acid is not recommended during the formulation of solid dosage forms through wet granulation. A mathematically based optimization may be necessary for preformulation studies of the preparation of dosage forms containing sensitive enzymes.

  10. Novel delivery device for monolithical solid oral dosage forms for personalized medicine.

    PubMed

    Wening, Klaus; Breitkreutz, Jörg

    2010-08-16

    There is an evident need for solid oral dosage forms allowing patients' tailor-made dosing due to variations in metabolization or small therapeutic indexes of drug substances. The objective of this work is the development of a device equipped with a novel solid dosage form, containing carvedilol as model drug, for the delivery of monolithical drug carriers in individual doses. The device was developed and constructed enabling an exact feed rate and dose adjustment by a cutting mechanism. A twin-screw extruder was used for producing cylindrical solid dosage forms. Divided doses were characterized by mass variation, cutting behavior and drug dissolution in order to investigate their applicability for practical use. Different formulations could be extruded obtaining straight cylindrical rods, which are divisible in exact slices by using the novel device. Forces below 20 N were needed to divide doses which comply with pharmacopoeial specification "conformity of mass". The developed formulations exhibit a sustained release of carvedilol within a range from 7 up to 16 h. A novel system consisting of a device and a cylindrical dosage form was developed. Patients' individual doses can be applied as monolithical solid dosage forms for oral use.

  11. Effects of Web-Based Instruction on Nursing Students' Arithmetical and Drug Dosage Calculation Skills.

    PubMed

    Karabag Aydin, Arzu; Dinç, Leyla

    2016-12-29

    Drug dosage calculation skill is critical for all nursing students to ensure patient safety, particularly during clinical practice. The study purpose was to evaluate the effectiveness of Web-based instruction on improving nursing students' arithmetical and drug dosage calculation skills using a pretest-posttest design. A total of 63 nursing students participated. Data were collected through the Demographic Information Form, and the Arithmetic Skill Test and Drug Dosage Calculation Skill Test were used as pre and posttests. The pretest was conducted in the classroom. A Web site was then constructed, which included audio presentations of lectures, quizzes, and online posttests. Students had Web-based training for 8 weeks and then they completed the posttest. Pretest and posttest scores were compared using the Wilcoxon test and correlation coefficients were used to identify the relationship between arithmetic and calculation skills scores. The results demonstrated that Web-based teaching improves students' arithmetic and drug dosage calculation skills. There was a positive correlation between the arithmetic skill and drug dosage calculation skill scores of students. Web-based teaching programs can be used to improve knowledge and skills at a cognitive level in nursing students.

  12. Adrenal Insufficiency under Standard Dosage of Glucocorticoid Replacement after Unilateral Adrenalectomy for Cushing's Syndrome

    PubMed Central

    Fujii, Kentaro; Kurihara, Isao; Hiratsuka, Ken; Sato, Seiji; Yokota, Kenichi; Kobayashi, Sakiko; Shibata, Hirotaka; Itoh, Hiroshi

    2016-01-01

    Glucocorticoid replacement is needed for patients after adrenal surgery for Cushing's syndrome; however, the adequate dosage is not easily determined. The patient was a 62-year-old woman who has had hypertension for 5 years and presented with heart failure due to hypertrophic cardiomyopathy. She consulted with us because of general fatigue, facial edema, and muscle weakness and was diagnosed with Cushing's syndrome. A laparoscopic left adrenalectomy was performed, standard dosage of postoperative replacement was administered, and she was discharged with 30 mg/day of hydrocortisone (cortisol). However, she suffered from loss of appetite and was transferred to an emergency unit with the symptoms of adrenal insufficiency on postoperative day 15. After initial hydrocortisone replacement with 200 mg/day, the dosage was gradually decreased during hospitalization; however, reduction of hydrocortisone dosage lower than 60 mg/day was difficult because of nausea and fatigue. Her circadian cortisol profile after hydrocortisone administration showed delayed and lowered peaks, which suggested that hydrocortisone absorption in the intestine was impaired. Therefore, complicated heart failure may have led to the adrenal insufficiency in the patient. In such cases, we should consider postoperative administration of more than the standard dosage of hydrocortisone to avoid adrenal insufficiency after surgery for Cushing's syndrome. PMID:27375907

  13. Dosage-dependent non-linear effect of L-dopa on human motor cortex plasticity.

    PubMed

    Monte-Silva, Katia; Liebetanz, David; Grundey, Jessica; Paulus, Walter; Nitsche, Michael A

    2010-09-15

    The neuromodulator dopamine affects learning and memory formation and their likely physiological correlates, long-term depression and potentiation, in animals and humans. It is known from animal experiments that dopamine exerts a dosage-dependent, inverted U-shaped effect on these functions. However, this has not been explored in humans so far. In order to reveal a non-linear dose-dependent effect of dopamine on cortical plasticity in humans, we explored the impact of 25, 100 and 200 mg of L-dopa on transcranial direct current (tDCS)-induced plasticity in twelve healthy human subjects. The primary motor cortex served as a model system, and plasticity was monitored by motor evoked potential amplitudes elicited by transcranial magnetic stimulation. As compared to placebo medication, low and high dosages of L-dopa abolished facilitatory as well as inhibitory plasticity, whereas the medium dosage prolonged inhibitory plasticity, and turned facilitatory plasticity into inhibition. Thus the results show clear non-linear, dosage-dependent effects of dopamine on both facilitatory and inhibitory plasticity, and support the assumption of the importance of a specific dosage of dopamine optimally suited to improve plasticity. This might be important for the therapeutic application of dopaminergic agents, especially for rehabilitative purposes, and explain some opposing results in former studies.

  14. Brain stem hypoplasia associated with Cri-du-Chat syndrome.

    PubMed

    Hong, Jin Ho; Lee, Ha Young; Lim, Myung Kwan; Kim, Mi Young; Kang, Young Hye; Lee, Kyung Hee; Cho, Soon Gu

    2013-01-01

    Cri-du-Chat syndrome, also called the 5p-syndrome, is a rare genetic abnormality, and only few cases have been reported on its brain MRI findings. We describe the magnetic resonance imaging findings of a 1-year-old girl with Cri-du-Chat syndrome who showed brain stem hypoplasia, particularly in the pons, with normal cerebellum and diffuse hypoplasia of the cerebral hemispheres. We suggest that Cri-du-Chat syndrome chould be suspected in children with brain stem hypoplasia, particularly for those with high-pitched cries.

  15. Brain Stem Hypoplasia Associated with Cri-du-Chat Syndrome

    PubMed Central

    Hong, Jin Ho; Lim, Myung Kwan; Kim, Mi Young; Kang, Young Hye; Lee, Kyung Hee; Cho, Soon Gu

    2013-01-01

    Cri-du-Chat syndrome, also called the 5p-syndrome, is a rare genetic abnormality, and only few cases have been reported on its brain MRI findings. We describe the magnetic resonance imaging findings of a 1-year-old girl with Cri-du-Chat syndrome who showed brain stem hypoplasia, particularly in the pons, with normal cerebellum and diffuse hypoplasia of the cerebral hemispheres. We suggest that Cri-du-Chat syndrome chould be suspected in children with brain stem hypoplasia, particularly for those with high-pitched cries. PMID:24265573

  16. Developmental and behavioural characteristics of cri du chat syndrome.

    PubMed Central

    Cornish, K M; Pigram, J

    1996-01-01

    Developmental and behavioural characteristics were assessed in 27 children with cri du chat syndrome using the Society for the Study of Behavioural Phenotypes questionnaire, which gave information on prenatal and perinatal conditions, neurological problems, and developmental and behavioural difficulties. The findings suggest that the behavioural profile of children with cri du chat syndrome incorporates self injurious behaviour, repetitive movements, hypersensitivity to sound, clumsiness, and obsessive attachments to objects. In terms of a developmental profile, children with cri du chat syndrome were able to communicate their needs, socially interact with others, and have some degree of mobility. PMID:8957962

  17. Genome-Wide Gene/Genome Dosage Imbalance Regulates Gene Expressions in Synthetic Brassica napus and Derivatives (AC, AAC, CCA, CCAA)

    PubMed Central

    Tan, Chen; Pan, Qi; Cui, Cheng; Xiang, Yi; Ge, Xianhong; Li, Zaiyun

    2016-01-01

    Gene/genome dosage balance is an essential evolutionary mechanism for organisms to ensure a normal function, but the underlying causes of dosage-imbalance regulation remain poorly understood. Herein, the serial Brassica hybrids/polyploids (AC, AAC, CCA, CCAA) with different copies of A and C subgenomes from the same two parents of Brassica rapa and Brassica oleracea were synthesized to investigate the effects of genome dosages on gene expressions and interactions by using RNA-Seq. The expression changes of A- and C-subgenome genes were consistent with dosage alterations. Dosage-dependent and -independent genes were grouped according to the correlations between dosage variations and gene expressions. Expression levels of dosage-dependent genes were strongly correlated with dosage changes and mainly contributed to dosage effects, while those of dosage-independent genes gave weak correlations with dosage variations and mostly facilitated dosage compensation. More protein–protein interactions were detected for dosage-independent genes than dosage-dependent ones, as predicted by the dosage balance hypothesis. Dosage-dependent genes more likely impacted the expressions by trans effects, whereas dosage-independent genes preferred to play by cis effects. Furthermore, dosage-dependent genes were mainly associated with the basic biological processes to maintain the stability of the growth and development, while dosage-independent genes were more enriched in the stress response related processes to accelerate adaptation. The present comprehensive analysis of gene expression dependent/independent on dosage alterations in Brassica polyploids provided new insights into gene/genome dosage-imbalance regulation of gene expressions. PMID:27721820

  18. Genome-Wide Gene/Genome Dosage Imbalance Regulates Gene Expressions in Synthetic Brassica napus and Derivatives (AC, AAC, CCA, CCAA).

    PubMed

    Tan, Chen; Pan, Qi; Cui, Cheng; Xiang, Yi; Ge, Xianhong; Li, Zaiyun

    2016-01-01

    Gene/genome dosage balance is an essential evolutionary mechanism for organisms to ensure a normal function, but the underlying causes of dosage-imbalance regulation remain poorly understood. Herein, the serial Brassica hybrids/polyploids (AC, AAC, CCA, CCAA) with different copies of A and C subgenomes from the same two parents of Brassica rapa and Brassica oleracea were synthesized to investigate the effects of genome dosages on gene expressions and interactions by using RNA-Seq. The expression changes of A- and C-subgenome genes were consistent with dosage alterations. Dosage-dependent and -independent genes were grouped according to the correlations between dosage variations and gene expressions. Expression levels of dosage-dependent genes were strongly correlated with dosage changes and mainly contributed to dosage effects, while those of dosage-independent genes gave weak correlations with dosage variations and mostly facilitated dosage compensation. More protein-protein interactions were detected for dosage-independent genes than dosage-dependent ones, as predicted by the dosage balance hypothesis. Dosage-dependent genes more likely impacted the expressions by trans effects, whereas dosage-independent genes preferred to play by cis effects. Furthermore, dosage-dependent genes were mainly associated with the basic biological processes to maintain the stability of the growth and development, while dosage-independent genes were more enriched in the stress response related processes to accelerate adaptation. The present comprehensive analysis of gene expression dependent/independent on dosage alterations in Brassica polyploids provided new insights into gene/genome dosage-imbalance regulation of gene expressions.

  19. Un cas de fracture luxation négligée du coude avec conservation de la fonction du coude

    PubMed Central

    Lahrach, Kamal; Ammoumri, Oussama; Mezzani, Amine; Benabid, Mounir; Marzouki, Amine; Boutayeb, Fawzi

    2015-01-01

    Les fractures luxations du coude sont rares et souvent mal tolérées chez les sujets jeunes actifs. Nous rapportons un cas de fracture-luxation du coude remontant à 20 ans. C'est un jeune de 35 ans, victime il y a 20 ans d'un traumatisme fermé, suite à une chute lors d'un match du football, de son coude gauche occasionnant une fracture-luxation du coude. Le patient a refusé une intervention chirurgicale avec une auto-rééducation. L'examen a mis en évidence une conservation de la fonction du coude. Un bilan radiologique a montré une fracture luxation du coude avec remaniement de la palette humérale. Une abstention thérapeutique a été décidée devant l'ancienneté de la fracture-luxation et la gêne fonctionnelle minime engendrée. Contrairement aux autres séries, la fracture-luxation dans notre cas était bien tolérée malgré le jeune âge du patient. PMID:26113930

  20. MRI as a tool for evaluation of oral controlled release dosage forms.

    PubMed

    Dorożyński, Przemysław P; Kulinowski, Piotr; Młynarczyk, Anna; Stanisz, Greg J

    2012-02-01

    The magnetic resonance imaging (MRI) studies of controlled-release (CR) dosage forms can be roughly divided into two groups. The first comprises studies performed in static conditions (small solvent volumes and ambient temperature). Such studies have provided insight into molecular phenomena in hydrating polymeric matrices. The second group covers research performed in dynamic conditions (medium flow or stirring) related to drug dissolution. An important issue is supplementation of the MRI results with data obtained by complementary techniques, such as X-ray microtomography (μCT). As we discuss here, an understanding of the mechanism underlying the release of the drug from the dosage form will lead to the development of detailed, molecularly defined, CR dosage forms.

  1. Dominance and gene dosage balance in health and disease: why levels matter!

    PubMed

    Veitia, Reiner A; Birchler, James A

    2010-01-01

    The classical concept of genetic dominance is a simplification of a more quantitative reality. This is clearly exemplified by aneuploid syndromes, of which the best known case is trisomy 21. Moreover, there is an increasing number of clinical conditions due to reduced dosage (haploinsufficiency) of genes encoding transcription factors and other proteins involved in signal transduction and macromolecular complexes. In such genetic diseases, a high degree of phenotypic variability is observed, which calls for an explanation. The sources of dominance are heterogeneous and difficult to cover in a brief review. Here, we will focus on the molecular bases of dosage-sensitive syndromes from the perspective of the gene dosage balance hypothesis, which postulates that stoichiometric alterations of macromolecular complexes or cellular networks are responsible for dominant phenotypes, because of the existing non-linear relationships between the genotypic and phenotypic values with which they are associated.

  2. Effect of Calcium Ions on the Disintegration of Enteric-Coated Solid Dosage Forms.

    PubMed

    Al-Gousous, Jozef; Langguth, Peter

    2016-02-01

    To investigate the effect of calcium ions on the disintegration of enteric-coated dosage forms, disintegration testing was performed on enteric-coated aspirin tablets in the presence and absence of calcium in the test media. The results show that the presence of calcium ions retards the disintegration of enteric-coated dosage forms. This finding, which has not been reported in scientific literature, sheds light on the importance of conducting well-designed detailed investigations into the potential of calcium from dietary sources, calcium supplements, antacids, and/or phosphate binders affecting the absorption of drugs formulated into enteric-coated dosage forms. Moreover, it shows the necessity to investigate the potential of the occurrence of additional nutrient-excipient interactions.

  3. Residues of DDT in brains and bodies of birds that died on dosage and in survivors

    USGS Publications Warehouse

    Stickel, L.F.; Stickel, W.H.; Christensen, R.

    1966-01-01

    Residues of 1,1 ,l-trichloro-2,2-bis(p-chlorophenyl)-ethane (DDT) and 1,1 -dichloro-2.2-bis(p-chlorophenyl)-ethane (DDD) in brains of cowbirds (Molothrus ater) killed hy dietary dosage of DDT were similar in birds that died after various lengths of time on dosage and in birds that died of delayed effects after as much as 40 days on clean food, Residues of DDT and DDD, but not of 1,1 -dichloro-2.2-bis-(p-chlorophenyl)-ethylene (DDE), were much lower in survivors 112 days after dosage. The relative importance of DDT and DDD in brains could nlot he determined, but DDE appeared not to be critical. Residues in brains of cowbirds were similar to those reported for robins, sparrows, eagles, and white rats. Residues in livers and carcass remainders (with the possible exception of DDD in the liver) appeared unsuitable for diagnosing the cause of death.

  4. Carte du Ciel, San Fernando zone

    NASA Astrophysics Data System (ADS)

    Abad, C.

    2014-06-01

    An updated summary of a future large astrometric catalogue is presented, based on the two most important astrometric projects carried out by the Real Instituto y Observatorio de la Armada de San Fernando (ROA). The goal is to make a catalogue of positions and proper motions based on ROA's Cart du Ciel (CdC) and the Astrographic Catalogue (AC) San Fernando zone plates, and the HAMC2 meridian circle catalogue. The CdC and AC plates are being reduced together to provide first-epoch positions while HAMC2 will provide second-epoch ones. New techniques have been applied, that range from using a commercial flatbed scanner to the proper reduction schemes to avoid systematics from it. Only thirty plates (out of 540) remain to be processed, due to scanning problems that are being solved.

  5. Le mouvement du pôle

    NASA Astrophysics Data System (ADS)

    Bizouard, Christian

    2012-03-01

    Les variations de la rotation terrestre. En conditionnant à la fois notre vie quotidienne, notre perception du ciel, et bon nombre de phénomènes géophysiques comme la formation des cyclones, la rotation de la Terre se trouve au croisement de plusieurs disciplines. Si le phenomena se faisait uniformément, le sujet serait vite discuté, mais c'est parce que la rotation terrestre varie, même imperceptiblement pour nos sens, dans sa vitesse angulaire comme dans la direction de son axe, qu'elle suscite un grand intérêt. D'abord pour des raisons pratiques : non seulement les aléas de la rotation terrestre modi_ent à la longue les pointés astrométriques à un instant donné de la journée mais in_uencent aussi les mesures opérées par les techniques spatiales ; en consequence l'exploitation de ces mesures, par exemple pour déterminer les orbites des satellites impliqués ou pratiquer le positionnement au sol, nécessite une connaissance précise de ces variations. Plus fondamentalement, elles traduisent les propriétés globales de la Terre comme les processus physiques qui s'y déroulent, si bien qu'en analysant les causes des fluctuations observées, on dispose d'un moyen de mieux connaître notre globe. La découverte progressive des fluctuations de la rotation de la Terre a une longue histoire. Sous l'angle des techniques d'observation, trois époques se pro-celle du pointé astrométrique à l'oeil nu, à l'aide d'instruments en bois ou métalliques (quart de cercle muraux par exemple). À partir du XVIIe siècle débute l'astrométrie télescopique dont les pointés sont complétés par des datations de plus en plus précises grâce à l'invention d'horloges régulées par balancier. Cette deuxième époque se termine vers 1960, avec l'avènement des techniques spatiales : les pointés astrométriques sont délaissés au profit de la mesure ultra-précise de durées ou de fréquences de signaux électromagnétiques, grâce à l'invention des horloges

  6. Measuring dosage: a key factor when assessing the relationship between prenatal case management and birth outcomes.

    PubMed

    Slaughter, Jaime C; Issel, L Michele; Handler, Arden S; Rosenberg, Deborah; Kane, Debra J; Stayner, Leslie T

    2013-10-01

    To assess whether a measure of prenatal case management (PCM) dosage is more sensitive than a dichotomous PCM exposure measure when evaluating the effect of PCM on low birthweight (LBW) and preterm birth (PTB). We constructed a retrospective cohort study (N = 16,657) of Iowa Medicaid-insured women who had a singleton live birth from October 2005 to December 2006; 28 % of women received PCM. A PCM dosage measure was created to capture duration of enrollment, total time with a case manager, and intervention breadth. Propensity score (PS)-adjusted odds ratios (ORs), and 95 % confidence intervals (95 % CIs) were calculated to assess the risk of each outcome by PCM dosage and the dichotomous PCM exposure measure. PS-adjusted ORs of PTB were 0.88 (95 % CI 0.70-1.11), 0.58 (95 % CI 0.47-0.72), and 1.43 (95 % CI 1.23-1.67) for high, medium, and low PCM dosage, respectively. For LBW, the PS-adjusted ORs were 0.76 (95 % CI 0.57-1.00), 0.64 (95 % CI 0.50-0.82), and 1.36 (95 % CI 1.14-1.63), for high, medium, and low PCM dosage, respectively. The PCM dichotomous participation measure was not significantly associated with LBW (OR = 0.95, 95 % CI 0.82-1.09) or PTB (0.97, 95 % CI 0.87-1.10). The reference group in each analysis is No PCM. PCM was associated with a reduced risk of adverse pregnancy outcomes for Medicaid-insured women in Iowa. PCM dosage appeared to be a more sensitive measure than the dichotomous measure of PCM participation.

  7. On the exfoliating polymeric cellular dosage forms for immediate drug release.

    PubMed

    Blaesi, Aron H; Saka, Nannaji

    2016-06-01

    The most prevalent pharmaceutical dosage forms at present-the oral immediate-release tablets and capsules-are granular solids. Though effective in releasing drug rapidly, development and manufacture of such dosage forms are fraught with difficulties inherent to particulate processing. Predictable dosage form manufacture could be achieved by liquid-based processing, but cast solid dosage forms are not suitable for immediate drug release due to their resistance to fluid percolation. To overcome this limitation, we have recently introduced cellular dosage forms that can be readily prepared from polymeric melts. It has been shown that open-cell structures comprising polyethylene glycol 8000 (PEG 8k) excipient and a drug exfoliate upon immersion in a dissolution medium. The drug is then released rapidly due to the large specific surface area of the exfoliations. In this work, we vary the molecular weight of the PEG excipient and investigate its effect on the drug release kinetics of structures with predominantly open-cell topology. We demonstrate that the exfoliation rate decreases substantially if the excipient molecular weight is increased from 12 to 100kg/mol, which causes the drug dissolution time to increase by more than a factor of ten. A model is then developed to elucidate the exfoliation behavior of cellular structures. Diverse transport processes are considered: percolation due to capillarity, diffusion of dissolution medium through the cell walls, and viscous flow of the saturated excipient. It is found that the lower exfoliation rate and the longer dissolution time of the dosage forms with higher excipient molecular weight are primarily due to the greater viscosity of the cell walls after fluid penetration.

  8. Classification moléculaire du cancer du sein au Maroc

    PubMed Central

    Fouad, Abbass; Yousra, Akasbi; Kaoutar, Znati; Omar, El Mesbahi; Afaf, Amarti; Sanae, Bennis

    2012-01-01

    Introduction La classification moléculaire des cancers du sein basée sur l'expression génique puis sur le profil protéique a permis de distinguer cinq groupes moléculaires: luminal A, luminal B, Her2/neu, basal-like et non-classées. L'objectif de cette étude réalisée au CHU Hassan II de Fès est de classer 335 cancers du sein infiltrant en groupes moléculaires, puis de les corréler avec les caractéristiques clinicopathologiques. Méthodes Etude rétrospective étalée sur 45 mois, comportant 335 patientes colligées au CHU pour le diagnostic et le suivi. Les tumeurs sont analysées histologiquement et classées après une étude immunohistochimique en groupes: luminal A, luminal B, Her2+, basal-like et non-classées. Résultats 54.3% des tumeurs sont du groupe luminal A, 16% luminal B, 11.3% Her2+, 11.3% basal-like et 7% non-classées. Le groupe luminal A renferme le plus faible taux de grade III, d'emboles vasculaires ainsi que de métastases; alors que le groupe des non-classées et basal-like représentent un taux élevé de grade III, une faible proportion d'emboles vasculaires et d'envahissement ganglionnaire. Ces facteurs sont significativement élevés dans les groupes luminal B et Her2+ avec un taux de survie globale de 78% et 76% respectivement. Dans le groupe luminal A, la survie globale des patientes est élevée (87%) alors qu'elle n'est que de 49% dans le groupe des triples négatifs (basal-like et non-classés). Conclusion Le groupe luminal B est différent du luminal A et il est de pronostic péjoratif vis à vis du groupe Her2+. Les caractéristiques clinicopathologiques concordent avec le profil moléculaire donc devraient être pris en considération comme facteurs pronostiques. PMID:23396646

  9. Impact socio professionnel de la libération chirurgicale du syndrome du canal carpien

    PubMed Central

    Kraiem, Aouatef Mahfoudh; Hnia, Hajer; Bouzgarrou, Lamia; Henchi, Mohamed Adnène; Khalfallah, Taoufik

    2016-01-01

    L’objectif de notre travail était d’étudier les conséquences socioprofessionnelles d’une libération chirurgicale du SCC. Il s’agit d’une étude transversale portant sur les sujets opérés pour un SCC d’origine professionnelle ; recensés dans le Service de Médecine de Travail et de Pathologies Professionnelles au CHU Tahar Sfar de Mahdia en Tunisie sur une période de 8 ans allant du 1 Janvier 2006 au mois Décembre 2013. Le recueil des données s’est basé sur une fiche d’enquête, portant sur la description des caractéristiques socioprofessionnelles, médicales, et sur le devenir professionnel des participants. Pour étudier les contraintes psychosociales au travail, nous avons adopté le questionnaire de Karasek. La durée d’arrêt de travail après libération chirurgicale du SCC était significativement liée à l’existence d’autres troubles musculo-squelettiques autre que le SCC, la déclaration du SCC en maladie professionnelle et à l’ancienneté professionnelle des salariés. Quant au devenir professionnel des salariés opérés, 50,7% ont gardé le même poste, 15,3% ont bénéficié d’un aménagement de poste et 33,8% ont bénéficié d’un changement de poste dans la même entreprise. Le devenir professionnel de ces salariés était corrélé à leurs qualifications professionnelles et au type de l’atteinte sensitive et/ou motrice du nerf médian à l’EMG. Un certain nombre de facteurs non lésionnels déterminaient la durée de l’arrêt de travail, alors que le devenir professionnel des opérés pour SCC dépendait essentiellement de leurs qualifications professionnelles et des données de l’électromyogramme. Il est certain que des travaux beaucoup plus larges permettraient d’affiner encore ces résultats. PMID:27800089

  10. Phase transformation considerations during process development and manufacture of solid oral dosage forms.

    PubMed

    Zhang, Geoff G Z; Law, Devalina; Schmitt, Eric A; Qiu, Yihong

    2004-02-23

    The quality and performance of a solid oral dosage form depends on the choice of the solid phase, the formulation design, and the manufacturing process. The potential for process-induced solid phase transformations must be evaluated during design and development of formulations and manufacturing processes. This article briefly reviews the basic principles of polymorphism, defines the classes of phase transformation and the underlying transformation mechanisms, and discusses respective kinetic factors. The potential phase transformations associated with common unit operations employed in manufacturing solid oral dosage forms are highlighted. Specific examples are given to illustrate the importance of solid phases, and process-induced phase transitions in formulation and process development.

  11. Effect of sex-sorted sperm dosage on conception rates in Holstein heifers and lactating cows.

    PubMed

    DeJarnette, J M; Nebel, R L; Marshall, C E; Moreno, J F; McCleary, C R; Lenz, R W

    2008-05-01

    Ejaculates were collected by artificial vagina from 3 Holstein sires and sorted to 90% purity for X-chromosome-bearing spermatozoa (range 88 to 93%) using flow cytometry. Sorted sperm were diluted to 2.1, 3.5, or 5.0 x 10(6) sperm per dose in an egg yolk (20%), Tris, glycerol (7%) extender. Collections were repeated until >600 straws per sperm dose per sire were obtained. Each sperm dose was loaded into color-coded 0.25-mL French straws, with alternate colors used to define treatments across sires. Within sires, straws were packaged at 9 per cane (3 of each color) and strategically allocated to 75 Holstein herds with targets for 50% use in heifers and 50% in lactating cows. Straw color was recorded in the on-farm record-keeping system at the time of insemination. Data were analyzed separately for cows and heifers. Among heifers, a total of 2,125 usable records were retrieved from 51 herds (238 +/- 5.5 services/ sperm dose per sire, range: 218 to 263). Conception rates in heifers were influenced by the sire x sperm dosage interaction. Within sire A, conception rates of heifers were greater for the 5 x 10(6) (59.5%) than for the 2.1 x 10(6) (46.4%) sperm dose and intermediate for the 3.5 x 10(6) sperm dose (52.2%). However, across sires, sperm dosage had no effect on heifer conception rates (46.7, 51.2, and 52.5% for the 2.1, 3.5, and 5.0 x 10(6) sperm dosages, respectively). Among cows, a total of 2,369 services were retrieved from 56 herds (263 +/- 8.8 services/sperm dose per sire, range: 233 to 303). Conception rates of cows (29.4%) were not affected by sire or sperm dosage (27.0, 29.1, and 30.3% for the 2.1, 3.5, and 5.0 x 10(6) sperm dosages, respectively). In conclusion, these data indicate that an increased sperm dosage may enhance virgin heifer conception rates for some (but not all) sires, whereas neither sire nor sexed-sperm dosage affected conception rates of lactating cows. Additional studies of sexed-sperm dosage across a larger sampling of bulls are

  12. Intrapelvic prosthesis to prevent injury of the small intestine with high dosage pelvic irradiation

    SciTech Connect

    Sugarbaker, P.H.

    1983-09-01

    The major complication to delivering tumoricidal dosages of radiation to the pelvis is radiation damage to the loops of the small intestine located within the radiation field. To exclude the small intestine from the pelvis after extensive pelvic surgical treatment, prosthetic materials are used. A transabdominal baffle made of prosthetic mesh separates pelvic and abdominal cavities. A Silastic implant, usually used in the reconstruction of the breast, is used in the pelvis to occupy space. In so doing, all of the small intestine can be excluded from the pelvic cavity and dosages of radiation to 6,500 rads can be administered.

  13. Biowaiver monographs for immediate release solid oral dosage forms: ranitidine hydrochloride.

    PubMed

    Kortejärvi, H; Yliperttula, M; Dressman, J B; Junginger, H E; Midha, K K; Shah, V P; Barends, D M

    2005-08-01

    Literature and experimental data relevant to the decision to allow a waiver of in vivo bioequivalence testing for the approval of immediate release (IR) solid oral dosage forms containing ranitidine hydrochloride are reviewed. According to the current Biopharmaceutics Classification System (BCS), ranitidine hydrochloride should be assigned to Class III. However, based on its therapeutic and therapeutic index, pharmacokinetic properties and data related to the possibility of excipient interactions, a biowaiver can be recommended for IR solid oral dosage forms that are rapidly dissolving and contain only those excipients as reported in this study.

  14. Analysis of molecular interactions in solid dosage forms; challenge to molecular pharmaceutics.

    PubMed

    Yamamoto, Keiji; Limwikrant, Waree; Moribe, Kunikazu

    2011-01-01

    The molecular states of active pharmaceutical ingredients (APIs) in pharmaceutical dosage forms strongly affect the properties and quality of a drug. Various important fundamental physicochemical studies were reviewed from the standpoint of molecular pharmaceutics. Mechanochemical effects were evaluated in mixtures of APIs and pharmaceutical additives. Amorphization, complex formation and nanoparticle formation are observed after grinding process depending on the combination of APIs and pharmaceutical additives. Sealed-heating method and mesoporous materials have been used to investigate drug molecular interactions in dosage forms. Molecular states have been investigated using powder X-ray diffraction, thermal analysis, IR, solid state fluorometry, and NMR.

  15. Genome-Wide Dosage-Dependent and -Independent Regulation Contributes to Gene Expression and Evolutionary Novelty in Plant Polyploids.

    PubMed

    Shi, Xiaoli; Zhang, Changqing; Ko, Dae Kwan; Chen, Z Jeffrey

    2015-09-01

    Polyploidy provides evolutionary and morphological novelties in many plants and some animals. However, the role of genome dosage and composition in gene expression changes remains poorly understood. Here, we generated a series of resynthesized Arabidopsis tetraploids that contain 0-4 copies of Arabidopsis thaliana and Arabidopsis arenosa genomes and investigated ploidy and hybridity effects on gene expression. Allelic expression can be defined as dosage dependent (expression levels correlate with genome dosages) or otherwise as dosage independent. Here, we show that many dosage-dependent genes contribute to cell cycle, photosynthesis, and metabolism, whereas dosage-independent genes are enriched in biotic and abiotic stress responses. Interestingly, dosage-dependent genes tend to be preserved in ancient biochemical pathways present in both plant and nonplant species, whereas many dosage-independent genes belong to plant-specific pathways. This is confirmed by an independent analysis using Arabidopsis phylostratigraphic map. For A. thaliana loci, the dosage-dependent alleles are devoid of TEs and tend to correlate with H3K9ac, H3K4me3, and CG methylation, whereas the majority of dosage-independent alleles are enriched with TEs and correspond to H3K27me1, H3K27me3, and CHG (H = A, T, or C) methylation. Furthermore, there is a parent-of-origin effect on nonadditively expressed genes in the reciprocal allotetraploids especially when A. arenosa is used as the pollen donor, leading to metabolic and morphological changes. Thus, ploidy, epigenetic modifications, and cytoplasmic-nuclear interactions shape gene expression diversity in polyploids. Dosage-dependent expression can maintain growth and developmental stability, whereas dosage-independent expression can facilitate functional divergence between homeologs (subfunctionalization and/or neofunctionalization) during polyploid evolution.

  16. The Cri-Du-Chat Syndrome: A Case Study.

    ERIC Educational Resources Information Center

    Sykes, Stewart C.; Christie, Margarette A.

    1987-01-01

    The developmental history of a 14-year-old girl with Cri-Du-Chat Syndrome (a genetic disorder characterized by a distinctive cry and severe physical and intellectual disabilities) is reported. (Author/DB)

  17. Genetics Home Reference: cri-du-chat syndrome

    MedlinePlus

    ... syndrome March of Dimes: Chromosomal Conditions Merck Manual Consumer Version: Overview of Chromosomal Abnormalities Orphanet: Monosomy 5p ... Pinkel D. High-resolution mapping of genotype-phenotype relationships in cri du chat syndrome using array comparative ...

  18. 1. Historic American Buildings Survey, drawn by Pierre du Simitiere ...

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

    1. Historic American Buildings Survey, drawn by Pierre du Simitiere (papers in Philadelphia Library) DRAWING OF REDWOOD LIBRARY IN 1768. - Redwood Library, 50 Bellevue Avenue, Newport, Newport County, RI

  19. Atmosphere Assisted Machining of Depleted Uranium (DU) Penetrators

    DTIC Science & Technology

    1987-05-01

    tooling should be approximately $75,000 each. Lessons learned in the Vacuum Induction Remelt MM&T and the chip melts made on this program point out the...AD-E-401 528 Cutwator Report ARCCD-CR-6600S (V) ATMOSPHERE ASSISTED MACMINING DEPLETED URANIUM (DU) PENETRATORS DTic Charles E. Lathe"rOwn ELECTE...E-401 528 Contractor Report ARCCD-CR-86008 ATMOSPHERE ASSISTED MACHINING OF DEPLETED URANIUM (DU) PENETRATORS Charles E. Latham-Brown Frank Porter

  20. Peters anomaly in cri-du-chat syndrome.

    PubMed

    Hope, William C; Cordovez, Jose A; Capasso, Jenina E; Hammersmith, Kristin M; Eagle, Ralph C; Lall-Trail, Joel; Levin, Alex V

    2015-06-01

    The cri-du-chat syndrome is a rare genetic disorder caused by deletions in the short arm of chromosome 5. It presents with a distinctive catlike high-pitched cry, psychomotor delays, microcephaly, craniofacial abnormalities, and, in many cases, ocular findings. We report the first child with cri-du-chat and the findings of unilateral corneal staphyloma due to Peters anomaly and retinal dysplasia.

  1. Anaesthetic considerations for the patient with cri du chat syndrome.

    PubMed

    Brislin, R P; Stayer, S A; Schwartz, R E

    1995-01-01

    Cri du chat syndrome is an inherited disease affecting multiple organ systems. Most characteristic is the anatomical abnormality of the larynx resulting in a cat-like cry. Issues important in developing an anaesthetic plan include: anatomical abnormalities of the airway, congenital heart disease, hypotonia, mental retardation, and temperature maintenance. We report the case of a 33-month-old patient with cri du chat syndrome undergoing patent ductus arteriosus (PDA) ligation and discuss the anaesthetic issues.

  2. Determination of periodontopathogens in patients with Cri du chat syndrome

    PubMed Central

    Ballesta-Mudarra, Sofía; Torres-Lagares, Daniel; Rodríguez-Caballero, Ángela; Yáñez-Vico, Rosa M.; Solano-Reina, Enrique; Perea-Pérez, Evelio

    2013-01-01

    Objectives: Cri du chat syndrome is a genetic alteration associated with some oral pathologies. However, it has not been described previously any clinical relationship between the periodontal disease and the syndrome. The purpose of this comparative study was to compare periodontopathogenic flora in a group with Cri du chat syndrome and another without the síndrome, to assess a potential microbiological predisposition to suffer a periodontitis. Study Design: The study compared nineteen subjects with Cri du chat Syndrome with a control group of nineteen patients without it. All patients were clinically evaluated by periodontal probing, valuing the pocket depth, the clinical attachmente level and bleeding on probing. There were no significant differences between both groups. Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Prevotella intermedia, Tannerella forsythia and Treponema denticola were detected by multiplex-PCR using 16S rDNA (microIDENT). Results: When A. actinomycetemcomitans, P. gingivalis, P. intermedia and T. denticola were compared, no statistically significant differences were found between the two groups (p>0.05). The value of T. forsythia was significantly higher for Cri du chat syndrome (31.6%) than for the control group (5.3%). The odds ratio for T. forsythia was 8.3. Conclusions: In the present study T. forsythia is associated with Cri du chat syndrome subjects and not with healthy subjects. Key words:Cri du Chat syndrome, periodontal health, microbiology, special care dentistry. PMID:24121919

  3. Oxidation states of uranium in DU particles from Kosovo.

    PubMed

    Salbu, B; Janssens, K; Lind, O C; Proost, K; Danesi, P R

    2003-01-01

    The oxidation states of uranium contained in depleted uranium (DU) particles were determined by synchrotron radiation based micro-XANES, applied to individual particles in soil samples collected at Ceja Mountain, Kosovo. Based on scanning electron microscopy (SEM) with XRMA prior to micro-XANES, DU particles ranging from submicrons to about 30 microm (average size: 2 microm or less) were identified. Compared to well-defined standards, all investigated DU particles were oxidized. About 50% of the DU particles were characterized as UO2, the remaining DU particles present were U3O8 or a mixture of oxidized forms (ca. 2/3 UO2, 1/3 U3O8). Since the particle weathering rate is expected to be higher for U3O8 than for UO2, the presence of respiratory U3O8 and UO2 particles, their corresponding weathering rates and subsequent remobilisation of U from DU particles should be included in the environmental or health impact assessments.

  4. Effets du titane et du niobium sur l'oxydation à 950circC d'aciers ferritiques

    NASA Astrophysics Data System (ADS)

    Issartel, C.; Buscail, H.; Caudron, E.; Cueff, R.; Riffard, F.; El Messki, S.; Karimi, N.; Antoni, L.

    2004-11-01

    Nous avons étudié l'effet du titane et du niobium sur l'oxydation à 950circC d'un acier Fe-Cr chrominoformeur. La DRX in situ montre que le titane semble s'oxyder en formant Cr{2}TiO{5} et TiO{2} qui contribuent à une augmentation de la prise de masse des échantillons. Une partie du titane issu de ces oxydes semble doper la couche de chromine. Sa présence augmente la concentration en lacunes cationiques dans la chromine et augmente donc la diffusion du chrome dans la couche. Nous avons aussi montré que le niobium n'a pas d'influence sur l'oxydation de ce type d'acier à 950circC.

  5. Tumeur du sac vitellin du testicule au stade IIIc métastatique : à propos d’un cas

    PubMed Central

    Zizi, Mohamed; Ziouziou, Imad; El Yacoubi, Souhail; Khmou, Mouna; Jahid, Ahmed; Mahassini, Najat; Karmouni, Tariq; El Khader, Khalid; Koutani, Abdellatif; Andaloussi, Ahmed Iben Attya

    2014-01-01

    Résumé Les tumeurs du sac vitellin du testicule sont rares chez l’adulte. Ces tumeurs se caractérisent par un mauvais pronostic à un stade métastatique avancé. Cependant, nous rapportons, dans le présent article, le cas clinique d’un adulte de 32 ans qui présentait une tumeur du sac vitellin du testicule au stade IIIc métastatique. Ce patient a subi une orchidectomie haute, accompagnée de quatre cycles de chimiothérapie à base de bléomycine, d’étoposide et de cisplatine. Il a répondu complètement au traitement, moyennant un recul de deux ans. PMID:25295144

  6. Prise en charge du cancer du col utérin durant la grossesse: à propos de 05 cas

    PubMed Central

    El Mazghi, Abderrahman; Bouhafa, Touria; Loukili, Kaoutar; El Kacemi, Hanan; Lalya, Issam; Hassouni, Khalid

    2014-01-01

    L'association d'un cancer du col utérin avec une grossesse est une éventualité rare. Son incidence est assez mal évaluée, elle se situe selon les études entre 1 et 2/10 000. Lorsque la découverte en est faite, il faut conjuguer deux impératifs parfois totalement divergents: le traitement de la mère et la prise en charge du foetus. Cette association pose schématiquement quatre grands problèmes, qui sont: Celui du diagnostic, qui est loin d’être évident, compte tenu des remaniements cervicaux observés en début de gestation, le pronostic de l'affection, la date du traitement chirurgical et du délai entre le diagnostic et la prise en charge thérapeutique, enfin et de manière plus accessoire, le devenir de la grossesse et le mode d'accouchement. Nous rapportons une série de 5 cas de cancer du col utérin découverts au cours de la grossesse colligés dans notre service entre 2010 et 2013. La prise en charge thérapeutique est identique à celle des patientes en dehors de la grossesse même si quelques adaptations sont nécessaires du fait de l’état gravide, le pronostic du cancer ne semble pas être modifié par la grossesse. PMID:25852788

  7. A nondestructive technique to determine the rate of oxygen permeation into solid dosage forms.

    PubMed

    Felton, L A; Timmins, G S

    2006-02-01

    The current study investigated the use of electron paramagnetic resonance (EPR) spectroscopy as a nondestructive method to quantify the partial pressure of oxygen (PO2) in tablets and hard shell capsules. Lithium phthalocyanine crystals (LiPC) were placed inside the dosage forms. The peak-to-peak linewidth of the first derivative of the LiPC EPR spectra was measured and, by calibration tables, the oxygen partial pressure, pO2, within the dosage form was determined. The intra-dosage form pO2 was followed as a function of time after changing the exterior gas stream composition. Results showed initial oxygen concentrations comparable to atmospheric levels in all tablets and capsules investigated. Oxygen rapidly permeated into unsealed gelatin and cellulosic hard shell capsules. Banding at the cap/body joint significantly reduced the oxygen permeation rate. Oxygen also rapidly permeated into tablet compacts, regardless of the compressional force used during tableting, while application of a polymeric film significantly decreased the rate of oxygen permeation. This EPR technique was shown to be a suitable nondestructive method to study oxygen permeation kinetics in solid dosage forms.

  8. Dynamic Modulation of Innate Immune Response by Varying Dosages of Lipopolysaccharide (LPS) in Human Monocytic Cells*

    PubMed Central

    Morris, Matthew C.; Gilliam, Elizabeth A.; Button, Julia; Li, Liwu

    2014-01-01

    Innate monocytes and macrophages can be dynamically programmed into distinct states depending upon the strength of external stimuli. Innate programming may bear significant relevance to the pathogenesis and resolution of human inflammatory diseases. However, systems analyses with regard to the dynamic programming of innate leukocytes are lacking. In this study, we focused on the dynamic responses of human promonocytic THP-1 cells to lipopolysaccharide (LPS). We observed that varying dosages of LPS differentially modulate the expression of selected pro- and anti- inflammatory mediators such as IL-6 and IL-33. Super-low dosages of LPS preferentially induced the pro-inflammatory mediator IL-6, while higher dosages of LPS induced both IL-6 and IL-33. Mechanistically, we demonstrated that super-low and high doses of LPS cause differential activation of GSK3 and Akt, as well as the transcription factors FoxO1 and CREB. Inhibition of GSK3 enabled THP-1 cells to express IL-33 when challenged with super-low dose LPS. On the other hand, activation of CREB with adenosine suppressed IL-6 expression. Taken together, our study reveals a dynamic modulation of monocytic cells in response to varying dosages of endotoxin, and may shed light on our understanding of the dynamic balance that controls pathogenesis and resolution of inflammatory diseases. PMID:24970893

  9. Use of Problem Based Discussion Sessions in a First Year Pharmaceutical Dosage Forms Course.

    ERIC Educational Resources Information Center

    Brazeau, Gayle A.; Hughes, Jeffrey A.; Prokai, Laszlo

    1999-01-01

    A study investigated the effectiveness of incorporating discussion groups and problem solving in a first-year pharmaceutical dosage-forms course. Students responded positively to the group discussions focusing on problem solving and the discussion summaries, which demonstrated the diversity of approaches to problem solving and focused their…

  10. 76 FR 72619 - Ophthalmic and Topical Dosage Form New Animal Drugs; Eprinomectin

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-25

    ... HUMAN SERVICES Food and Drug Administration 21 CFR Part 524 Ophthalmic and Topical Dosage Form New Animal Drugs; Eprinomectin AGENCY: Food and Drug Administration, HHS. ACTION: Final rule; technical amendment. SUMMARY: The Food and Drug Administration (FDA) is amending the animal drug regulations...

  11. 78 FR 42006 - Oral Dosage Form New Animal Drugs; Nicarbazin; Oclacitinib; Zilpaterol

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-15

    ... HUMAN SERVICES Food and Drug Administration 21 CFR Parts 520 and 558 Oral Dosage Form New Animal Drugs; Nicarbazin; Oclacitinib; Zilpaterol AGENCY: Food and Drug Administration, HHS. ACTION: Final rule. SUMMARY: The Food and Drug Administration (FDA) is amending the animal drug regulations to reflect...

  12. Orally disintegrating films and mini-tablets-innovative dosage forms of choice for pediatric use.

    PubMed

    Preis, Maren

    2015-04-01

    Oral drug delivery is a non-invasive and therefore a very convenient route of administration. Orally disintegrating dosage forms, like soluble films and (mini-)tablets, appear promising for use in the pediatric population. New guidance for the development of pediatric medicines has been published, which provides considerations on how pediatric products should be designed. However, most of the considerations leave a lot of room for interpretations. Bearing in mind the different aspects discussed in the latest guideline, the use of orally disintegrating films and tablets, in particular, small-sized tablets, is discussed and reflected upon by providing evidence from the scientific literature. The available dosage forms for children are various and examples of currently licensed products for use in the pediatric population were compiled. Aspects such as the appropriateness for pediatrics, the choice of excipients, the opportunities for modified drug release preparations or fixed-dose combinations, the acceptability and palatability, and also limitations were discussed with respect to the new dosage forms of orally disintegrating films and mini-tablets. This paper points out that innovation in pediatric medicines are planned and should be encouraged; however, supported by the regulatory guidance, only general considerations are provided. Nevertheless, the guideline summarizes multiple points to consider during the development of medicines for pediatric use. Considering the scientific evidence and the regulatory guidance, orally disintegrating dosage forms, like soluble films and (mini-)tablets, offer an innovative solution for pediatric drug delivery.

  13. Benzofuran ketone dosage-dependent rayless goldenrod (Isocoma pluriflora) toxicosis in a caprine model

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The objectives of this study were to determine the dosage of benzofuran ketone compounds (tremetone, 3-hydroxytremetone, dehydrotremetone, and 3-oxyangeloyltremetone) and the duration of exposure to these compounds required to produce clinical signs and the associated pathological changes of rayles ...

  14. The Effects of Methylphenidate in the Classroom: What Dosage, for Which Children, for What Problems?

    ERIC Educational Resources Information Center

    Northup, John; Gulley, Veronica; Edwards, Stephanie; Fountain, Laura

    2001-01-01

    In this study we conducted single-case analyses of the dosage and time-course effects of methylphenidate (MPH; Ritalin) on disruptive classroom behavior, math and reading performance, and social engagement. Clear individual differences were demonstrated (a) across children; (b) across academic, behavioral, and social domains of functioning; (c)…

  15. The Effects of Methylphenidate in the Classroom: What Dosage, for Which Children, for What Problems?

    ERIC Educational Resources Information Center

    Northup, John; Gulley, Veronica; Edwards, Stephanie; Fountain, Laura

    2001-01-01

    Single-case analyses were conducted of the dosage and time-course effects of methylphenidate on disruptive classroom behavior, math and reading performance, and social engagement. In contrast to previous studies, clear individual differences were demonstrated: across children; across academic, behavioral, and social domains of functioning; for…

  16. Purifying Selection Maintains Dosage-Sensitive Genes during Degeneration of the Threespine Stickleback Y Chromosome

    PubMed Central

    White, Michael A.; Kitano, Jun; Peichel, Catherine L.

    2015-01-01

    Sex chromosomes are subject to unique evolutionary forces that cause suppression of recombination, leading to sequence degeneration and the formation of heteromorphic chromosome pairs (i.e., XY or ZW). Although progress has been made in characterizing the outcomes of these evolutionary processes on vertebrate sex chromosomes, it is still unclear how recombination suppression and sequence divergence typically occur and how gene dosage imbalances are resolved in the heterogametic sex. The threespine stickleback fish (Gasterosteus aculeatus) is a powerful model system to explore vertebrate sex chromosome evolution, as it possesses an XY sex chromosome pair at relatively early stages of differentiation. Using a combination of whole-genome and transcriptome sequencing, we characterized sequence evolution and gene expression across the sex chromosomes. We uncovered two distinct evolutionary strata that correspond with known structural rearrangements on the Y chromosome. In the oldest stratum, only a handful of genes remain, and these genes are under strong purifying selection. By comparing sex-linked gene expression with expression of autosomal orthologs in an outgroup, we show that dosage compensation has not evolved in threespine sticklebacks through upregulation of the X chromosome in males. Instead, in the oldest stratum, the genes that still possess a Y chromosome allele are enriched for genes predicted to be dosage sensitive in mammals and yeast. Our results suggest that dosage imbalances may have been avoided at haploinsufficient genes by retaining function of the Y chromosome allele through strong purifying selection. PMID:25818858

  17. 78 FR 57057 - Oral Dosage Form New Animal Drugs; Amprolium; Meloxicam

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-09-17

    ... HUMAN SERVICES Food and Drug Administration 21 CFR Part 520 Oral Dosage Form New Animal Drugs; Amprolium....100 Yes....... CE \\1\\. Health Corp., (amprolium) 9.6% as a generic GlenPointe Oral Solution. copy of........... Ceva Sante MELOXIDYL Original approval 520.1350 Yes....... CE \\1\\. Animale, 10 (meloxicam) Oral as...

  18. 21 CFR 200.7 - Supplying pharmacists with indications and dosage information.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 4 2010-04-01 2010-04-01 false Supplying pharmacists with indications and dosage... SERVICES (CONTINUED) DRUGS: GENERAL GENERAL General Provisions § 200.7 Supplying pharmacists with... Cosmetic Act that prevent a manufacturer of prescription drugs from sending the pharmacist data he needs...

  19. Accelerated in vitro release testing methods for extended release parenteral dosage forms

    PubMed Central

    Shen, Jie; Burgess, Diane J.

    2012-01-01

    Objectives This review highlights current methods and strategies for accelerated in vitro drug release testing of extended release parenteral dosage forms such as polymeric microparticulate systems, lipid microparticulate systems, in situ depot-forming systems, and implants. Key findings Extended release parenteral dosage forms are typically designed to maintain the effective drug concentration over periods of weeks, months or even years. Consequently, “real-time” in vitro release tests for these dosage forms are often run over a long time period. Accelerated in vitro release methods can provide rapid evaluation and therefore are desirable for quality control purposes. To this end, different accelerated in vitro release methods using United States Pharmacopoeia (USP) apparatus have been developed. Different mechanisms of accelerating drug release from extended release parenteral dosage forms, along with the accelerated in vitro release testing methods currently employed are discussed. Conclusions Accelerated in vitro release testing methods with good discriminatory ability are critical for quality control of extended release parenteral products. Methods that can be used in the development of in vitro-in vivo correlation (IVIVC) are desirable, however for complex parenteral products this may not always be achievable. PMID:22686344

  20. 77 FR 4226 - Oral Dosage Form New Animal Drugs; Gentamicin Sulfate

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-27

    ... HUMAN SERVICES Food and Drug Administration 21 CFR Part 520 Oral Dosage Form New Animal Drugs... Administration (FDA) is amending the animal drug regulations to reflect approval of an original abbreviated new animal drug application (ANADA) filed by Cross Vetpharm Group, Ltd. The ANADA provides for use...

  1. 76 FR 40229 - Oral Dosage Form New Animal Drugs; Change of Sponsor

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-08

    ... HUMAN SERVICES Food and Drug Administration 21 CFR Part 520 Oral Dosage Form New Animal Drugs; Change of... Administration (FDA) is amending the animal drug regulations to reflect a change of sponsor for a new animal drug.... 801-808. List of Subjects in 21 CFR Part 520 Animal drugs. Therefore, under the Federal Food,...

  2. Female mice lacking Xist RNA show partial dosage compensation and survive to term

    PubMed Central

    Yang, Lin; Kirby, James E.; Sunwoo, Hongjae; Lee, Jeannie T.

    2016-01-01

    X-chromosome inactivation (XCI) compensates for differences in X-chromosome number between male and female mammals. XCI is orchestrated by Xist RNA, whose expression in early development leads to transcriptional silencing of one X chromosome in the female. Knockout studies have established a requirement for Xist with inviability of female embryos that inherit an Xist deletion from the father. Here, we report that female mice lacking Xist RNA can, surprisingly, develop and survive to term. Xist-null females are born at lower frequency and are smaller at birth, but organogenesis is mostly normal. Transcriptomic analysis indicates significant overexpression of hundreds of X-linked genes across multiple tissues. Therefore, Xist-null mice can develop to term in spite of a deficiency of dosage compensation. However, the degree of X-autosomal dosage imbalance was less than anticipated (1.14-fold to 1.36-fold). Thus, partial dosage compensation can be achieved without Xist, supporting the idea of inherent genome balance. Nevertheless, to date, none of the mutant mice has survived beyond weaning stage. Sudden death is associated with failure of postnatal organ maturation. Our data suggest Xist-independent mechanisms of dosage compensation and demonstrate that small deviations from X-autosomal balance can have profound effects on overall fitness. PMID:27542829

  3. The origin and evolution of vertebrate sex chromosomes and dosage compensation

    PubMed Central

    Livernois, A M; Graves, J A M; Waters, P D

    2012-01-01

    In mammals, birds, snakes and many lizards and fish, sex is determined genetically (either male XY heterogamy or female ZW heterogamy), whereas in alligators, and in many reptiles and turtles, the temperature at which eggs are incubated determines sex. Evidently, different sex-determining systems (and sex chromosome pairs) have evolved independently in different vertebrate lineages. Homology shared by Xs and Ys (and Zs and Ws) within species demonstrates that differentiated sex chromosomes were once homologous, and that the sex-specific non-recombining Y (or W) was progressively degraded. Consequently, genes are left in single copy in the heterogametic sex, which results in an imbalance of the dosage of genes on the sex chromosomes between the sexes, and also relative to the autosomes. Dosage compensation has evolved in diverse species to compensate for these dose differences, with the stringency of compensation apparently differing greatly between lineages, perhaps reflecting the concentration of genes on the original autosome pair that required dosage compensation. We discuss the organization and evolution of amniote sex chromosomes, and hypothesize that dosage insensitivity might predispose an autosome to evolving function as a sex chromosome. PMID:22086077

  4. 76 FR 49649 - Oral Dosage Form New Animal Drugs; Change of Sponsor; Chlortetracycline; Sulfamethazine

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-11

    ... / Thursday, August 11, 2011 / Rules and Regulations#0;#0; ] DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Part 520 Oral Dosage Form New Animal Drugs; Change of Sponsor... for five new animal drug applications (NADAs) from Fort Dodge Animal Health, Division of...

  5. 77 FR 28252 - Oral Dosage Form New Animal Drugs; Change of Sponsor; Griseofulvin Powder; Levamisole...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-14

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Part 520 Oral Dosage Form New Animal Drugs; Change of... hydrochloride soluble powder from Teva Animal Health, Inc., to Cross Vetpharm Group, Ltd. DATES: This rule...

  6. Controlled study in diabetic children comparing insulin-dosage adjustment by manual and computer algorithms.

    PubMed

    Chiarelli, F; Tumini, S; Morgese, G; Albisser, A M

    1990-10-01

    A controlled trial of a new microprocessor device for insulin-dosage adjustment was undertaken in two matched groups of a priori well-controlled diabetic children. A prospective study design with three equal 8-wk periods was used. In the first period, both groups used manual methods for insulin-dosage adjustment after manual criteria. In the second period, one group of children adjusted insulin dosage by computer algorithms, whereas the other continued to use manual methods. In the third period, both groups again adjusted insulin by traditional methods. Mean premeal glycemia and glycosylated hemoglobin levels did not change in either group throughout the study. During the second period, episodes of hypoglycemia were more frequent in children without the computer than in those who used the device. In keeping with the latter outcome, the group that used the microprocessor device was given less insulin in the second period than the first (0.88 +/- 0.02 vs. 0.94 +/- 0.02 U.kg-1.day-1, P less than 0.0001) and in comparison to the control group of patients who concurrently were given an increased insulin dose in the second period compared with the first. This study showed that insulin treatment through specific computer-mediated dosage-adjusting algorithms was safe and minimized hypoglycemia by effectively accommodating seasonally changing insulin requirements. We recommend the device to help diabetic children and their families in the care of insulin-dependent diabetes.

  7. Biorelevant in vitro performance testing of orally administered dosage forms-workshop report.

    PubMed

    Reppas, Christos; Friedel, Horst-Dieter; Barker, Amy R; Buhse, Lucinda F; Cecil, Todd L; Keitel, Susanne; Kraemer, Johannes; Morris, J Michael; Shah, Vinod P; Stickelmeyer, Mary P; Yomota, Chikako; Brown, Cynthia K

    2014-07-01

    Biorelevant in vitro performance testing of orally administered dosage forms has become an important tool for the assessment of drug product in vivo behavior. An in vitro performance test which mimics the intraluminal performance of an oral dosage form is termed biorelevant. Biorelevant tests have been utilized to decrease the number of in vivo studies required during the drug development process and to mitigate the risk related to in vivo bioequivalence studies. This report reviews the ability of current in vitro performance tests to predict in vivo performance and generate successful in vitro and in vivo correlations for oral dosage forms. It also summarizes efforts to improve the predictability of biorelevant tests. The report is based on the presentations at the 2013 workshop, Biorelevant In Vitro Performance Testing of Orally Administered Dosage Forms, in Washington, DC, sponsored by the FIP Dissolution/Drug Release Focus Group in partnership with the American Association of Pharmaceutical Scientists (AAPS) and a symposium at the AAPS 2012 Annual meeting on the same topic.

  8. Biowaiver monograph for immediate-release solid oral dosage forms: fluconazole.

    PubMed

    Charoo, Naseem; Cristofoletti, Rodrigo; Graham, Alexandra; Lartey, Paul; Abrahamsson, Bertil; Groot, D W; Kopp, Sabine; Langguth, Peter; Polli, James; Shah, Vinod P; Dressman, Jennifer

    2014-12-01

    Literature data pertaining to the decision to allow a waiver of in vivo bioequivalence (BE) testing requirements for the approval of immediate release (IR) solid oral dosage forms containing fluconazole as the only active pharmaceutical ingredient (API) are reviewed. The decision is based on solubility, dissolution, permeability, therapeutic index, pharmacokinetic parameters, pharmacodynamic properties, and other relevant data. BE/bioavailability (BA) problems and drug-excipients interaction data were also reviewed and taken into consideration. According to the biopharmaceutics classification system (BCS), fluconazole in polymorphic forms II and III is a BCS class I drug and has a wide therapeutic index. BE of test formulations from many different manufacturers containing different excipients confirmed that the risk of bioinequivalence because of formulation and manufacturing factors is low. It was inferred that risk can be further reduced if in vitro studies are performed according to biowaiver guidelines. Thus, it is concluded that a biowaiver can be recommended for fluconazole IR dosage forms if (a) fluconazole is present as polymorphic form II or III or any other form/mixture showing high solubility, (b) the selection of excipients be limited to those found in IR drug products approved in International Conference on Harmonisation (ICH) countries for the same dosage form and used in their usual amounts, and (c) both the test and comparator dosage form are very rapidly dissolving, or, rapidly dissolving throughout the shelf life with similar dissolution profiles at pH 1.2, 4.5, and 6.8.

  9. Caenorhabditis elegans Dosage Compensation Regulates Histone H4 Chromatin State on X Chromosomes

    PubMed Central

    Wells, Michael B.; Snyder, Martha J.; Custer, Laura M.

    2012-01-01

    Dosage compensation equalizes X-linked gene expression between the sexes. This process is achieved in Caenorhabditis elegans by hermaphrodite-specific, dosage compensation complex (DCC)-mediated, 2-fold X chromosome downregulation. How the DCC downregulates gene expression is not known. By analyzing the distribution of histone modifications in nuclei using quantitative fluorescence microscopy, we found that H4K16 acetylation (H4K16ac) is underrepresented and H4K20 monomethylation (H4K20me1) is enriched on hermaphrodite X chromosomes in a DCC-dependent manner. Depletion of H4K16ac also requires the conserved histone deacetylase SIR-2.1, while enrichment of H4K20me1 requires the activities of the histone methyltransferases SET-1 and SET-4. Our data suggest that the mechanism of dosage compensation in C. elegans involves redistribution of chromatin-modifying activities, leading to a depletion of H4K16ac and an enrichment of H4K20me1 on the X chromosomes. These results support conserved roles for histone H4 chromatin modification in worm dosage compensation analogous to those seen in flies, using similar elements and opposing strategies to achieve differential 2-fold changes in X-linked gene expression. PMID:22393255

  10. 75 FR 54018 - Implantation or Injectable Dosage Form New Animal Drugs; Florfenicol and Flunixin

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-03

    ... Administration 21 CFR Part 522 [Docket No. FDA-2010-N-0002] Implantation or Injectable Dosage Form New Animal... Mycoplasma bovis to the bovine respiratory disease (BRD) pathogens for which use of an injectable solution... flunixin meglumine), a combination drug injectable solution. The supplement adds M. bovis to the...

  11. 76 FR 27888 - Implantation or Injectable Dosage Form New Animal Drugs; Gonadotropin Releasing Factor-Diphtheria...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-13

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Part 522 Implantation or Injectable Dosage Form New... for Veterinary Medicine, 21 CFR part 522 is amended as follows: PART 522--IMPLANTATION OR...

  12. 75 FR 13225 - Implantation or Injectable Dosage Form New Animal Drugs; Flunixin

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-19

    ... HUMAN SERVICES Food and Drug Administration 21 CFR Part 522 Implantation or Injectable Dosage Form New... provides for the use of flunixin meglumine injectable solution in swine. DATES: This rule is effective...) Injectable Solution in swine for control of pyrexia associated with swine respiratory disease. Cross...

  13. Distinct contributions of MSL complex subunits to the transcriptional enhancement responsible for dosage compensation in Drosophila.

    PubMed

    Dunlap, David; Yokoyama, Ruth; Ling, Huiping; Sun, He-Ying; McGill, Kerry; Cugusi, Simona; Lucchesi, John C

    2012-12-01

    The regulatory mechanism of dosage compensation is the paramount example of epigenetic regulation at the chromosomal level. In Drosophila, this mechanism, designed to compensate for the difference in the dosage of X-linked genes between the sexes, depends on the MSL complex that enhances the transcription of the single dose of these genes in males. We have investigated the function of various subunits of the complex in mediating dosage compensation. Our results confirm that the highly enriched specific acetylation of histone H4 at lysine 16 of compensated genes by the histone acetyl transferase subunit MOF induces a more disorganized state of their chromatin. We have determined that the association of the MSL complex reduces the level of negative supercoiling of the deoxyribonucleic acid of compensated genes, and we have defined the role that the other subunits of the complex play in this topological modification. Lastly, we have analyzed the potential contribution of ISWI-containing remodeling complexes to the architecture of compensated chromatin, and we suggest a role for this remodeling factor in dosage compensation.

  14. Ease of opening of blistered solid dosage forms in a senior citizens target group.

    PubMed

    Braun-Münker, Myriam; Ecker, Felix

    2016-10-30

    Blisters differing in design and handling are established as packaging material for solid dosage forms. The ease of opening of blisters influences application and patient's compliance. In this study the influence of visibility and movability of solid dosage forms in blister packaging on both, easy opening and patient's satisfaction, were investigated by target group testing according to ONR CEN/TS 15945. For each testing 20 participants in the age of 65-80 years were recruited randomly. They opened the blisters on realistic terms without any auxiliary devices. Video documentation of the hands' movements was recorded to analyze the opening procedure. To show the influence of visibility of the dosage form in the blister, capsules size 1 were packed in transparent and opaque blisters. A moderate influence of the visibility on both, the ease of opening and patient satisfaction, was observed. A second study dealt with the movability of solid dosage forms in blisters. Therefore, three different sizes of tablets with similar shapes were packed in identical cavities. Limited movability was found as major criterion on effectiveness and effectivity of opening as well as on satisfaction with the opening procedure.

  15. 21 CFR 500.26 - Timed-release dosage form drugs.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... approved new animal drug application, or listed in the index, as required by paragraph (a) of this section... of such articles. A new animal drug application or index listing is required in any such case. (d... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Timed-release dosage form drugs. 500.26...

  16. 10 CFR 35.2063 - Records of dosages of unsealed byproduct material for medical use.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... medical use. 35.2063 Section 35.2063 Energy NUCLEAR REGULATORY COMMISSION MEDICAL USE OF BYPRODUCT MATERIAL Records § 35.2063 Records of dosages of unsealed byproduct material for medical use. (a) A... must contain— (1) The radiopharmaceutical; (2) The patient's or human research subject's name,...

  17. Genes That Implement the Hermaphrodite Mode of Dosage Compensation in Caenorhabditis Elegans

    PubMed Central

    Plenefisch, J. D.; DeLong, L.; Meyer, B. J.

    1989-01-01

    We report a genetic characterization of several essential components of the dosage compensation process in Caenorhabditis elegans. Mutations in the genes dpy-26, dpy-27, dpy-28, and the newly identified gene dpy-29 disrupt dosage compensation, resulting in elevated X-linked gene expression in XX animals and an incompletely penetrant maternal-effect XX-specific lethality. These dpy mutations appear to cause XX animals to express each set of X-linked genes at a level appropriate for XO animals. XO dpy animals are essentially wild type. Both the viability and the level of X-linked gene expression in XX animals carrying mutations in two or more dpy genes are the same as in animals carrying only a single mutation, consistent with the view that these genes act together in a single process (dosage compensation). To define a potential time of action for the gene dpy-28 we performed reciprocal temperature-shift experiments with a heat sensitive allele. The temperature-sensitive period for lethality begins 5 hr after fertilization at the 300-cell stage and extends to about 9 hr, a point well beyond the end of cell proliferation. This temperature-sensitive period suggests that dosage compensation is functioning in XX animals by mid-embryogenesis, when many zygotically transcribed genes are active. While mutations in the dpy genes have no effect on the sexual phenotype of otherwise wild-type XX or XO animals, they do have a slight feminizing effect on animals whose sex-determination process is already genetically perturbed. The opposite directions of the feminizing effects on sex determination and the masculinizing effects on dosage compensation caused by the dpy mutations are inconsistent with the wild-type dpy genes acting to coordinately control both processes. Instead, the feminizing effects are most likely an indirect consequence of disruptions in dosage compensation caused by the dpy mutations. Based on the cumulative evidence, the likely mechanism of dosage compensation

  18. Comparison of Amikacin Pharmacokinetics in Neonates Following Implementation of a New Dosage Protocol

    PubMed Central

    Johnson, Peter N.; Anderson, Michael P.; Sekar, Kris C.; Welliver, Robert C.; Miller, Jamie L.

    2017-01-01

    OBJECTIVES The primary aim was to compare attainment of goal serum amikacin concentrations using two dosage regimens in patients admitted to a neonatal intensive care unit. Secondary objectives included comparison of percentages of supratherapeutic trough concentrations, and subtherapeutic and supratherapeutic peak concentrations. METHODS This was an Institutional Review Board–approved, retrospective study of neonates receiving amikacin during January–December 2013 (group 1) and January–December 2014 (group 2). Group 1 received amikacin dosage consistent with published recommendations, whereas group 2 was dosed using a modified protocol that was based on postmenstrual and postnatal age. Goal serum amikacin peak concentration was defined as 20 to 35 mg/L; hence, subtherapeutic and supratherapeutic peak concentrations were defined as <20 mg/L and >35 mg/L, respectively. Supratherapeutic trough concentrations were >8 mg/L. Between-group analysis was performed using Wilcoxon-Mann-Whitney test, Student t-test or χ2, or Fisher exact analysis as appropriate with a p value <0.05. RESULTS A total of 278 neonates were included (group 1: n = 144; group 2: n = 134). Most patients were male (60%) and were admitted for prematurity or respiratory distress (77%). The median gestational age in group 1 was 34.4 weeks (range, 30.0–37.9 weeks) versus group 2 at 36.9 weeks (range, 31.4–38.9 weeks), whereas the postnatal age was similar between both groups at 4 days. There was a significant increase in attaining goal peak amikacin concentrations between groups 1 and 2, 34% versus 84%, p < 0.001, and decrease in supratherapeutic peak concentrations, 65% versus 12%, p < 0.001. There was no significant difference in subtherapeutic peak or supratherapeutic trough concentrations. CONCLUSIONS A modified neonatal amikacin dosage protocol resulted in increased peak amikacin serum concentration compared with published dosage recommendations. Future research should focus on

  19. Analyse du comportement thermique du sol d'une serre agricole par simulation dynamique

    NASA Astrophysics Data System (ADS)

    Monteil, C.; Amouroux, M.

    1997-02-01

    The overall energetical behaviour of a greenhouse is significantly affected by diurnal storage and nocturnal release of energy inside the soil, which is the only element with high thermal capacitance. Its specific part is analysed with a pre-existing dynamic simulation model. The first part of this paper studies the effects of 4kinds of heating exchangers along each month of an entire cultivation period: hot air convector, aerial metallic pipes with hot water circulation, radiant mulch or buried pipes with warm water circulation. The second part develops the hourly behaviour of both greenhouse and soil during a cold standard-day with each of the 4exchangers. The third part is a sensibility study to various classes of factors in the case of hot air convector exchanger: climatic environment, control policy, intrinsic properties of the greenhouse (soil characteristics, crop density, cover transparency). Le comportement énergétique global d'une serre agricole est influencé de manière parfois importante par le stockage diurne et la restitution nocturne d'énergie au sein de son sol, seul élément à grande capacité thermique. Le rôle spécifique joué par le sol est analysé en appliquant un modèle de simulation dynamique déjà existant. Une première partie compare les effets de 4types d'échangeurs de chauffage sur chaque mois d'une période de culture : aérotherme, tubes aériens à circulation d'eau chaude, paillage radiant ou tubes enterrés à circulation d'eau tiède. Une seconde partie développe le comportement horaire de la serre et du sol pour une journée-type froide en présence de chacun des échangeurs. Une troisième partie précise la sensibilité du bilan thermique de la serre et du sol à différents types de facteurs dans le cas d'un échangeur par aérotherme: environnement climatique, politique de contrôle de la serre, propriétés intrinsèques de la serre (caractéristiques du sol, densité de culture, transparence de la couverture).

  20. Dosage Effect and the Efficacy of a Video-Based Teamwork-Building Series with Urban Elementary School Children

    ERIC Educational Resources Information Center

    Mokrue, Kathariya; Elias, Maurice J.; Bry, Brenna H.

    2005-01-01

    This study examines the role of implementation dosage in the effectiveness of a school-based social and emotional skills building curriculum, The Talking with TJ video series, among urban, predominantly minority elementary school children. It was hypothesized that children in higher dosage schools will exhibit greater improvements in their social…

  1. [Pharmacokinetic and analgesic properties of the injectable dosage form of a new imidazobenzimidazole derivative RU-1205 with kappa agonist activity].

    PubMed

    Spasov, A A; Smirnova, L A; Grechko, O U; Raschenko, A I; Shtareva, D M; Anisimova, V A

    2015-01-01

    Pharmacokinetic properties of imidazobenzimidazole derivative compound RU-1205 were investigated after subcutaneous administration to rabbits as a substance and a dosage form (lyophilisates for injection) at a dose of 25 mg/kg. The lyophilisate was characterized by high values of the relative bioavailability. In tests, the "hot plate" and "vinegar cramps" the dosage form and the substance exhibited the same analgesic effect.

  2. Genes and small RNA transcripts exhibit dosage-dependent expression pattern in maize copy-number alterations

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Copy-number alterations are widespread in animal and plant genomes, but their immediate impact on gene expression is still unclear. In animals, copy-number alterations usually exhibit dosage effects, except for sex chromosomes that tend to be dosage compensated. In plants, genes within small duplica...

  3. 78 FR 3900 - Generic Drug User Fee-Active Pharmaceutical Ingredient and Finished Dosage Form Facility Fee...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-01-17

    ... HUMAN SERVICES Food and Drug Administration Generic Drug User Fee--Active Pharmaceutical Ingredient and... drug active pharmaceutical ingredient (API) and finished dosage form (FDF) facilities user fees for... applications in the backlog as of October 1, 2012, on finished dosage form (FDF) and active...

  4. Cri du chat syndrome: a critical review.

    PubMed

    Rodríguez-Caballero, Angela; Torres-Lagares, Daniel; Rodríguez-Pérez, Antonio; Serrera-Figallo, María-Angeles; Hernández-Guisado, José-María; Machuca-Portillo, Guillermo

    2010-05-01

    A new syndrome was identified in 1963, when Lejeune et al. reported a genetic disease resulting from a partial or total deletion on the short arm of chromosome 5 (5p-) and named it the cri du chat syndrome (CdCS). This term makes reference to the main clinical feature of the syndrome, a high-pitched monochromatic cat-like crying, that usually disappears in the first years of life. CdCS is one of the most common chromosomal deletion syndromes in humans, with an incidence of 1:15.000-1:50.000 live-births. Our purpose was to review different aspects of this syndrome (concept, epidemiology, aetiology, clinical features, diagnostic methods and prognosis) emphasizing both: the breakthrough in this field introduced by new cytogenetic and molecular techniques, and the orofacial manifestations most frequently reported. The main orofacial anomalies registered were mandibular microretrognathia, high palate but rarely cleft, variable malocclusion (frequently anterior open-bite), enamel hypoplasia, poor oral hygiene, generalized chronic periodontitis, and retardation of tooth eruption, although there is not enough evidence to support any clear association between these pathologies and the CdCS.

  5. [Investigation of acupoints on Du (governor) channel].

    PubMed

    Zhang, Jian-bin; Wang, Ling-ling

    2006-07-01

    The origin and variation of acupoints on the Du channel are investigated by analyzing and studying the number and distribution of points recorded in the ancient medical works. It is found that the amount and distribution of the points were different in different ages. The distributions of the points were not only located on the midline of the face, head, nape and posterior midline but also on both sides of the spine from the period of Neijing (Inner Canon) to that of Zhenjiu Jiayi Jing (A-B Classic of Acupuncture and Moxibustion). Since the period of Tongren Shuxue Zhenjiu Tujing (Illustration Classic of Acupoints on Bronze Statue) in the Song dynasty, only those points of the midline from the face, nape to the spine are remained there until now. Meanwhile, the amount of points were also varied because of the cognition to the points on the spine. Huangdi Neijing Taisu (Grand Simplicity of Inner Canon of Huangdi) compiled in the Tang Dynasty first mentioned the arguments about the varied points on the channel. The records by Yang Shangshan and Wang Bing indicate that the main differences on the cognition of the channel andits points appeared during the period of the Tang Dynasty to the Song Dynasty.

  6. Mise à jour sur le nouveau vaccin 9-valent pour la prévention du virus du papillome humain

    PubMed Central

    Yang, David Yi; Bracken, Keyna

    2016-01-01

    Résumé Objectif Informer les médecins de famille quant à l’efficacité, à l’innocuité, aux effets sur la santé publique et à la rentabilité du vaccin 9-valent contre le virus du papillome humain (VPH). Qualité des données Des articles pertinents publiés dans PubMed jusqu’en mai 2015 ont été examinés et analysés. La plupart des données citées sont de niveau I (essais randomisés et contrôlés et méta-analyses) ou de niveau II (études transversales, cas-témoins et épidémiologiques). Des rapports et recommandations du gouvernement sont aussi cités en référence. Message principal Le vaccin 9-valent contre le VPH, qui offre une protection contre les types 6, 11, 16, 18, 31, 33, 45, 52 et 58 du VPH, est sûr et efficace et réduira encore plus l’incidence des infections à VPH, de même que les cas de cancer lié au VPH. Il peut également protéger indirectement les personnes non immunisées par l’entremise du phénomène d’immunité collective. Un programme d’immunisation efficace peut prévenir la plupart des cancers du col de l’utérus. Les analyses montrent que la rentabilité du vaccin 9-valent chez les femmes est comparable à celle du vaccin quadrivalent original contre le VPH (qui protège contre les types 6, 11, 16 et 18 du VPH) en usage à l’heure actuelle. Toutefois, il faut investiguer plus en profondeur l’utilité d’immuniser les garçons avec le vaccin 9-valent contre le VPH. Conclusion en plus d’être sûr, le vaccin 9-valent protège mieux contre le VPH que le vaccin quadrivalent. Une analyse coûtefficacité en favorise l’emploi, du moins chez les adolescentes. Ainsi, les médecins devraient recommander le vaccin 9-valent à leurs patients plutôt que le vaccin quadrivalent contre le VPH.

  7. [Post-marketing re-evaluation about usage and dosage of Chinese medicine based on human population pharmacokinetics].

    PubMed

    Jiang, Junjie; Xie, Yanming

    2011-10-01

    The usage and dosage of Chinese patent medicine are determined by rigorous evaluation which include four clinical trail stages: I, II, III. But the usage and dosage of Chinese patent medicine are lacked re-evaluation after marketing. And this lead to unchanging or fixed of the usage and dosage of Chinese patent medicine instead of different quantity based on different situations in individual patients. The situation of Chinese patent medicine used in clinical application is far away from the idea of the "Treatment based on syndrome differentiation" in traditional Chinese medicine and personalized therapy. Human population pharmacokinetics provides data support to the personalized therapy in clinical application, and achieved the postmarking reevaluating of the usage and dosage of Chinese patent medicine. This paper briefly introduced the present situation, significance and the application of human population pharmacokinetics about re-evaluation of the usage and dosage of Chinese patent medicine after marketing.

  8. Impact of release characteristics of sinomenine hydrochloride dosage forms on its pharmacokinetics in beagle dogs

    PubMed Central

    Sun, Jin; Shi, Jie-Ming; Zhang, Tian-Hong; Gao, Kun; Mao, Jing-Jing; Li, Bing; Sun, Ying-Hua; He, Zhong-Gui

    2005-01-01

    AIM: To investigate the effect of release behavior of sustained-release dosage forms of sinomenine hydrochloride (SM•HCl) on its pharmacokinetics in beagle dogs. METHODS: The in vitro release behavior of two SM•HCl dosage forms, including commercial 12-h sustained-release tablets and 24-h sustained-release pellets prepared in our laboratory, was examined. The two dosage forms were orally administrated to beagle dogs, and then the in vivo SM•HCl pharmacokinetics was investigated and compared. RESULTS: The optimal SM•HCl sustained-release formulation was achieved by mixing slow- and rapid-release pellets (9:1, w/w). The SM•HCl release profiles of the sustained-release pellets were scarcely influenced by the pH of the dissolution medium. Release from the 12-h sustained-release tablets was markedly quicker than that from the 24-h sustained-release pellets, the cumulative release up to 12-h was 99.9% vs 68.7%. From a pharmacokinetic standpoint, the 24-h SM•HCl sustained-release pellets had longer tmax and lower Cmax compared to the 12-h sustained-release tablets, the tmax being 2.67×0.52 h vs 9.83×0.98 h and the Cmax being 1 334.45±368.76 ng/mL vs 893.12±292.55 ng/mL, respectively. However, the AUC0-tn of two SM•HCl dosage forms was comparable and both preparations were statistically bioequivalent. Furthermore, the two preparations had good correlations between SM•HCl percentage absorption in vivo and the cumulative percentage release in vitro. CONCLUSION: The in vitro release properties of the dosage forms strongly affect their pharmacokinetic behavior in vivo. Therefore, managing the in vitro release behavior of dosage forms is a promising strategy for obtaining the optimal in vivo pharmacokinetic characteristics and safe therapeutic drug concentration-time curves. PMID:16052686

  9. Effect of norepinephrine dosage and calibration frequency on accuracy of pulse contour-derived cardiac output

    PubMed Central

    2011-01-01

    Introduction Continuous cardiac output monitoring is used for early detection of hemodynamic instability and guidance of therapy in critically ill patients. Recently, the accuracy of pulse contour-derived cardiac output (PCCO) has been questioned in different clinical situations. In this study, we examined agreement between PCCO and transcardiopulmonary thermodilution cardiac output (COTCP) in critically ill patients, with special emphasis on norepinephrine (NE) administration and the time interval between calibrations. Methods This prospective, observational study was performed with a sample of 73 patients (mean age, 63 ± 13 years) requiring invasive hemodynamic monitoring on a non-cardiac surgery intensive care unit. PCCO was recorded immediately before calibration by COTCP. Bland-Altman analysis was performed on data subsets comparing agreement between PCCO and COTCP according to NE dosage and the time interval between calibrations up to 24 hours. Further, central artery stiffness was calculated on the basis of the pulse pressure to stroke volume relationship. Results A total of 330 data pairs were analyzed. For all data pairs, the mean COTCP (±SD) was 8.2 ± 2.0 L/min. PCCO had a mean bias of 0.16 L/min with limits of agreement of -2.81 to 3.15 L/min (percentage error, 38%) when compared to COTCP. Whereas the bias between PCCO and COTCP was not significantly different between NE dosage categories or categories of time elapsed between calibrations, interchangeability (percentage error <30%) between methods was present only in the high NE dosage subgroup (≥0.1 μg/kg/min), as the percentage errors were 40%, 47% and 28% in the no NE, NE < 0.1 and NE ≥ 0.1 μg/kg/min subgroups, respectively. PCCO was not interchangeable with COTCP in subgroups of different calibration intervals. The high NE dosage group showed significantly increased central artery stiffness. Conclusions This study shows that NE dosage, but not the time interval between calibrations, has an

  10. Modelisation du Signal Radar EN Milieu Stratifie et Evaluation de Techniques de Mesure de L'humidite du Sol

    NASA Astrophysics Data System (ADS)

    Boisvert, Johanne

    La presente etude se penche sur des problemes relies a l'echantillonnage de l'humidite de sol et a l'estimation du signal radar sur sols nus. Le travail se divise en deux volets. Le volet 1 evalue trois techniques de mesure de l'humidite du sol (gravimetrie, reflectometrie temporelle et sonde dielectrique) et deux protocoles d'echantillonnage. Dans le volet 2, un modele de simulation du signal en milieu stratifie est developpe, et les estimes de signal obtenus sont compares aux estimes bases uniquement sur une valeur moyenne d'humidite du sol prise sur une profondeur fixe d'echantillonnage. Les differences entre les deux estimes dependent de la frequence et du choix judicieux de la profondeur d'echantillonnage; elles sont plus importantes aux faibles angles et en polarisation HV, puis VV. Le modele de simulation a aussi ete utilise pour etudier la profondeur de penetration du signal et en deduire la profondeur optimale d'echantillonnage en tenant compte des caracteristiques du signal. Une variation de 25 ^circ de l'angle d'incidence a peu d'effet sur la profondeur de penetration en bande Ku; l'ecart reste inferieur ou egal a 0,5 cm en bande C mais peut atteindre 1,3 cm en bande L. L'impact de la polarisation est nul en bande Ku mais croi t avec l'angle d'incidence en bande C et L. A 50^circ, il est, en moyenne de 1 cm en bande C et de 2 cm en bande L. En polarisation VV, la profondeur croi t avec une augmentation de l'angle alors que l'effet est inverse en polarisation HH. Deux methodes pour estimer la profondeur d'echantillonnage en conditions operationnelles sont presentees. Lorsqu'on inverse un modele pour estimer l'humidite du sol a partir du signal, ces methodes permettent aussi d'estimer l'epaisseur de sol representee par l'humidite ainsi estimee.

  11. Development and Validation of Simultaneous Spectrophotometric Methods for Drotaverine Hydrochloride and Aceclofenac from Tablet Dosage Form

    PubMed Central

    Shah, S. A.; Shah, D. R.; Chauhan, R. S.; Jain, J. R.

    2011-01-01

    Two simple spectrophotometric methods have been developed for simultaneous estimation of drotaverine hydrochloride and aceclofenac from tablet dosage form. Method I is a simultaneous equation method (Vierodt's method), wavelengths selected are 306.5 and 276 nm. Method II is the absorbance ratio method (Q-Analysis), which employs 298.5 nm as λ1 and 276 nm as λ2 (λmax of AF) for formation of equations. Both the methods were found to be linear between the range of 8-32 μg/ml for drotaverine and 10-40 μg/ml for aceclofenac. The accuracy and precision were determined and found to comply with ICH guidelines. Both the methods showed good reproducibility and recovery with % RSD in the desired range. The methods were found to be rapid, specific, precise and accurate and can be successfully applied for the routine analysis of drotaverine and aceclofenac in their combined tablet dosage form. PMID:22457554

  12. Shared risk evaluation mitigation strategy for all immediate-release transmucosal fentanyl dosage forms.

    PubMed

    2012-06-01

    The Food and Drug Administration approved a single shared Risk Evaluation Mitigation Strategy (REMS) for transmucosal immediate-release fentanyl dosage forms in December 2011. This report describes the goals, elements, and restricted distribution system of the REMS designed to reduce risk of abuse, misuse, addiction, and overdose with the drugs. Questions and answers about REMS also are presented. The U.S. Food and Drug Administration (FDA) announced a shared REMS for all immediate-release transmucosal fentanyl dosage forms on December 29, 2011, to become effective in March 2012. That announcement is accessible at: http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm285345.htm. Concurrently the FDA posted a series of questions and answers on this shared REMS at: http://http://www.fda.gov/Drugs/DrugSafety/InformationbyDrugClass/ucm284717.htm. Both documents are in the public domain.

  13. Influence of the fuel and dosage on the performance of double-compartment microbial fuel cells.

    PubMed

    Asensio, Y; Fernandez-Marchante, C M; Lobato, J; Cañizares, P; Rodrigo, M A

    2016-08-01

    This manuscript focuses on the evaluation of the use of different types and dosages of fuels in the performance of double-compartment microbial fuel cell equipped with carbon felt electrodes and cationic membrane. Five types of fuels (ethanol, glycerol, acetate, propionate and fructose) have been tested for the same organic load (5,000 mg L(-1) measured as COD) and for one of them (acetate), the range of dosages between 500 and 20,000 mg L(-1) of COD was also studied. Results demonstrate that production of electricity depends strongly on the fuel used. Carboxylic acids are much more efficient than alcohols or fructose for the same organic load and within the range 500-5,000 mg L(-1) of acetate the production of electricity increases linearly with the amount of acetate fed but over these concentrations a change in the population composition may explain a worse performance.

  14. Form and function of dosage-compensated chromosomes--a chicken-and-egg relationship.

    PubMed

    Grimaud, Charlotte; Becker, Peter B

    2010-08-01

    Does the three-dimensional (3D) conformation of interphase chromosomes merely reflect their function or does it actively contribute to gene regulation? The analysis of sex chromosomes that are subject to chromosome-wide dosage compensation processes promises new insight into this question. Chromosome conformations are dynamic and largely determined by association of distant chromosomal loci in the nuclear space or by their anchoring to the nuclear envelope, effectively generating chromatin loops. The type and extent of such interactions depend on chromatin-bound transcription regulators and therefore reflects function. Dosage compensation adjusts the overall transcription activity of X chromosomes to assure balanced expression in the two sexes. Initial analyses of mammalian and Drosophila X chromosomes have led to the hypothesis that their conformations may not only reflect their functional state but may in turn contribute to the coordination of chromosome-wide tuning of transcription.

  15. Using the technique of computed tomography for nondestructive analysis of pharmaceutical dosage forms

    NASA Astrophysics Data System (ADS)

    de Oliveira, José Martins, Jr.; Mangini, F. Salvador; Carvalho Vila, Marta Maria Duarte; ViníciusChaud, Marco

    2013-05-01

    This work presents an alternative and non-conventional technique for evaluatingof physic-chemical properties of pharmaceutical dosage forms, i.e. we used computed tomography (CT) technique as a nondestructive technique to visualize internal structures of pharmaceuticals dosage forms and to conduct static and dynamical studies. The studies were conducted involving static and dynamic situations through the use of tomographic images, generated by the scanner at University of Sorocaba - Uniso. We have shown that through the use of tomographic images it is possible to conduct studies of porosity, densities, analysis of morphological parameters and performing studies of dissolution. Our results are in agreement with the literature, showing that CT is a powerful tool for use in the pharmaceutical sciences.

  16. New onset somnambulism associated with different dosage of mirtazapine: a case report.

    PubMed

    Yeh, Yi-Wei; Chen, Chun-Hsiung; Feng, Hui-Ming; Wang, Sheng-Chiang; Kuo, Shin-Chang; Chen, Chih-Kang

    2009-01-01

    Somnambulism consists of variously complex behaviors that may result in harm to self or to others. Many different medications have been reported to induce somnambulism, and a few of them are newer antidepressants. A 40-year-old woman with history of major depression who experienced new onset somnambulism for successive 3 nights, whereas the antidepressant mirtazapine was increased from 30 to 45 mg/d. The notable and complex sleepwalking symptoms terminated dramatically on the first night after withdrawal of mirtazapine. There is clearly a cause-and-effect relationship between the treatment of higher-dosage mirtazapine and development of somnambulism. It might be related to the different affinities to 5-hydroxytryptamine 2 (5-HT(2)) and H(1) receptors at different dosages of mirtazapine, which explain the patient experiencing sleepwalking episodes exclusively at higher doses of mirtazapine. Clinical physicians should be aware of this adverse effect and taper or discontinue the regimen if sleepwalking develops.

  17. Dosage Compensation in Drosophila: Nadp-Enzyme Activities and Cross-Reacting Material

    PubMed Central

    Williamson, John H.; Bentley, Michael M.

    1983-01-01

    The relationships between gene dosage, enzyme activities and CRM levels have been determined for G6PD and 6PGD. Enzyme activities and CRM levels were directly proportional and increased in genotypes carrying duplications of the respective structural genes. When a duplication consisting of the distal 45% of the X chromosome was used to duplicate Pgd+, 6PGD activity and CRM increased and G6PD activity decreased. When the proximal 55% of the X chromosome was duplicated, G6PD activity and CRM increased whereas 6PGD activity and CRM levels decreased. These observations support the model of dosage compensation of X-linked genes that invokes an autosomal activator in limited concentrations for which X-linked loci compete. The distal 45% of the X chromosome, when duplicated, caused a significant increase in NADP-malic enzyme activity and CRM levels, as if a structural gene for NADP-ME is sex-linked. PMID:6406296

  18. Artificial neural networks in evaluation and optimization of modified release solid dosage forms.

    PubMed

    Ibrić, Svetlana; Djuriš, Jelena; Parojčić, Jelena; Djurić, Zorica

    2012-10-18

    Implementation of the Quality by Design (QbD) approach in pharmaceutical development has compelled researchers in the pharmaceutical industry to employ Design of Experiments (DoE) as a statistical tool, in product development. Among all DoE techniques, response surface methodology (RSM) is the one most frequently used. Progress of computer science has had an impact on pharmaceutical development as well. Simultaneous with the implementation of statistical methods, machine learning tools took an important place in drug formulation. Twenty years ago, the first papers describing application of artificial neural networks in optimization of modified release products appeared. Since then, a lot of work has been done towards implementation of new techniques, especially Artificial Neural Networks (ANN) in modeling of production, drug release and drug stability of modified release solid dosage forms. The aim of this paper is to review artificial neural networks in evaluation and optimization of modified release solid dosage forms.

  19. Gentamicin tissue concentration in various avian species following recommended dosage therapy

    USGS Publications Warehouse

    Bush, M.; Locke, D.; Neal, L.A.; Carpenter, J.W.

    1981-01-01

    Plasma and tissue drug concentrations were compared in eastern bobwhite quail (Colinus virginianus virginianus) and pigeons (Columba livia) given gentamicin by IM administration at the dosage of 10 mg/kg, and in greater sandhill cranes (Grus canadensis tabida) and hybrid rosybill ducks (Netta sp) given the same antibiotic at a dosage of 5 mg/kg. Quail and cranes had significantly higher liver concentrations of gentamicin at 6 hours after injection than did pigeons and ducks. Cranes had significantly higher plasma concentrations than did ducks at 6 hours after injection. Compared with plasma values, gentamicin concentrations were significantly higher in the liver of cranes at 12 hours after injection, and in the kidneys at 18 hours.

  20. Dosage sensitivity is a major determinant of human copy number variant pathogenicity

    PubMed Central

    Rice, Alan M.; McLysaght, Aoife

    2017-01-01

    Human copy number variants (CNVs) account for genome variation an order of magnitude larger than single-nucleotide polymorphisms. Although much of this variation has no phenotypic consequences, some variants have been associated with disease, in particular neurodevelopmental disorders. Pathogenic CNVs are typically very large and contain multiple genes, and understanding the cause of the pathogenicity remains a major challenge. Here we show that pathogenic CNVs are significantly enriched for genes involved in development and genes that have greater evolutionary copy number conservation across mammals, indicative of functional constraints. Conversely, genes found in benign CNV regions have more variable copy number. These evolutionary constraints are characteristic of genes in pathogenic CNVs and can only be explained by dosage sensitivity of those genes. These results implicate dosage sensitivity of individual genes as a common cause of CNV pathogenicity. These evolutionary metrics suggest a path to identifying disease genes in pathogenic CNVs. PMID:28176757

  1. Structural basis for MOF and MSL3 recruitment into the dosage compensation complex by MSL1.

    PubMed

    Kadlec, Jan; Hallacli, Erinc; Lipp, Michael; Holz, Herbert; Sanchez-Weatherby, Juan; Cusack, Stephen; Akhtar, Asifa

    2011-02-01

    The male-specific lethal (MSL) complex is required for dosage compensation in Drosophila melanogaster, and analogous complexes exist in mammals. We report structures of binary complexes of mammalian MSL3 and the histone acetyltransferase (HAT) MOF with consecutive segments of MSL1. MSL1 interacts with MSL3 as an extended chain forming an extensive hydrophobic interface, whereas the MSL1-MOF interface involves electrostatic interactions between the HAT domain and a long helix of MSL1. This structure provides insights into the catalytic mechanism of MOF and enables us to show analogous interactions of MOF with NSL1. In Drosophila, selective disruption of Msl1 interactions with Msl3 or Mof severely affects Msl1 targeting to the body of dosage-compensated genes and several high-affinity sites, without affecting promoter binding. We propose that Msl1 acts as a scaffold for MSL complex assembly to achieve specific targeting to the X chromosome.

  2. Biowaiver monographs for immediate release solid oral dosage forms: metoclopramide hydrochloride.

    PubMed

    Stosik, A G; Junginger, H E; Kopp, S; Midha, K K; Shah, V P; Stavchansky, S; Dressman, J B; Barends, D M

    2008-09-01

    Literature data are reviewed relevant to the decision for a biowaiver of immediate release (IR) solid oral dosage forms containing metoclopramide hydrochloride. In addition, new solubility data, obtained under Biopharmaceutics Classification System (BCS) conditions are presented. Metoclopramide HCl is conservatively assigned to BCS Class III. Taken also into consideration excipient interactions reported in metoclopramide drug products, its pharmacokinetic properties and therapeutic use and therapeutic index, a biowaiver can be recommended when: (a) the test product contains only excipients present also in metoclopramide HCl containing IR solid oral drug products approved in ICH or associated countries, for instance as presented in this paper, (b) in amounts in normal use in IR solid oral dosage forms, and (c) the test product and the comparator both comply with the criteria for very rapidly dissolving.

  3. Biowaiver monographs for immediate release solid oral dosage forms: quinidine sulfate.

    PubMed

    Grube, S; Langguth, P; Junginger, H E; Kopp, S; Midha, K K; Shah, V P; Stavchansky, S; Dressman, J B; Barends, D M

    2009-07-01

    Literature data are reviewed relevant to the decision to allow a waiver of in vivo bioequivalence (BE) testing for the approval of new multisource and reformulated immediate release (IR) solid oral dosage forms containing quinidine sulfate. Quinidine sulfate's solubility and permeability, its therapeutic use and index, pharmacokinetics, excipient interactions and reported BE/bioavailability (BA) problems were taken into consideration. The available data are not fully conclusive, but do suggest that quinidine sulfate is highly soluble and moderately to highly permeable and would likely be assigned to BCS Class I (or at worst BCS III). In view of the inconclusiveness of the data and, more important, quinidine's narrow therapeutic window and critical indication, a biowaiver based approval of quinidine containing dosage forms cannot be recommended for either new multisource drug products or for major postapproval changes (variations) to existing drug products.

  4. Biowaiver monographs for immediate release solid oral dosage forms: ciprofloxacin hydrochloride.

    PubMed

    Olivera, M E; Manzo, R H; Junginger, H E; Midha, K K; Shah, V P; Stavchansky, S; Dressman, J B; Barends, D M

    2011-01-01

    Literature data relevant to the decision to allow a waiver of in vivo bioequivalence (BE) testing for the approval of new multisource and reformulated immediate release (IR) solid oral dosage forms containing ciprofloxacin hydrochloride as the only active pharmaceutical ingredient (API) are reviewed. Ciprofloxacin hydrochloride's solubility and permeability, its therapeutic use and index, pharmacokinetics, excipient interactions and reported BE/bioavailability (BA) problems were taken into consideration. Solubility and BA data indicate that ciprofloxacin hydrochloride is a BCS Class IV drug. Therefore, a biowaiver based approval of ciprofloxacin hydrochloride containing IR solid oral dosage forms cannot be recommended for either new multisource drug products or for major scale-up and postapproval changes (variations) to existing drug products.

  5. Biowaiver Monographs for Immediate-Release Solid Oral Dosage Forms: Nifedipine.

    PubMed

    Gajendran, Jayachandar; Krämer, Johannes; Shah, Vinod P; Langguth, Peter; Polli, James; Mehta, Mehul; Groot, D W; Cristofoletti, Rodrigo; Abrahamsson, Bertil; Dressman, Jennifer B

    2015-10-01

    Literature data relevant to the biopharmaceutical properties of the active pharmaceutical ingredient (API) nifedipine are reviewed to evaluate whether a waiver of in vivo bioequivalence (BE) testing of immediate-release (IR) dosage forms formulated as tablets and soft gelatin capsules is warranted. Nifedipine's solubility and permeability, its therapeutic use and index, pharmacokinetics, food drug interactions, and any reported BE/bioavailability problems were all taken into consideration. Solubility and BA data indicate conclusively that nifedipine is a class II substance of biopharmaceutics classification system (BCS) and that the formulation of drug product plays a key role on the dissolution characteristics of the API. Therefore, a BCS biowaiver-based approval of nifedipine containing IR oral dosage forms cannot be recommended for reformulated/new multisource drug products or for major scale-up and postapproval changes to the existing drug products.

  6. Particle Engineering Via Mechanical Dry Coating in the Design of Pharmaceutical Solid Dosage Forms.

    PubMed

    Qu, Li; Morton, David A V; Zhou, Qi Tony

    2015-01-01

    Cohesive powders are problematic in the manufacturing of pharmaceutical solid dosage forms because they exhibit poor flowability, fluidization and aerosolization. These undesirable bulk properties of cohesive powders represent a fundamental challenge in the design of efficient pharmaceutical manufacturing processes. Recently, mechanical dry coating has attracted increasing attention as it can improve the bulk properties of cohesive powders in a cheaper, simpler, safer and more environment-friendly way than the existing solvent-based counterparts. In this review, mechanical dry coating techniques are outlined and their potential applications in formulation and manufacturing of pharmaceutical solid dosage forms are discussed. Reported data from the literature have shown that mechanical dry coating holds promise for the design of superior pharmaceutical solid formulations or manufacturing processes by engineering the interfaces of cohesive powders in an efficient and economical way.

  7. Green approach towards the determination of hydroxyzine dihydrochloride in pure and pharmaceutical dosage forms.

    PubMed

    Mumtaz, Amina; Hussain, Shahid; Yasir, Muhammad

    2014-09-01

    A simple eco-friendly method has been developed for detection of hydroxyzine dihydrochloride in pure and pharmaceutical dosage forms. Both conventional system and microwave assisted procedures are used for the development of color. The blue coloured complex is measured spectrophotometrically at 750nm. Peak shift in FT-IR spectra also indicated the formation of complex. The reaction obeys Beer's law over the concentration range of 50- 250βg/mL of hydroxyzine dihydrochloride. The precision value (intra-day and inter-day RSD) for the drug is not greater than 0.79% and recoveries were found to be in range of 99.01-99.99%. The designed method is applicable for periodic determination of hydroxyzine dihydrochloride in pure and pharmaceutical dosage forms.

  8. Understanding pharmaceutical polymorphic transformations II: crystallization variables and influence on dosage forms.

    PubMed

    Sood, Jatin; Sapra, Bharti; Bhandari, Sameer; Tiwary, Ashok K

    2015-01-01

    Excipients or formulation variables have often been exploited to improve stability, modify release, or improve physicochemical properties of dosage forms. In pharmaceutical field, it is generally expected that excipients work at macromolecular level where they might influence the crystal structure of a solid. These polymers/colloidal particles may modify the rate and direction of crystal growth. It has also been observed, that different polymorphic crystals exhibit different colors on exposure to same colorant, predominantly due to difference in surface pH of different crystal lattices. Apart from physicochemical affect, crystal habit also influences pharmacokinetic parameters of the dosage form. Crystals with smaller size or lower lattice energy have shown to exhibit higher bioavailability with faster rate of release.

  9. Dry coating, a novel coating technology for solid pharmaceutical dosage forms.

    PubMed

    Luo, Yanfeng; Zhu, Jesse; Ma, Yingliang; Zhang, Hui

    2008-06-24

    Dry coating is a coating technology for solid pharmaceutical dosage forms derived from powder coating of metals. In this technology, powdered coating materials are directly coated onto solid dosage forms without using any solvent, and then heated and cured to form a coat. As a result, this technology can overcome such disadvantages caused by solvents in conventional liquid coating as serious air pollution, high time- and energy-consumption and expensive operation cost encountered by liquid coating. Several dry coating technologies, including plasticizer-dry-coating, electrostatic-dry-coating, heat-dry-coating and plasticizer-electrostatic-heat-dry-coating have been developed and extensively reported. This mini-review summarized the fundamental principles and coating processes of various dry coating technologies, and thoroughly analyzed their advantages and disadvantages as well as commercialization potentials.

  10. Derivative spectrophotometric method for simultaneous determination of clindamycin phosphate and tretinoin in pharmaceutical dosage forms.

    PubMed

    Barazandeh Tehrani, Maliheh; Namadchian, Melika; Fadaye Vatan, Sedigheh; Souri, Effat

    2013-04-10

    A derivative spectrophotometric method was proposed for the simultaneous determination of clindamycin and tretinoin in pharmaceutical dosage forms. The measurement was achieved using the first and second derivative signals of clindamycin at (1D) 251 nm and (2D) 239 nm and tretinoin at (1D) 364 nm and (2D) 387 nm.The proposed method showed excellent linearity at both first and second derivative order in the range of 60-1200 and 1.25-25 μg/ml for clindamycin phosphate and tretinoin respectively. The within-day and between-day precision and accuracy was in acceptable range (CV<3.81%, error<3.20%). Good agreement between the found andadded concentrations indicates successful application of the proposed method for simultaneous determination of clindamycin and tretinoin in synthetic mixtures and pharmaceutical dosage form.

  11. Chlorambucil dosage in frequently relapsing nephrotic syndrome: a controlled clinical trial.

    PubMed

    Baluarte, H J; Hiner, L; Gruskin, A B

    1978-02-01

    A controlled clinical trial was performed using two dosage regimens of chlorambucil to treat children with frequently relapsing nephrotic syndrome. All children concurrently received prednisone (60 mg/m2 on alternate days). Ten children (Group I) were given chlorambucil as a stable dose (0.2 mg/kg/day) for 56 to 60 days, and 11 children (Group II) received increasing doses (0.2 to 0.63 mg/kg/day) for 42 to 77 days. Two children in each group subsequently relapsed. Follow-up averaged 28.6 and 27.2 months in Groups I and II, respectively. Three children in Group II developed infectious complications. The data indicate that a stable dosage regimen for chlorambucil is as effective as an increasing dose regimen in achieving long-term remission of frequently relapsing nephrotic syndrome.

  12. La chirurgie du diaphragme sous aortique

    PubMed Central

    Moutakiallah, Younes; Maaroufi, Ilham; Aithoussa, Mahdi; Bamous, Mehdi; Abdou, Abdessamad; Atmani, Noureddine; Hatim, Abdedaïm; Amahzoune, Brahim; Bekkali, Youssef El; Boulahya, Abdelatif

    2016-01-01

    Le diaphragme sous aortique se caractérise par une certaine latence clinique et une faible morbi-mortalité. La chirurgie reste le traitement de choix malgré un réel risque de récurrence à long terme. Nous rapportons 18 patients opérés entre Avril 1994 et Mars 2011 pour diaphragme sous aortique d’âge moyen de 18,1±9,7 ans avec 11 patients de sexe masculin. Le diaphragme était de nature fibreuse chez 13 patients et fibro-musculaire chez 5 patients. Tous les patients ont été opérés par résection de diaphragme associée à une myectomie, une plastie aortique, une fermeture de communication interventriculaire et une ligature de canal artériel perméable respectivement chez 3, 3, 2 et 2 patients. La Mortalité opératoire était nulle et sans aucun cas de trouble de conduction postopératoire. Le suivi a duré en moyenne 44,3±36,8 mois sans aucun décès tardif. Deux patients ont présenté une récidive de diaphragme qui a nécessité une réopération avec bonne évolution. La tendance actuelle dans la chirurgie du diaphragme se fait vers des interventions précoces et des résections plus extensives. Cependant, le risque de récidive impose une surveillance échographique systématique et rapprochée. PMID:27516830

  13. The status of dosage compensation in the multiple X chromosomes of the platypus.

    PubMed

    Deakin, Janine E; Hore, Timothy A; Koina, Edda; Marshall Graves, Jennifer A

    2008-07-25

    Dosage compensation has been thought to be a ubiquitous property of sex chromosomes that are represented differently in males and females. The expression of most X-borne genes is equalized between XX females and XY males in therian mammals (marsupials and "placentals") by inactivating one X chromosome in female somatic cells. However, compensation seems not to be strictly required to equalize the expression of most Z-borne genes between ZZ male and ZW female birds. Whether dosage compensation operates in the third mammal lineage, the egg-laying monotremes, is of considerable interest, since the platypus has a complex sex chromosome system in which five X and five Y chromosomes share considerable genetic homology with the chicken ZW sex chromosome pair, but not with therian XY chromosomes. The assignment of genes to four platypus X chromosomes allowed us to examine X dosage compensation in this unique species. Quantitative PCR showed a range of compensation, but SNP analysis of several X-borne genes showed that both alleles are transcribed in a heterozygous female. Transcription of 14 BACs representing 19 X-borne genes was examined by RNA-FISH in female and male fibroblasts. An autosomal control gene was expressed from both alleles in nearly all nuclei, and four pseudoautosomal BACs were usually expressed from both alleles in male as well as female nuclei, showing that their Y loci are active. However, nine X-specific BACs were usually transcribed from only one allele. This suggests that while some genes on the platypus X are not dosage compensated, other genes do show some form of compensation via stochastic transcriptional inhibition, perhaps representing an ancestral system that evolved to be more tightly controlled in placental mammals such as human and mouse.

  14. Treatment of Vasospasm Secondary to Subarachnoid Hemorrhage Using Intra-Arterial Nimodipine in Low Dosage

    PubMed Central

    Bandeira, A.; Ribeiro, C.; Reis, J.

    2007-01-01

    Summary There are currently no consensus criteria to define the dosage of intra-arterial Nimodipine to be used to obtain permanent remission of vasospasm secondary to subarachnoid haemorrhage. The purpose of this paper is to establish a mathematical relation between the number of vessels affected by this kind of vasospasm and the Nimodipine dose that must be used for intra-arterial angioplasty to obtain permanent remission of the vasospasm. PMID:20566112

  15. A case of Pelizaeus-Merzbacher disease showing increased dosage of the proteolipid protein gene.

    PubMed

    Harding, B; Ellis, D; Malcolm, S

    1995-04-01

    Clinical, neuropathological and molecular genetic studies in a 9 month old boy with Pelizaeus-Merzbacher disease are described. The principal clinical features were developmental delay, nystagmus, stridor and seizures. Both brain and spinal cord showed almost complete absence of stainable central myelin, while cranial and spinal root myelin was preserved. Probes for cDNA in the boy and his asymptomatic mother indicated an increase in the dosage of proteolipid protein gene (of at least twofold) compared with controls.

  16. Materials for pharmaceutical dosage forms: molecular pharmaceutics and controlled release drug delivery aspects.

    PubMed

    Mansour, Heidi M; Sohn, Minji; Al-Ghananeem, Abeer; Deluca, Patrick P

    2010-09-15

    Controlled release delivery is available for many routes of administration and offers many advantages (as microparticles and nanoparticles) over immediate release delivery. These advantages include reduced dosing frequency, better therapeutic control, fewer side effects, and, consequently, these dosage forms are well accepted by patients. Advances in polymer material science, particle engineering design, manufacture, and nanotechnology have led the way to the introduction of several marketed controlled release products and several more are in pre-clinical and clinical development.

  17. Updating a Dosage-Effect Relationship for the Prevalence of Annoyance Due to General Transportation Noise

    DTIC Science & Technology

    1989-12-15

    sites near 7 U.S. Air Force bases. Borsky used automatic equipment to measure exposure in units of Ldn for approximately 10 days per site. A...Human Systems Division Air Force Systems Command Brooks Air Force Base, TX 78235-5000 90 n2 26 129 NOTICES When Government drawings, specifications, or...surveys. The Air Porce has come to rely heavily on this quantitative dosage-effect relationship for oredic- tirz aircraft noise-induced annoyance in

  18. The Status of Dosage Compensation in the Multiple X Chromosomes of the Platypus

    PubMed Central

    Deakin, Janine E.; Hore, Timothy A.; Koina, Edda; Marshall Graves, Jennifer A.

    2008-01-01

    Dosage compensation has been thought to be a ubiquitous property of sex chromosomes that are represented differently in males and females. The expression of most X-borne genes is equalized between XX females and XY males in therian mammals (marsupials and “placentals”) by inactivating one X chromosome in female somatic cells. However, compensation seems not to be strictly required to equalize the expression of most Z-borne genes between ZZ male and ZW female birds. Whether dosage compensation operates in the third mammal lineage, the egg-laying monotremes, is of considerable interest, since the platypus has a complex sex chromosome system in which five X and five Y chromosomes share considerable genetic homology with the chicken ZW sex chromosome pair, but not with therian XY chromosomes. The assignment of genes to four platypus X chromosomes allowed us to examine X dosage compensation in this unique species. Quantitative PCR showed a range of compensation, but SNP analysis of several X-borne genes showed that both alleles are transcribed in a heterozygous female. Transcription of 14 BACs representing 19 X-borne genes was examined by RNA-FISH in female and male fibroblasts. An autosomal control gene was expressed from both alleles in nearly all nuclei, and four pseudoautosomal BACs were usually expressed from both alleles in male as well as female nuclei, showing that their Y loci are active. However, nine X-specific BACs were usually transcribed from only one allele. This suggests that while some genes on the platypus X are not dosage compensated, other genes do show some form of compensation via stochastic transcriptional inhibition, perhaps representing an ancestral system that evolved to be more tightly controlled in placental mammals such as human and mouse. PMID:18654631

  19. Importance of gene dosage in controlling dendritic arbor formation during development.

    PubMed

    Copf, Tijana

    2015-09-01

    Proper dendrite morphology is crucial for normal nervous system functioning. While a number of genes have been implicated in dendrite morphogenesis in both invertebrates and mammals, it remains unclear how developing dendrites respond to changes in gene dosage and what type of patterns their responses may follow. To understand this, I review here evidence from the recent literature, focusing on the genetic studies performed in the Drosophila larval dendritic arborization class IV neuron, an excellent cell type to understand dendrite morphogenesis. I summarize how class IV arbors change morphology in response to developmental fluctuations in the expression levels of 47 genes, studied by means of genetic manipulations such as loss-of-function and gain-of-function, and for which sufficient information is available. I find that arbors can respond to changing gene dosage in several distinct ways, each characterized by a singular dose-response curve. Interestingly, in 72% of cases arbors are sensitive, and thus adjust their morphology, in response to both decreases and increases in the expression of a given gene, indicating that dendrite morphogenesis is a process particularly sensitive to gene dosage. By summarizing the parallels between Drosophila and mammals, I show that many Drosophila dendrite morphogenesis genes have orthologs in mammals, and that some of these are associated with mammalian dendrite outgrowth and human neurodevelopmental disorders. One notable disease-related molecule is kinase Dyrk1A, thought to be a causative factor in Down syndrome. Both increases and decreases in Dyrk1A gene dosage lead to impaired dendrite morphogenesis, which may contribute to Down syndrome pathoetiology.

  20. Materials for Pharmaceutical Dosage Forms: Molecular Pharmaceutics and Controlled Release Drug Delivery Aspects

    PubMed Central

    Mansour, Heidi M.; Sohn, MinJi; Al-Ghananeem, Abeer; DeLuca, Patrick P.

    2010-01-01

    Controlled release delivery is available for many routes of administration and offers many advantages (as microparticles and nanoparticles) over immediate release delivery. These advantages include reduced dosing frequency, better therapeutic control, fewer side effects, and, consequently, these dosage forms are well accepted by patients. Advances in polymer material science, particle engineering design, manufacture, and nanotechnology have led the way to the introduction of several marketed controlled release products and several more are in pre-clinical and clinical development. PMID:20957095

  1. The Effects of Varying Chromosome Arm Dosage on Maize Plant Morphogenesis

    PubMed Central

    Brunelle, Dale C.; Sheridan, William F.

    2014-01-01

    Maize is an especially well-suited species for studying the effects of aneuploidy on plant development. We used B-A translocations and testers that were crossed seven times into inbred W22 to generate a dosage series for 14 chromosome arms. This is the first report of dosage effects on maize morphogenesis using inbred B-A stocks and inbred tester stocks. We compared plants containing one dose or three doses of each of the 14 chromosome arms with plants containing two doses for seven measured traits. These were leaf width, leaf length, plant height, ear height, internode length, ear node circumference, and tassel branch number. We observed the typical maize aneuploid syndrome wherein one dose was more widespread and more severe in its effects than three doses. All but two of the one-dose effects were negative, and all of the three-dose effects were negative. The occurrence of positive responses by hyperploid plants in our earlier B-A-A study and the absence of any positive responses among the hyperploids reported for the 14 simple B-A translocations tested for dosage effects in the present study and previously may reflect gene dosage interaction between the two chromosome arm segments present in the B-A-A translocations. The overall congruence of our results with those of previous studies suggests that the traits measured are quantitative traits controlled by multiple genes whose activities provide a balanced regulation that transcends individual inbred lines or diverse genetic backgrounds and that such genes may be especially abundant in chromosome arm 1L. PMID:24970866

  2. Magnetic marker monitoring: high resolution real-time tracking of oral solid dosage forms in the gastrointestinal tract.

    PubMed

    Weitschies, Werner; Blume, Henning; Mönnikes, Hubert

    2010-01-01

    Knowledge about the performance of dosage forms in the gastrointestinal tract is essential for the development of new oral delivery systems, as well as for the choice of the optimal formulation technology. Magnetic Marker Monitoring (MMM) is an imaging technology for the investigation of the behaviour of solid oral dosage forms within the gastrointestinal tract, which is based on the labelling of solid dosage forms as a magnetic dipole and determination of the location, orientation and strength of the dipole after oral administration using measurement equipment and localization methods that are established in biomagnetism. MMM enables the investigation of the performance of solid dosage forms in the gastrointestinal tract with a temporal resolution in the range of a few milliseconds and a spatial resolution in 3D in the range of some millimetres. Thereby, MMM provides real-time tracking of dosage forms in the gastrointestinal tract. MMM is also suitable for the determination of dosage form disintegration and for quantitative measurement of in vivo drug release in case of appropriate extended release dosage forms like hydrogel-forming matrix tablets. The combination of MMM with pharmacokinetic measurements (pharmacomagnetography) enables the determination of in vitro-in vivo correlations (IVIC) and the delineation of absorption sites in the gastrointestinal tract.

  3. Simultaneous determination of Fluticasone propionate and Azelastine hydrochloride in the presence of pharmaceutical dosage form additives.

    PubMed

    Merey, Hanan A; El-Mosallamy, Sally S; Hassan, Nagiba Y; El-Zeany, Badr A

    2016-05-05

    Fluticasone propionate (FLU) and Azelastine hydrochloride (AZE) are co-formulated with phenylethyl alcohol (PEA) and Benzalkonium chloride (BENZ) (as preservatives) in pharmaceutical dosage form for treatment of seasonal allergies. Different spectrophotometric methods were used for the simultaneous determination of cited drugs in the dosage form. Direct spectrophotometric method was used for determining of AZE, while Derivative of double divisor of ratio spectra (DD-RS), Ratio subtraction coupled with ratio difference method (RS-RD) and Mean centering of the ratio spectra (MCR) are used for the determination of FLU. The linearity of the proposed methods was investigated in the range of 5.00-40.00 and 5.00-80.00μg/mL for FLU and AZE, respectively. The specificity of the developed methods was investigated by analyzing laboratory prepared mixtures containing different ratios of cited drugs in addition to PEA and their pharmaceutical dosage form. The validity of the proposed methods was assessed using the standard addition technique. The obtained results were statistically compared with those obtained by official or the reported method for FLU or AZE, respectively showing no significant difference with respect to accuracy and precision at p=0.05.

  4. Rapid optimization of gene dosage in E. coli using DIAL strains

    PubMed Central

    2011-01-01

    Background Engineers frequently vary design parameters to optimize the behaviour of a system. However, synthetic biologists lack the tools to rapidly explore a critical design parameter, gene expression level, and have no means of systematically varying the dosage of an entire genetic circuit. As a step toward overcoming this shortfall, we have developed a technology that enables the same plasmid to be maintained at different copy numbers in a set of closely related cells. This provides a rapid method for exploring gene or cassette dosage effects. Results We engineered two sets of strains to constitutively provide a trans-acting replication factor, either Pi of the R6K plasmid or RepA of the ColE2 plasmid, at different doses. Each DIAL (different allele) strain supports the replication of a corresponding plasmid at a constant level between 1 and 250 copies per cell. The plasmids exhibit cell-to-cell variability comparable to other popular replicons, but with improved stability. Since the origins are orthogonal, both replication factors can be incorporated into the same cell. We demonstrate the utility of these strains by rapidly assessing the optimal expression level of a model biosynthetic pathway for violecein. Conclusions The DIAL strains can rapidly optimize single gene expression levels, help balance expression of functionally coupled genetic elements, improve investigation of gene and circuit dosage effects, and enable faster development of metabolic pathways. PMID:21787416

  5. Development and in vitro evaluation of expandable gastroretentive dosage forms based on compressed collagen sponges.

    PubMed

    Gröning, R; Cloer, C; Müller, R S

    2006-07-01

    The objective of this study was to develop and evaluate new collagen gastroretentive dosage forms (GRDFs) which expand in the stomach after contact with gastric fluids. The GRDFs should remain in the stomach for a prolonged period of time due to their size. The dosage forms were prepared from collagen sponges. The sponges were manufactured by freeze-drying a riboflavin-containing collagen solution. A computer controlled material supply was constructed to transport precompressed collagen into a tablet machine. A second type of tablet was manufactured by combining compressed collagen sponges with hydrophilic matrix layers of hydroxypropylmethylcellulose. Matrix layers containing captopril or aciclovir were developed. In vitro experiments were performed with both types of dosage forms. The collagen tablets expand within a few minutes after contact with artificial gastric juice and form a drug delivery system with a size of 8 mm x 18 mm x 60 mm. Riboflavin is released over 16 h. If two layer tablets are used, the release of aciclovir or captopril can be controlled by the composition of the sustained release layer.

  6. Barrier coated drug layered particles for enhanced performance of amorphous solid dispersion dosage form.

    PubMed

    Puri, Vibha; Dantuluri, Ajay K; Bansal, Arvind K

    2012-01-01

    Amorphous solid dispersions (ASDs) may entail tailor-made dosage form design to exploit their solubility advantage. Surface phenomena dominated the performance of amorphous celecoxib solid dispersion (ACSD) comprising of amorphous celecoxib (A-CLB), polyvinylpyrrolidone, and meglumine (7:2:1, w/w). ACSD cohesive interfacial interactions hindered its capsule dosage form dissolution (Puri V, Dhantuluri AK, Bansal AK 2011. J Pharm Sci 100:2460-2468). Furthermore, ACSD underwent significant devitrification under environmental stress. In the present study, enthalpy relaxation studies revealed its free surface to contribute to molecular mobility. Based on all these observations, barrier coated amorphous CLB solid dispersion layered particles (ADLP) were developed by Wurster process, using microcrystalline cellulose as substrate and polyvinyl alcohol (PVA), inulin, and polyvinyl acetate phthalate (PVAP) as coating excipients. Capsule formulations of barrier coated-ADLP could achieve rapid dispersibility and high drug release. Evaluation under varying temperature and RH conditions suggested the crystallization inhibitory efficiency in order of inulin < PVA ≈ PVAP; however, under only temperature treatment, crystallization inhibition increased with increase in T(g) of the coating material. Simulated studies using DSC evidenced drug-polymer mixing at the interface as a potential mechanism for surface stabilization. In conclusion, surface modification yielded a fast dispersing robust high drug load ASD based dosage form.

  7. Simultaneous determination of Fluticasone propionate and Azelastine hydrochloride in the presence of pharmaceutical dosage form additives

    NASA Astrophysics Data System (ADS)

    Merey, Hanan A.; El-Mosallamy, Sally S.; Hassan, Nagiba Y.; El-Zeany, Badr A.

    2016-05-01

    Fluticasone propionate (FLU) and Azelastine hydrochloride (AZE) are co-formulated with phenylethyl alcohol (PEA) and Benzalkonium chloride (BENZ) (as preservatives) in pharmaceutical dosage form for treatment of seasonal allergies. Different spectrophotometric methods were used for the simultaneous determination of cited drugs in the dosage form. Direct spectrophotometric method was used for determining of AZE, while Derivative of double divisor of ratio spectra (DD-RS), Ratio subtraction coupled with ratio difference method (RS-RD) and Mean centering of the ratio spectra (MCR) are used for the determination of FLU. The linearity of the proposed methods was investigated in the range of 5.00-40.00 and 5.00-80.00 μg/mL for FLU and AZE, respectively. The specificity of the developed methods was investigated by analyzing laboratory prepared mixtures containing different ratios of cited drugs in addition to PEA and their pharmaceutical dosage form. The validity of the proposed methods was assessed using the standard addition technique. The obtained results were statistically compared with those obtained by official or the reported method for FLU or AZE, respectively showing no significant difference with respect to accuracy and precision at p = 0.05.

  8. Absorbance correction method for estimation of telmisartan and metoprolol succinate in combined tablet dosage forms

    PubMed Central

    Patel, Komal; Patel, Amit; Dave, Jayant; Patel, Chaganbhai

    2012-01-01

    Aim and Background: The present manuscript describes simple, sensitive, rapid, accurate, precise and economical spectrophotometric method for the simultaneous determination of telmisartan and metoprolol succinate in combined tablet dosage form. Materials and Methods: The method is based on the absorbance correction equations for analysis of both the drugs using methanol as solvent. Telmisartan has absorbance maxima at 296 nm and metoprolol succinate has absorbance maxima at 223 nm in methanol. The linearity was obtained in the concentration range of 2-16 μg/ ml and 3-24 μg/ml for telmisartan and metoprolol succinate, respectively. The concentrations of the drugs were determined by using absorbance correction method at both the wavelengths. The method was successfully applied to pharmaceutical dosage form because no interference from the tablet excipients was found. The suitability of this method for the quantitative determination of telmisartan and metoprolol succinate was proved by validation. The proposed method was found to be simple and sensitive for the quality control application of telmisartan and metoprolol succinate in pharmaceutical dosage form. Result: The result of analysis has been validated statistically and by recovery studies. Recoveries were found in the range of 98.08-100.55% of telmisartan and 98.41-101.87% of metoprolol succinate. PMID:23781489

  9. Development of Oromucosal Dosage Forms by Combining Electrospinning and Inkjet Printing.

    PubMed

    Palo, Mirja; Kogermann, Karin; Laidmäe, Ivo; Meos, Andres; Preis, Maren; Heinämäki, Jyrki; Sandler, Niklas

    2017-03-06

    Printing technology has been shown to enable flexible fabrication of solid dosage forms for personalized drug therapy. Several methods can be applied for tailoring the properties of the printed pharmaceuticals. In this study, the use of electrospun fibrous substrates in the fabrication of inkjet-printed dosage forms was investigated. A single-drug formulation with lidocaine hydrochloride (LH) and a combination drug system containing LH and piroxicam (PRX) for oromucosal administration were prepared. The LH was deposited on the electrospun and cross-linked gelatin substrates by inkjet printing, whereas PRX was incorporated within the substrate fibers during electrospinning. The solid state analysis of the electrospun substrates showed that PRX was in an amorphous state within the fibers. Furthermore, the results indicated the entrapment and solidification of the dissolved LH within the fibrous gelatin matrix. The printed drug amount (2-3 mg) was in good correlation with the theoretical dose calculated based on the printing parameters. However, a noticeable degradation of the printed LH was detected after a few months. An immediate release (over 85% drug release after 8 min) of both drugs from the printed dosage forms was observed. In conclusion, the prepared electrospun gelatin scaffolds were shown to be suitable substrates for inkjet printing of oromucosal formulations. The combination of electrospinning and inkjet printing allowed the preparation of a dual drug system.

  10. Influence of dosage, consciousness, and nifedipine on the acute pressor response to intraperitoneally administered cadmium. [Rats

    SciTech Connect

    Hall, C.E.; Hungerford, S.

    1982-05-01

    The acute pressor effect of intraperitoneally administered cadmium was explored over the dose range 0.015-2 mg/kg in both pentobarbital-anesthetized and conscious rats. The former first respondent at 0.031 mg/kg, and successive doublings of that dosage increased the highest pressures attained in a stepwise fashion until a dosage of 0.25 mg/kg, the maximally effective quantity, was reached. Arterial pressure did not rise in conscious rats until a dose of 1 mg/kg, which gave the maximum response within the range examined. Heart-rate changes with Cd were slight, and rarely significant at a given dosage, but pentobarbital invariably caused tachycardia. Anesthetized rats thus gave a graded response, while conscious animals reacted in an all-or-none fashion. The increased pressor responsiveness of rats under pentobarbital can not be ascribed to its cardiac parasympatholytic effects, since sensitivity was not conferred upon conscious rats when pretreated with atropine at a dose producing even greater tachycardia than that caused by pentobarbital. Nifedipine, which blocks calcium entry into smooth muscle cells, prevented the pressor response to cadmium when given as pretreatment and terminated an ongoing response when give intercurrently. Possible mechanisms to account for the observed behavior are considered.

  11. The Drosophila over compensating males gene genetically inhibits dosage compensation in males.

    PubMed

    Lim, Chiat Koo; Kelley, Richard L

    2013-01-01

    Male Drosophila are monosomic for the X chromosome, but survive due to dosage compensation. They use the Male Specific Lethal (MSL) complex composed of noncoding roX RNA and histone modifying enzymes to hypertranscribe most genes along the X ∼1.6-1.8 fold relative to each female allele. It is not known how the MSL complex achieves this precise adjustment to a large and diverse set of target genes. We carried out a genetic screen searching for novel factors that regulate dosage compensation in flies. This strategy generated thirty alleles in a previously uncharacterized gene, over compensating males (ocm) that antagonizes some aspect of MSL activity. The mutations were initially recovered because they derepressed an MSL-dependent eye color reporter. Null ocm mutations are lethal to both sexes early in development revealing an essential function. Combinations of hypomorphic ocm alleles display a male specific lethality similar to mutations in the classic msl genes, but ocm males die due to excessive, rather than lack of dosage compensation. Males that die due to very low MSL activity can be partially rescued by ocm mutations. Likewise, males that would die from ocm mutations can be rescued by reducing the dose of various msl and roX genes. ocm encodes a large nuclear protein that shares a novel cysteine rich motif with known transcription factors.

  12. Concerted copy number variation balances ribosomal DNA dosage in human and mouse genomes

    PubMed Central

    Gibbons, John G.; Branco, Alan T.; Godinho, Susana A.; Yu, Shoukai; Lemos, Bernardo

    2015-01-01

    Tandemly repeated ribosomal DNA (rDNA) arrays are among the most evolutionary dynamic loci of eukaryotic genomes. The loci code for essential cellular components, yet exhibit extensive copy number (CN) variation within and between species. CN might be partly determined by the requirement of dosage balance between the 5S and 45S rDNA arrays. The arrays are nonhomologous, physically unlinked in mammals, and encode functionally interdependent RNA components of the ribosome. Here we show that the 5S and 45S rDNA arrays exhibit concerted CN variation (cCNV). Despite 5S and 45S rDNA elements residing on different chromosomes and lacking sequence similarity, cCNV between these loci is strong, evolutionarily conserved in humans and mice, and manifested across individual genotypes in natural populations and pedigrees. Finally, we observe that bisphenol A induces rapid and parallel modulation of 5S and 45S rDNA CN. Our observations reveal a novel mode of genome variation, indicate that natural selection contributed to the evolution and conservation of cCNV, and support the hypothesis that 5S CN is partly determined by the requirement of dosage balance with the 45S rDNA array. We suggest that human disease variation might be traced to disrupted rDNA dosage balance in the genome. PMID:25583482

  13. Computer-aided dosage in oral anticoagulation therapy using phenprocoumon. Problems and approaches.

    PubMed

    Cromme, L; Völler, H; Gäbler, F; Salzwedel, A; Taborski, U

    2010-11-01

    Oral anticoagulation using vitamin K antagonists has been established for over 50 years. Although it is highly effective in preventing thromboembolic incidents, its therapeutic control still remains problematic. Therefore, a computer-aided approach is recommended for deriving dosages. Up to now, the dosage is often based on the visual inspection of previous INR measurements, average weekly doses, and the INR target range. Statistical variations of measurement results and time-delayed effects of dosages, however, frequently result in the misinterpretation of data and suggest pseudo-trends. Treating physicians are not only responsible for determining the patient-specific maintenance dose, but must also respond to deviating INR values, overdosage or underdosage, initiate the oral anticoagulation therapy, and control the INR level in case of a new target range (bridging). Instructive examples are provided to illustrate the described difficulties. A computer-aided expert system is currently developed to ensure the therapeutic safety under the specified conditions. We present preliminary results from a study designed to validate mathematical models underlying such expert systems.

  14. Contraceptive Use Affects Overall Olfactory Performance: Investigation of Estradiol Dosage and Duration of Intake

    PubMed Central

    Ohrenberger, Iris

    2016-01-01

    The influence of female sex steroids on cognitive performance and sensory perception has been investigated for decades. However, previous research that studied olfaction revealed inconsistent results. The main aim of this study was to investigate the effects of different ethinyl estradiol (EE) concentrations of oral contraceptives and duration of intake on olfactory function. Forty-two healthy women, with regular intake of either high or low EE dosage over at least one year and up to 15 years participated in this study. Results revealed a significant concordance between a priori categorization in the two groups with high and low EE dosage and data-driven hierarchical clustering (p = 0.008). Furthermore, significantly higher olfactory performance was observed in women using low-dose products compared to women using high-dosed products (p = 0.019). These findings indicate different effects of pill use with regard to EE concentration. We therefore strongly recommend the acquisition of information about EE dosage of oral contraceptives to reduce potential confounding factors when investigating sensory systems. PMID:28002464

  15. Influence of the dosage of super plasticizer on properties of high performance concrete

    NASA Astrophysics Data System (ADS)

    Baroninsh, J.; Lagzdina, S.; Krage, L.; Shahmenko, G.

    2011-12-01

    High-performance concrete (HPC) is defined as concrete that meets special combinations of performance and uniformity requirements. That cannot always be achieved routinely using conventional constituents and ordinary mixing, placing, and curing practices. The objective of this study is to provide some experimental data that can be useful in engineering practice for producing HPC using conventional constituents and ordinary mixing and curing practices using less expensive raw materials. In the given study, the influence of the polycarboxylates based super plasticizer (SP) (high-range water reducer) at different dosages to the properties of HPC was investigated. SP in concrete mixtures was added with ratios of 1.0%, 1.5%, and 2.5% by weight of cement. The samples characteristics of produced concrete were compared with each other. Performance of the concrete mixes was determined for fresh and hardened concrete, which included cone test, compressive strength and porosity measurements. Obtained results indicated that increasing dosage of SP to 2.5% by weight of cement improved the performance of concrete and contributed more to the improvement of its transportability properties as well as mechanical properties, but at the same time has considerably reduced water/cement (W/C) ratio. Porosity tests of hardened concrete showed influence of SP dosage to the volume of pores accessible to water.

  16. Selection of solid dosage form composition through drug-excipient compatibility testing.

    PubMed

    Serajuddin, A T; Thakur, A B; Ghoshal, R N; Fakes, M G; Ranadive, S A; Morris, K R; Varia, S A

    1999-07-01

    A drug-excipient compatibility screening model was developed by which potential stability problems due to interactions of drug substances with excipients in solid dosage forms can be predicted. The model involved storing drug-excipient blends with 20% added water in closed glass vials at 50 degrees C and analyzing them after 1 and 3 weeks for chemical and physical stability. The total weight of drug-excipient blend in a vial was usually kept at about 200 mg. The amount of drug substance in a blend was determined on the basis of the expected drug-to-excipient ratio in the final formulation. Potential roles of several key factors, such as the chemical nature of the excipient, drug-to-excipient ratio, moisture, microenvironmental pH of the drug-excipient mixture, temperature, and light, on dosage form stability could be identified by using the model. Certain physical changes, such as polymorphic conversion or change from crystalline to amorphous form, that could occur in drug-excipient mixtures were also studied. Selection of dosage form composition by using this model at the outset of a drug development program would lead to reduction of "surprise" problems during long-term stability testing of drug products.

  17. Disaggregating polyploidy, parental genome dosage and hybridity contributions to heterosis in Arabidopsis thaliana.

    PubMed

    Fort, Antoine; Ryder, Peter; McKeown, Peter C; Wijnen, Cris; Aarts, Mark G; Sulpice, Ronan; Spillane, Charles

    2016-01-01

    Heterosis is the phenomenon whereby hybrid offspring of genetically divergent parents display superior characteristics compared with their parents. Although hybridity and polyploidy can influence heterosis in hybrid plants, the differential contributions of hybridity vs polyploidy to heterosis effects remain unknown. To address this question, we investigated heterosis effects on rosette size and growth rate of 88 distinct F1 lines of Arabidopsis thaliana consisting of diploids, reciprocal triploids and tetraploids in isogenic and hybrid genetic contexts. 'Heterosis without hybridity' effects on plant size can be generated in genetically isogenic F1 triploid plants. Paternal genome excess F1 triploids display positive heterosis, whereas maternal genome excess F1 s display negative heterosis effects. Paternal genome dosage increases plant size in F1 hybrid triploid plants by, on average, 57% (in contrast with 35% increase displayed by F1 diploid hybrids). Such effects probably derive from differential seed size, as the growth rate of triploids was similar to diploids. Tetraploid plants display a lower growth rate compared with other ploidies, whereas hybrids display increased early stage growth rate. By disaggregating heterosis effects caused by hybridity vs genome dosage, we advance our understanding of heterosis in plants and facilitate novel paternal genome dosage-based strategies to enhance heterosis effects in crop plants.

  18. Long-term treatment with high-dosage bromocriptine in advanced Parkinson's disease.

    PubMed

    Jansen, E N; Meerwaldt, J D

    1987-01-01

    Long-term follow-up indicated that levodopa as a replacement therapy merely improves the parkinsonian symptoms, and does so for only a limited number of years. The reason for this tachyphylaxis or declining efficacy in levodopa therapy and the increasing number and intensity of various distressing difficulties in the management of Parkinson's disease, such as dyskinesias and on-off phenomena, is the main subject of many recent studies. It is still widely accepted that levodopa provides the best therapeutic tool for Parkinson's disease. Bromocriptine, an ergot derivative, is the main clinically used dopamine agonist, and it has been established as a valuable adjunct in the treatment of Parkinson's disease. Bromocriptine is most useful in patients with a declining efficacy of levodopa treatment, in patients with diurnal oscillations in motor performance, especially in patients with wearing-off phenomena, and in patients with onset and end-of-dose dyskinesias. The question of bromocriptine dosage, required to obtain an optimal benefit and a decreased rate of late adverse reactions, is quite controversial. The trend has been to lower daily dosage of bromocriptine, i.e., low doses suffice in patients with mild, early disease. Higher doses of bromocriptine seem to be required in patients with severe parkinsonian deficits. In this retrospective study of 8 years experience with high dosage of bromocriptine in levodopa response-losing parkinsonian patients, the adjunction of bromocriptine had a clear-cut but short-lasting beneficial effect on the disability scores.(ABSTRACT TRUNCATED AT 250 WORDS)

  19. Arsenic removal from groundwater using iron electrocoagulation: effect of charge dosage rate.

    PubMed

    Amrose, Susan; Gadgil, Ashok; Srinivasan, Venkat; Kowolik, Kristin; Muller, Marc; Huang, Jessica; Kostecki, Robert

    2013-01-01

    We demonstrate that electrocoagulation (EC) using iron electrodes can reduce arsenic below 10 μg/L in synthetic Bangladesh groundwater and in real groundwater from Bangladesh and Cambodia, while investigating the effect of operating parameters that are often overlooked, such as charge dosage rate. We measure arsenic removal performance over a larger range of current density than in any other single previous EC study (5000-fold: 0.02 - 100 mA/cm(2)) and over a wide range of charge dosage rates (0.060 - 18 Coulombs/L/min). We find that charge dosage rate has significant effects on both removal capacity (μg-As removed/Coulomb) and treatment time and is the appropriate parameter to maintain performance when scaling to different active areas and volumes. We estimate the operating costs of EC treatment in Bangladesh groundwater to be $0.22/m(3). Waste sludge (~80 - 120 mg/L), when tested with the Toxic Characteristic Leachate Protocol (TCLP), is characterized as non-hazardous. Although our focus is on developing a practical device, our results suggest that As[III] is mostly oxidized via a chemical pathway and does not rely on processes occurring at the anode. Supplementary materials are available for this article. Go to the publisher's online edition of Journal of Environmental Science and Health, Part A, to view the free supplemental file.

  20. Applications of Polymers as Pharmaceutical Excipients in Solid Oral Dosage Forms.

    PubMed

    Debotton, Nir; Dahan, Arik

    2017-01-01

    Over the last few decades, polymers have been extensively used as pharmaceutical excipients in drug delivery systems. Pharmaceutical polymers evolved from being simply used as gelatin shells comprising capsule to offering great formulation advantages including enabling controlled/slow release and specific targeting of drugs to the site(s) of action (the "magic bullets" concept), hence hold a significant clinical promise. Oral administration of solid dosage forms (e.g., tablets and capsules) is the most common and convenient route of drug administration. When formulating challenging molecules into solid oral dosage forms, polymeric pharmaceutical excipients permit masking undesired physicochemical properties of drugs and consequently, altering their pharmacokinetic profiles to improve the therapeutic effect. As a result, the number of synthetic and natural polymers available commercially as pharmaceutical excipients has increased dramatically, offering potential solutions to various difficulties. For instance, the different polymers may allow increased solubility, swellability, viscosity, biodegradability, advanced coatings, pH dependency, mucodhesion, and inhibition of crystallization. The aim of this article is to provide a wide angle prospect of the different uses of pharmaceutical polymers in solid oral dosage forms. The various types of polymeric excipients are presented, and their distinctive role in oral drug delivery is emphasized. The comprehensive know-how provided in this article may allow scientists to use these polymeric excipients rationally, to fully exploit their different features and potential influence on drug delivery, with the overall aim of making better drug products.

  1. Biowaiver monographs for immediate release solid oral dosage forms: ethambutol dihydrochloride.

    PubMed

    Becker, C; Dressman, J B; Amidon, G L; Junginger, H E; Kopp, S; Midha, K K; Shah, V P; Stavchansky, S; Barends, D M

    2008-04-01

    Literature data relevant to the decision to allow a waiver of in vivo bioequivalence (BE) testing for the approval of immediate release (IR) solid oral dosage forms containing ethambutol dihydrochloride as the only active pharmaceutical ingredient (API) are reviewed. Ethambutol dihydrochloride is a Biopharmaceutics Classification System (BCS) Class III drug with permeability properties approaching the border between BCS Class I and III. BE problems of ethambutol formulations containing different excipients and different dosages forms have not been reported and hence the risk of bioinequivalence caused by excipients is low. Ethambutol has a narrow therapeutic index related to ocular toxicity. However, as long as the prescribers' information of the test product stipulates the need for regular monitoring of ocular toxicity, the additional patient risk is deemed acceptable. It is concluded that a biowaiver can be recommended for IR solid oral dosage forms provided that the test product (a) contains only excipients present in ethambutol IR solid oral drug products approved in ICH or associated countries, for instance as presented in this paper, (b) complies with the criteria for "very rapidly dissolving" and (c) has a prescribers' information indicating the need for testing the patient's vision prior to initiating ethambutol therapy and regularly during therapy.

  2. Biowaiver monographs for immediate release solid oral dosage forms: diclofenac sodium and diclofenac potassium.

    PubMed

    Chuasuwan, B; Binjesoh, V; Polli, J E; Zhang, H; Amidon, G L; Junginger, H E; Midha, K K; Shah, V P; Stavchansky, S; Dressman, J B; Barends, D M

    2009-04-01

    Literature data are reviewed regarding the scientific advisability of allowing a waiver of in vivo bioequivalence (BE) testing for the approval of immediate release (IR) solid oral dosage forms containing either diclofenac potassium and diclofenac sodium. Within the biopharmaceutics classification system (BCS), diclofenac potassium and diclofenac sodium are each BCS class II active pharmaceutical ingredients (APIs). However, a biowaiver can be recommended for IR drug products of each salt form, due to their therapeutic use, therapeutic index, pharmacokinetic properties, potential for excipient interactions, and performance in reported BE/bioavailability (BA) studies, provided: (a) test and comparator contain the same diclofenac salt; (b) the dosage form of the test and comparator is identical; (c) the test product contains only excipients present in diclofenac drug products approved in ICH or associated countries in the same dosage form, for instance as presented in this paper; (d) test drug product and comparator dissolve 85% in 30 min or less in 900 mL buffer pH 6.8, using the paddle apparatus at 75 rpm or the basket apparatus at 100 rpm; and (e) test product and comparator show dissolution profile similarity in pH 1.2, 4.5, and 6.8.

  3. Dosage assessment of valnemulin in pigs based on population pharmacokinetic and Monte Carlo simulation.

    PubMed

    Yuan, L G; Tang, Y Z; Zhang, Y X; Sun, J; Luo, X Y; Zhu, L X; Zhang, Z; Wang, R; Liu, Y H

    2015-08-01

    To estimate the valnemulin pharmacokinetic profile in a swine population and to assess a dosage regimen for increasing the likelihood of optimization. This study was, respectively, performed in 22 sows culled by p.o. administration and in 80 growing-finishing pigs by i.v. administration at a single dose of 10 mg/kg to develop a population pharmacokinetic model and Monte Carlo simulation. The relationships among the plasma concentration, dose, and time of valnemulin in pigs were illustrated as C(i,v) = X(0 )(8.4191 × 10(-4) × e(-0.2371t) + 1.2788 × 10(-5) × e(-0.0069t)) after i.v. and C(p.o) = X(0) (-8.4964 × 10(-4) × e(-0.5840t) + 8.4195 × e(-0.2371t) + 7.6869 × 10(-6) × e(-0.0069t)) after p.o. Monte Carlo simulation showed that T(>MIC) was more than 24 h when a single daily dosage at 13.5 mg/kg BW in pigs was administrated by p.o., and MIC was 0.031 mg/L. It was concluded that the current dosage regimen at 10-12 mg/kg BW led to valnemulin underexposure if the MIC was more than 0.031 mg/L and could increase the risk of treatment failure and/or drug resistance.

  4. Topical cream-based dosage forms of the macrocyclic drug delivery vehicle cucurbit[6]uril.

    PubMed

    Seif, Marian; Impelido, Michael L; Apps, Michael G; Wheate, Nial J

    2014-01-01

    The macrocycle family of molecules called cucurbit[n]urils are potential drug delivery vehicles as they are able to form host-guest complexes with many different classes of drugs. This study aimed to examine the utility of Cucurbit[6]uril (CB[6]) in topical cream-based formulations for either localised treatment or for transdermal delivery. Cucurbit[6]uril was formulated into both buffered cream aqueous- and oily cream-based dosage forms. The solid state interaction of CB[6] with other excipients was studied by differential scanning calorimetry and the macrocycle's transdermal permeability was determined using rat skin. Significant solid state interactions were observed between CB[6] and the other dosage form excipients. At concentrations up to 32% w/w the buffered aqueous cream maintained its normal consistency and could be effectively applied to skin, but the oily cream was too stiff and is not suitable as a dosage form. Cucurbit[6]uril does not permeate through skin; as such, the results imply that cucurbituril-based topical creams may potentially only have applications for localised skin treatment and not for transdermal drug delivery.

  5. Dropwise additive manufacturing of pharmaceutical products for solvent-based dosage forms.

    PubMed

    Hirshfield, Laura; Giridhar, Arun; Taylor, Lynne S; Harris, Michael T; Reklaitis, Gintaras V

    2014-02-01

    In recent years, the US Food and Drug Administration has encouraged pharmaceutical companies to develop more innovative and efficient manufacturing methods with improved online monitoring and control. Mini-manufacturing of medicine is one such method enabling the creation of individualized product forms for each patient. This work presents dropwise additive manufacturing of pharmaceutical products (DAMPP), an automated, controlled mini-manufacturing method that deposits active pharmaceutical ingredients (APIs) directly onto edible substrates using drop-on-demand (DoD) inkjet printing technology. The use of DoD technology allows for precise control over the material properties, drug solid state form, drop size, and drop dynamics and can be beneficial in the creation of high-potency drug forms, combination drugs with multiple APIs or individualized medicine products tailored to a specific patient. In this work, DAMPP was used to create dosage forms from solvent-based formulations consisting of API, polymer, and solvent carrier. The forms were then analyzed to determine the reproducibility of creating an on-target dosage form, the morphology of the API of the final form and the dissolution behavior of the drug over time. DAMPP is found to be a viable alternative to traditional mass-manufacturing methods for solvent-based oral dosage forms.

  6. Hyperspectral imaging in quality control of inkjet printed personalised dosage forms.

    PubMed

    Vakili, Hossein; Kolakovic, Ruzica; Genina, Natalja; Marmion, Mathieu; Salo, Harri; Ihalainen, Petri; Peltonen, Jouko; Sandler, Niklas

    2015-04-10

    The aim of the study was to investigate applicability of near infra-red (NIR) hyperspectral imaging technique in quality control of printed personalised dosage forms. Inkjet printing technology was utilized to fabricate escalating doses of an active pharmaceutical ingredient (API). A solution containing anhydrous theophylline as the model drug was developed as a printable formulation. Single units solid dosage forms (SDFs) were prepared by jetting the solution onto 1 cm × 1 cm areas on carrier substrate with multiple printing passes. It was found that the number of printing passes was in excellent correlation (R(2)=0.9994) with the amount of the dispensed drug (μg cm(-2)) based on the UV calibration plot. The API dose escalation was approximately 7.5 μg cm(-2) for each printing pass concluding that inkjet printing technology can optimally provide solutions to accurate deposition of active substances with a potential for personalized dosing. Principal component analysis (PCA) was carried out in order to visualize the trends in the hyperspectral data. Subsequently, a quantitative partial least squares (PLS) regression model was created. NIR hyperspectral imaging proved (R(2)=0.9767) to be a reliable, rapid and non-destructive method to optimize quality control of these planar printed dosage forms.

  7. Biowaiver monographs for immediate-release solid oral dosage forms: stavudine.

    PubMed

    Silva, Arthur L L; Cristofoletti, Rodrigo; Storpirtis, Silvia; Sousa, Varley D; Junginger, Hans E; Shah, Vinod P; Stavchansky, Salomon; Dressman, Jennifer B; Barends, Dirk M

    2012-01-01

    Literature data relevant to the decision to allow a waiver of in vivo bioequivalence (BE) testing for the approval of immediate-release (IR) solid oral dosage forms containing stavudine (d4T) are reviewed. According to Biopharmaceutics Classification System (BCS), d4T can be assigned to BCS class I. No problems with BE of IR d4T formulations containing different excipients and produced by different manufacturing methods have been reported and, hence, the risk of bioinequivalence caused by these factors appears to be low. Furthermore, d4T has a wide therapeutic index. It is concluded that a biowaiver is appropriate for IR solid oral dosage forms containing d4T as the single active pharmaceutical ingredient (API) provided that (a) the test product contains only excipients present in the IR d4T drug products that have been approved in a number of countries for the same dosage form, and (b) both test product and its comparator are either "very rapidly dissolving" or "rapidly dissolving" with similarity of dissolution profiles demonstrated at pH 1.2, 4.5, and 6.8.

  8. Current status of amorphous formulation and other special dosage forms as formulations for early clinical phases.

    PubMed

    Kawakami, Kohsaku

    2009-09-01

    Although most chemists in the pharmaceutical industry have a good understanding on favorable physicochemical properties for drug candidates, formulators must still deal with many challenging candidates. On the other hand, formulators are not allowed to spend much time on formulation development for early phases of the clinical studies. Thus, it is basically difficult to apply special dosage form technologies to the candidates for the first-in-human formulations. Despite the availability of numerous reviews on oral special dosage forms, information on their applicability as the early phase formulation has been limited. This article describes quick review on the oral special dosage forms that may be applied to the early clinical formulations, followed by discussion focused on the amorphous formulations, which still has relatively many issues to be proved for the general use. The major problems that inhibit the use of the amorphous formulation are difficulty in the manufacturing and the poor chemical/physical stability. Notably, the poor physical stability can be critical, because of not the poor stability itself but the difficulty in the timely evaluation in the preclinical developmental timeframes. Research directions of the amorphous formulations are suggested to utilize this promising technology without disturbing the preclinical developmental timelines.

  9. Assessment of X Chromosome Dosage Compensation in Caenorhabditis elegans by Phenotypic Analysis of lin-14

    PubMed Central

    DeLong, Leslie; Casson, Lawrence P.; Meyer, Barbara J.

    1987-01-01

    Caenorhabditis elegans compensates for the difference in X chromosome gene dose between males (XO) and hermaphrodites (XX) through a mechanism that equalizes the levels of X-specific mRNA transcripts between the two sexes. We have devised a sensitive and quantitative genetic assay to measure perturbations in X chromosome gene expression caused by mutations that affect this process of dosage compensation. The assay is based on quantitating the precocious alae phenotype caused by a mutation that reduces but does not eliminate the function of the X-linked gene lin-14. We demonstrate that in diploid animals the lin-14 gene is dosage compensated between XO and XX animals. In XXX diploid animals, however, lin-14 expression is not compensated, implying that the normal dosage compensation mechanism in C. elegans lacks the capacity to compensate completely for the additional X chromosome in triplo-X animals. Using the lin-14 assay we compare the effects of mutations in the genes dpy-21, dpy-26, dpy-27, dpy-28, and dpy-22 on X-linked gene expression. Additionally, in the case of dpy-21 we correlate the change in phenotypic expression of lin-14 with a corresponding change in the lin-14 mRNA transcript level. PMID:3428573

  10. Individual Oral Therapy with Immediate Release and Effervescent Formulations Delivered by the Solid Dosage Pen

    PubMed Central

    Wening, Klaus; Laukamp, Eva Julia; Thommes, Markus; Breitkreutz, Jörg

    2012-01-01

    New devices enabling freely selectable dosing of solid oral medications are urgently needed for personalized medicine. One approach is the use of the recently published Solid Dosage Pen, allowing flexible dosing of tablet-like sustained release slices from drug loaded extruded strands. Slices were suitable for oral single dosed application. The aim of the present study was the development of immediate release dosage forms for applications of the device, especially for young children. Using two model drugs, two different concepts were investigated and evaluated. Effervescent formulations were manufactured by an organic wet-extrusion process and immediate release formulations by a melt-extrusion process. Dissolution experiments were performed for both formulations to ensure the immediate release behavior. Extruded strands were individually dosed by the Solid Dosage Pen. Various doses of the two formulations were analyzed regarding uniformity of mass and content according to pharmacopoeial specifications. Proof of concept was demonstrated in both approaches as results comply with the regulatory requirements. Furthermore, storing stress tests were performed and drug formulations were characterized after storing. The results show that suitable packaging material has been selected and storage stability is probable. PMID:25562361

  11. The Influence of Ethnicity on Warfarin Dosage Requirements in the Chilean Population

    PubMed Central

    Subiabre, Valeska; Palomo, Ivan; Guzmán, Neftalí; Retamales, Eduardo; Henríquez, Hugo; Gonzalez, Luis

    2015-01-01

    Background Vitamin K antagonists are drugs that are widely prescribed around the world and their use has helped improve the prognosis of patients with thromboembolic disease. However, a high interindividual variability has been observed in dosage requirements to reach the desired anticoagulation range that could be due to environmental and genetic factors. Studies suggest that ethnicity influences coumarin response, supporting the observed differences in dose requirements across various populations. Studies using mitochondrial DNA (mtDNA) markers have suggested that the Chilean population has a predominantly Amerindian genetic pool. Objective To evaluate the influence of ethnicity, defined by the presence of Amerindian mtDNA haplogroups, on the variability in therapeutic response to warfarin in the Chilean population. Methods A total of 191 patients treated with warfarin were included in this study. Analysis of the mitochondrial genome for detecting the presence of Amerindian mtDNA haplogroups was performed using polymerase chain reaction and polymerase chain reaction restriction fragment length polymorphism techniques. The evaluation of warfarin requirements according to each haplogroup was performed by ANOVA with a 95% CI and assuming statistical significance at P < 0.05. Results Based on the presence of an mtDNA haplogroup, 91% of the Chilean population had an Amerindian background. There were no significant differences in warfarin dosage requirements among the different Amerindian haplogroups (P = 0.083). Conclusions The presence of Amerindian mtDNA haplogroup does not influence warfarin dosage requirements in the Chilean population. PMID:25709720

  12. Position Effect Variegation and Viability Are Both Sensitive to Dosage of Constitutive Heterochromatin in Drosophila

    PubMed Central

    Berloco, Maria; Palumbo, Gioacchino; Piacentini, Lucia; Pimpinelli, Sergio; Fanti, Laura

    2014-01-01

    The dosage effect of Y-chromosome heterochromatin on suppression of position effect variegation (PEV) has long been well-known in Drosophila. The phenotypic effects of increasing the overall dosage of Y heterochromatin have also been demonstrated; hyperploidy of the Y chromosome produces male sterility and many somatic defects including variegation and abnormal legs and wings. This work addresses whether the suppression of position effect variegation (PEV) is a general feature of the heterochromatin (independent of the chromosome of origin) and whether a hyperdosage of heterochromatin can affect viability. The results show that the suppression of PEV is a general feature of any type of constitutive heterochromatin and that the intensity of suppression depends on its amount instead of some mappable factor on it. We also describe a clear dosage effect of Y heterochromatin on the viability of otherwise wild-type embryos and the modification of that effect by a specific gene mutation. Together, our results indicate that the correct balance between heterochromatin and euchromatin is essential for the normal genome expression and that this balance is genetically controlled. PMID:25053704

  13. Risk factors and safe dosage of levodopa for wearing-off phenomenon in Chinese patients with Parkinson's disease.

    PubMed

    Chen, Huimin; Fang, Jinping; Li, Fangfei; Gao, Liyan; Feng, Tao

    2015-07-01

    The objective of this study was to investigate the risk factors of wearing-off phenomenon in Parkinson's disease (PD) and propose safe dosage of levodopa to reduce wearing-off development based on Chinese cohort. Patients with PD who had taken levodopa (L-dopa) for at least 1 month were recruited. Wearing-off was diagnosed based on validated Chinese version of a patient self-rated 9-question Wearing-Off Questionnaire (WOQ-9) and clinical definition. Eleven variables (gender, disease duration at L-dopa initiation, disease duration at assessment, age at onset, age at assessment, H-Y stage, UPDRS III, L-dopa daily total dosage and dosage adjusted to weight, duration of L-dopa treatment, initial drug recipe) were included in our analysis. Univariate analysis, multivariate logistic regression analysis and decision tree classification model(DTC) were used to detect risk factors of wearing-off. Receiver operating characteristic (ROC) curve and DTC were used to investigate cut-off value of L-dopa to best predict wearing-off. Two hundred and thirty-four patients were investigated in our study, among whom 111 developed wearing-off. Patients with wearing-off tended to receive higher L-dopa dosage and endure longer duration of L-dopa treatment. L-Dopa dosage as 281 mg/day and 4.2 mg/kg/day by ROC, as well as 269 mg/day and 3.2 mg/kg/day by DTC were cut-off values for wearing-off. L-Dopa dosage and duration of L-dopa treatment were related to increased wearing-off development. Cumulative L-dopa dosage and L-dopa daily dosage were better predictive of wearing-off. Inadequate evidence was present for delayed L-dopa initiation. L-Dopa daily dosage no more than 275 mg or 4.2 mg/kg was regarded as safe.

  14. Les rivières et les sources de la Plaine du Cul-de-Sac: extrait du rapport sur les eaux souterraines de la Plaine du Cul-de-Sac

    USGS Publications Warehouse

    Taylor, George C.; Lemoine, Rémy C.

    1949-01-01

    Les principales rivières de la Plaine du Cul-de-Sac, la Rivière Grise ou Grande Rivière du Cul-de-Sac et la Rivière Blanche, prennent naissance sur le flanc Nord du Massif de la Selle à des altitudes de 1,300 à 1,800 mètres au dessus du niveau de la mer. Elles coulent à l’amont à travers des gorges profondes et sont éloignées de 9 Kms. dans la partie central de la bordure Sud de la plaine.

  15. [Biography of the outstanding acupuncturist DU Xiao-shan].

    PubMed

    Ding, Min; Lu, Rui-Qin; Du, Liang-Dong; Cao, Li; Lin, Tian-Yun

    2012-09-01

    Professor DU Xiao-shan 's academic thought and clinical experiences was introduced in this paper. He has noble medical ethics and is fair to the patients without distinction. He has great learning and rich practical experiences, and he specializes in all kinds of common diseases as well as many difficult and complicated cases. He never stops studying the ancients to make innovation and he creates the technique of the quick-puncture and slow-twist and DU's heat-reinforce method. He teaches to carry forward acupuncture and moxibustion and his achievements have become an important part of acupuncture and moxibustion science.

  16. Nondestructive and rapid concurrent estimation of paracetamol and nimesulide in their combined dosage form using Raman spectroscopic technique.

    PubMed

    Lakhwani, Gargi R; Sherikar, O D; Mehta, Priti J

    2013-03-01

    A rapid, nondestructive Raman spectroscopic method was developed for quantitative estimation of paracetamol and nimesulide in their combined dosage form. A Raman univariate calibration model was developed by measuring the peak intensities of paracetamol and nimesulide at 853 cm(-1) and 1336 cm(-1), respectively. The developed method was successfully applied for in situ, concurrent estimation of paracetamol and nimesulide in their combined dosage and method was also validated according to International Conference on Harmonisation guidelines. Thus, the developed Raman spectroscopic method can be applied for simultaneous estimation of paracetamol and nimesulide in their combined dosage form as a process analytical technology tool by pharmaceutical industries for routine quality control.

  17. Prescrire du cannabis fumé pour la douleur chronique non cancéreuse

    PubMed Central

    Kahan, Meldon; Srivastava, Anita; Spithoff, Sheryl; Bromley, Lisa

    2014-01-01

    Résumé Objectif Offrir des conseils préliminaires sur la prescription de cannabis fumé pour la douleur chronique avant la publication de lignes directrices officielles. Qualité des données Nous avons examiné les ouvrages scientifiques sur l’efficacité analgésique du cannabis fumé et les dommages causés par la consommation de cannabis à des fins médicales et récréatives. Nous avons élaboré des recommandations concernant les indications et les contre-indications du cannabis fumé, les précautions à prendre et son dosage et nous avons classé les recommandations en fonction du niveau des données probantes. La plupart des données probantes sont de niveau II (études observationnelles bien effectuées) et de niveau III (opinion d’experts). Message principal Le cannabis fumé pourrait être indiqué chez des patients souffrant de douleurs neuropathiques sévères qui n’ont pas répondu à des essais suffisants de cannabinoïdes pharmaceutiques et d’analgésiques standards (données probantes de niveau II). Le cannabis fumé est contre-indiqué chez les patients de 25 ans ou moins (données probantes de niveau II); ceux qui font actuellement ou ont fait par le passé une psychose ou encore ont de forts antécédents familiaux de psychose (données probantes de niveau II); ceux qui ont ou ont eu un problème de consommation de cannabis (données probantes de niveau III); ceux qui ont un problème actuel de toxicomanie ou d’alcoolisme (données probantes de niveau III); ceux qui ont une maladie cardiovasculaire ou respiratoire (données probantes de niveau III); ou celles qui sont enceintes ou planifient une grossesse (données probantes de niveau II). Il devrait être utilisé avec précaution par les patients qui fument du tabac (données probantes de niveau II), qui sont à risque accru de maladies cardiovasculaires (données probantes de niveau III), qui ont des troubles d’anxiété ou de l’humeur (données probantes de niveau II) ou

  18. Baisse du HDL-cholestérol indicateur du stress oxydatif dans le diabète de type 2

    PubMed Central

    Kabamba, Arsène Tshikongo; Bakari, Salvius Amuri; Longanga, Albert Otshudi; Lukumwena, Zet Kalala

    2014-01-01

    L'hypercholestérolémie est étroitement liée au stress oxydatif. Lorsqu'il y a trop de cholestérol qui circule dans le sang, il n'est pas utilisé en totalité par les cellules et il risque de s'accumuler dans les vaisseaux sanguins. Cela peut entrainer la formation des plaques d'athérosclérose qui gênent la circulation sanguine et provoquent des accidents cardiovasculaires. Le stress oxydatif apparait très tôt dans l'histoire des complications du diabète de type 2, et est lié à l'oxydation du glucose mais aussi à la peroxydation lipidique. Le cholestérol-HDL est un marqueur important du stress oxydatif par sa capacité à faciliter la métabolisation du cholestérol, sa baisse est souvent considérée comme la source de beaucoup d'inquiétudes. L'objectif est l’évaluation de la variation du taux de cholestérol-HDL, marqueur du stress oxydatif, chez les patients diabétiques de type 2 dans la population congolaise. Nous avons inclus dans cette étude prospective des cas témoins des patients diabétiques de type 2 reconnus et diagnostiqués, et des témoins non diabétiques appariés selon l’âge et le sexe. Parallèlement au bilan biologique classique, une analyse d'un des facteurs de risque du stress oxydatif a été réalisée: baisse de HDL-Cholestérol. L’âge moyen des 30 patients diabétiques (47,77±10,78 ans) était comparable à celui des 30 témoins (48,83±10,73 ans). Une baisse significative du cholestérol-HDL dans le sang était observée chez 100% des diabétiques et 50% des témoins (p=0,0000). L'augmentation du HDL cholestérol permet d’éliminer le mauvais cholestérol en excès en nettoyant les tissus et en ramenant le cholestérol vers le foie. Lors du diabète de type 2 on constate une baisse sanguine sensible du taux de HDL-cholestérol, qui est signe indicateur du stress oxydatif. PMID:25767660

  19. Facteurs liés au diagnostic tardif du cancer du sein: expérience du CHU Mohammed VI Marrakech

    PubMed Central

    Aloulou, Sofia; El Mahfoudi, Amal; El Omrani, Abdelhamid; Khouchani, Mouna

    2015-01-01

    Le cancer du sein est le premier cancer féminin en termes d'incidence et de mortalité. Au Maroc, il vient au premier rang des cancers de la femme avant celui du col utérin Il constitue un problème de santé publique. Son pronostic est étroitement lié au stade auquel le diagnostic est posé. Il s'agit d'une pathologie dont les moyens diagnostiques sont de nos jours développés, allant de la détection précoce à la mise en évidence de lésions infra-cliniques, ce qui a nettement amélioré le pronostic dans les pays développés. Ce travail que nous présentons a pour objectif d'identifier dans notre pratique quotidienne, les facteurs qui amènent les patientes à consulter à des stades tardifs. Une étude rétrospective a été menée de janvier 2012 à janvier 2013 portant sur 130 patientes porteuses d'un cancer du sein au sein du service d'onco-radiotherapie CHU Mohammed VI Marrakech. Un questionnaire a été élaboré et dument renseigné en ayant recours aux dossiers des malades. Ainsi 63,07% des patientes consultaient au-delà de six mois avec un délai moyen de consultation de 8,47 mois avec comme motif de consultation des lésions classées T4 dans 27,69%, et des tumeurs d'emblée métastatiques dans 13,84%. Les facteurs retrouvés à l'interrogatoire étaient le manque de moyens financiers 40%, l’éloignement des structures sanitaires dans 23%, les habitudes socioculturelles avec les traitements traditionnels en première intention 20%, et l'insuffisance de prise en charge thérapeutique 7%. Cependant, pris individuellement, aucune concordance significative n’était retrouvée entre ces facteurs et le long délai diagnostique. Dans notre pratique, c'est la conjonction de la triade ignorance, indigence et habitudes socioculturelles qui constituent le facteur essentiel du diagnostic tardif des cancers du sein. PMID:26327999

  20. Le traitement conservateur du cancer du sein: expérience d'une équipe tunisienne

    PubMed Central

    Dimassi, Kaouther; Gharsa, Anissa; Chanoufi, Mohammed Badis; Sfar, Ezzeddine; Chelli, Dalenda

    2014-01-01

    En Tunisie, le cancer du sein touche des femmes jeunes avec une taille moyenne au moment du diagnostic à 5 cm. Ces particularités font que la chirurgie radicale reste prédominante. Nous présentons dans ce travail l'expérience de notre équipe en matière de chirurgie conservatrice du cancer du sein. Le but de ce travail est d’évaluer les résultats de ce traitement. Etude rétrospective longitudinale, sur une période de 75 mois. Nous avons inclus toutes les patientes ayant bénéficié d'un traitement conservateur pour une tumeur maligne du sein. Ont été analysés: les caractéristiques épidémiologiques, les aspects radiologiques et histologiques. Le suivi des malades s'est basé sur la détection des récidives. Nous avons évalué le résultat esthétique à la fin de la radiothérapie. Le traitement conservateur a été réalisé dans 23.8% des cas. Le taux de récidives locales était de 6.8% avec une corrélation significative pour une taille tumorale > 30 mm (p= 0.009), l'association d'une composante intracanalaire (p= 0.035), le statut triple négatif (p= 0.003) et des marges d'exérèse < 5mm sans recoupes per-opératoires (p = 0.045). Les facteurs suivants étaient significativement liés au risque de survenue de métastases à distance: le statut triple négatif (p= 0.003), taille tumorale > 30mm (p = 0.006) et l'atteinte ganglionnaire (p = 0.001). Le résultat esthétique était satisfaisant dans 90% des cas. L'augmentation du nombre de patientes pouvant bénéficier d'une chirurgie conservatrice, doit passer impérativement par le développement et la promotion du diagnostic précoce et du dépistage par la mammographie. PMID:25810795