Science.gov

Sample records for dosage spectrophotometriqiue du

  1. 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.

  2. X-Chromosome dosage compensation.

    PubMed

    Meyer, Barbara J

    2005-01-01

    In mammals, flies, and worms, sex is determined by distinctive regulatory mechanisms that cause males (XO or XY) and females (XX) to differ in their dose of X chromosomes. In each species, an essential X chromosome-wide process called dosage compensation ensures that somatic cells of either sex express equal levels of X-linked gene products. The strategies used to achieve dosage compensation are diverse, but in all cases, specialized complexes are targeted specifically to the X chromosome(s) of only one sex to regulate transcript levels. In C. elegans, this sex-specific targeting of the dosage compensation complex (DCC) is controlled by the same developmental signal that establishes sex, the ratio of X chromosomes to sets of autosomes (X:A signal). Molecular components of this chromosome counting process have been defined. Following a common step of regulation, sex determination and dosage compensation are controlled by distinct genetic pathways. C. elegans dosage compensation is implemented by a protein complex that binds both X chromosomes of hermaphrodites to reduce transcript levels by one-half. The dosage compensation complex resembles the conserved 13S condensin complex required for both mitotic and meiotic chromosome resolution and condensation, implying the recruitment of ancient proteins to the new task of regulating gene expression. Within each C. elegans somatic cell, one of the DCC components also participates in the separate mitotic/meiotic condensin complex. Other DCC components play pivotal roles in regulating the number and distribution of crossovers during meiosis. The strategy by which C. elegans X chromosomes attract the condensin-like DCC is known. Small, well-dispersed X-recognition elements act as entry sites to recruit the dosage compensation complex and to nucleate spreading of the complex to X regions that lack recruitment sites. In this manner, a repressed chromatin state is spread in cis over short or long distances, thus establishing the

  3. 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.

  4. 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. Mol Cancer Ther; 15(3); 347-53. ©2016 AACR. PMID:26916116

  5. Estimated Radiation Dosage on Mars

    NASA Technical Reports Server (NTRS)

    2002-01-01

    This global map of Mars shows the estimated radiation dosages from cosmic rays reaching the surface, a serious health concern for any future human exploration of the planet.

    The estimates are based on cosmic-radiation measurements by the Mars radiation environment experiment, an instrument on NASA's Mars 2000 Odyssey spacecraft, plus information about Mars' surface elevations from the laser altimeter instrument on NASA's Mars Global Surveyor. The areas of Mars expected to have the lowest levels of cosmic radiation are where the elevation is lowest, because those areas have more atmosphere above them to block out some of the radiation. Earth's thick atmosphere shields us from most cosmic radiation, but Mars has a much thinner atmosphere than we have on Earth.

    The colors in the map refer to the estimated annual dose equivalent in rems, a unit of radiation dose. The range is generally from 10 rems(color-coded dark blue) to 20 rems (color coded dark red). Radiation exposure for astronauts on the International Space Station in Earth orbit is typically equivalent to an annualized rate of 20 to 40 rems.

    NASA's Jet Propulsion Laboratory, Pasadena, Calif. manages the 2001 Mars Odyssey and Mars Global Surveyor missions for NASA's Office of Space Science, Washington D.C. The Mars radiation environment experiment was developed by NASA's Johnson Space Center, Houston. Lockheed Martin Astronautics, Denver, is the prime contractor for Odyssey, and developed and built the orbiter. Mission operations are conducted jointly from Lockheed Martin and from JPL, a division of the California Institute of Technology in Pasadena.

  6. Advances in solid dosage form manufacturing technology.

    PubMed

    Andrews, Gavin P

    2007-12-15

    Currently, the pharmaceutical and healthcare industries are moving through a period of unparalleled change. Major multinational pharmaceutical companies are restructuring, consolidating, merging and more importantly critically assessing their competitiveness to ensure constant growth in an ever-more demanding market where the cost of developing novel products is continuously increasing. The pharmaceutical manufacturing processes currently in existence for the production of solid oral dosage forms are associated with significant disadvantages and in many instances provide many processing problems. Therefore, it is well accepted that there is an increasing need for alternative processes to dramatically improve powder processing, and more importantly to ensure that acceptable, reproducible solid dosage forms can be manufactured. Consequently, pharmaceutical companies are beginning to invest in innovative processes capable of producing solid dosage forms that better meet the needs of the patient while providing efficient manufacturing operations. This article discusses two emerging solid dosage form manufacturing technologies, namely hot-melt extrusion and fluidized hot-melt granulation. PMID:17855217

  7. CNS myelination and PLP gene dosage.

    PubMed

    Woodward, K; Malcolm, S

    2001-08-01

    The phenomenon of gene dosage effects demonstrates that the mechanisms of some genetic diseases are best recognised at the genomic level. Classical gene mutation screening approaches utilising PCR are unsuccessful in unravelling the basis of disease because the gene sequence is unaltered and only the copy number is different. Techniques for detecting DNA dosage are required. Examples of haploinsufficiency and gene deletions are well documented, but increased gene dosage is also an important genetic mechanism in disorders involving myelin proteins in the central (CNS) and peripheral nervous system (PNS). Here we review the dosage effects and mutations of the proteolipid protein (PLP) gene that causes Pelizaeus-Merzbacher disease (PMD) and spastic paraplegia Type 2 (SPG2) disorders of CNS myelination. Similarities are drawn with the peripheral neuropathies Charcot-Marie-Tooth disease Type 1 (CMT1A) and hereditary neuropathy with liability to pressure palsies (HNPP) that are also caused by dosage effects and mutations in a single myelin protein gene (peripheral myelin protein 22, PMP-22). We compare the different mutational mechanisms in man and analogous mouse models that suggest a function for PLP beyond its structural role in myelin. We focus on the increased dosage of the PLP gene that is the major cause of PMD and results from a submicroscopic duplication of Xq22. Other clinical phenotypes may arise from gene dosage imbalance with the potential effect of submicroscopic duplications and deletions of the genome being underestimated. Genome sequencing may identify intrinsic structural properties of the DNA with greater susceptibility to these rearrangements and thereby reflect structural changes in the genome. PMID:11535114

  8. [Evaluation of voriconazole oral dosage in Japan].

    PubMed

    Hamada, Yukihiro; Kawasumi, Noriyo; Hirai, Jun; Yamagishi, Yuka; Mikamo, Hiroshige

    2014-10-01

    Voriconazole (VRCZ), a broad-spectrum triazole, is served in two dosage forms-injection and oral. VRCZ is difference dosage of oral and intravenous administration writing a medical package insert in Japan. 6 mg/kg intravenous injection (IV) twice daily for first day as initial loading dose, followed by 3-4 mg/kg IV twice daily between meals is recommended. 300 mg orally twice daily for first day as initial loading dose, followed by 150-200 mg orally twice daily between meals is recommended. Patients weighing over 40 kg, 200 mg orally twice daily between meals is recommended. Patients weighing under 40 kg, 100 mg orally twice daily between meals is recommended, increase to 150 mg twice daily if inadequate response. This study evaluated VRCZ trough concentration and oral dosage in the 23 cases which administered VRCZ to analysis for TDM in Aichi University Hospital. Spearman rank correlation coefficient was calculated to examine relationships among variables. The level of statistical significance was set at p=0.05. All data were analyzed and processed on JMP 8 (SAS Institute Japan). There was a significant positive correlation between VRCZ trough concentration and dose/weight (r=0.47 p<0.05). In this result, VRCZ oral dosage is appropriate to administer dose/weight (mg/kg) twice a day as same as IV. PMID:25566590

  9. "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 child readers. (SG)

  10. Higher unit dosage of psychotropic drugs.

    PubMed

    Burrell, C D

    1975-12-01

    The realities of the marketplace dictate that pharmaceutical companies seek to develop higher unit dosage forms. Technical problems not infrequently hinder such development. In low doses once-a-day medication with psychotropics is possible and practical. The potential for adverse reactions frequently renders it desirable to divide higher daily doses into two separate doses, one given in the morning and the other in the evening. PMID:1233527

  11. Study of dosage compensation in Drosophila.

    PubMed Central

    Chiang, Pei-Wen; Kurnit, David M

    2003-01-01

    Using a sensitive RT-QPCR assay, we analyzed the regulatory effects of sex and different dosage compensation mutations in Drosophila. To validate the assay, we showed that regulation for several genes indeed varied with the number of functional copies of that gene. We then confirmed that dosage compensation occurred for most genes we examined in male and female flies. Finally, we examined the effects on regulation of several genes in the MSL pathway, presumed to be involved in sex-dependent determination of regulation. Rather than seeing global alterations of either X chromosomal or autosomal genes, regulation of genes on either the X chromosome or the autosomes could be elevated, depressed, or unaltered between sexes in unpredictable ways for the various MSL mutations. Relative dosage for a given gene between the sexes could vary at different developmental times. Autosomal genes often showed deranged regulatory levels, indicating they were in pathways perturbed by X chromosomal changes. As exemplified by the BR-C locus and its dependent Sgs genes, multiple genes in a given pathway could exhibit coordinate regulatory modulation. The variegated pattern shown for expression of both X chromosomal and autosomal loci underscores the complexity of gene expression so that the phenotype of MSL mutations does not reflect only simple perturbations of genes on the X chromosome. PMID:14668373

  12. 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

  13. 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. PMID:6748671

  14. The du Bois sign.

    PubMed

    Voelpel, James H; Muehlberger, Thomas

    2011-03-01

    According to the current literature, the term "du Bois sign" characterizes the condition of a shortened fifth finger as a symptom of congenital syphilis, Down syndrome, dyscrania, and encephalic malformation. Modern medical dictionaries and text books attribute the eponym to the French gynecologist Paul Dubois (1795-1871). Yet, a literature analysis revealed incorrect references to the person and unclear definitions of the term. Our findings showed that the origin of the term is based on observations made by the Swiss dermatologist Charles du Bois (1874-1947) in connection with congenital syphilis. In addition, a further eponymical fifth finger sign is closely associated with the du Bois sign. In conclusion, the du Bois sign has only limited diagnostic value and is frequently occurring in the normal healthy population. PMID:21263293

  15. Bioavailability of valsartan oral dosage forms.

    PubMed

    Sunkara, Gangadhar; Bende, Girish; Mendonza, Anisha E; Solar-Yohay, Susan; Biswal, Shibadas; Neelakantham, Srikanth; Wagner, Robert; Flarakos, Jimmy; Zhang, Yiming; Jarugula, Venkateswar

    2014-03-01

    The oral bioavailability of valsartan from extemporaneous suspension and solution formulations were evaluated relative to tablet formulation in two separate open-label, randomized crossover studies in healthy adults. In both studies, the plasma concentrations of valsartan after oral administration were analyzed using validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods, and the corresponding pharmacokinetic parameters were estimated using noncompartmental analysis. The peak plasma concentration (Cmax ) and area under the concentration time-curves (AUC(0-∞) ) of valsartan from the extemporaneous suspension were higher by 1.93- and 1.56-fold, respectively, relative to the tablet formulation (P < .001). The Cmax and AUC(0-∞) of valsartan from the oral solution were higher by 2.21- and 1.74-fold, respectively, relative to the tablet formulation (P < .001). These results indicate that both rate and extent of absorption of valsartan are higher in the two liquid dosage forms (extemporaneous suspension and solution formulations) relative to the solid oral dosage form (tablet formulation). PMID:27128457

  16. Evaluation of new indomethacin dosage forms.

    PubMed

    Waller, E S

    1983-01-01

    Indomethacin, an indole derivative nonsteroidal anti-inflammatory drug, has been available since the early 1960s in gelatin capsules. In 1982, a sustained release product, Indocin SR, was marketed. Awaiting marketing approval is a unique controlled release form of indomethacin, Indos. The disposition of indomethacin includes enterohepatic cycling and extensive metabolism to inactive metabolites. Enterohepatic cycling makes interpretation of bioavailability estimates of indomethacin dosage forms difficult. The relationship of indomethacin plasma concentration to therapeutic effects and side effects is inconclusive. It appears in vivo prostaglandin inhibition occurs at very low plasma concentrations that are achievable with all available dosage forms. Indocin SR is a sustained release capsule of indomethacin designed to deliver 25 mg of drug immediately and 50 mg gradually. Absolute bioavailability of the product is 80%. The plasma concentration-time curves do not show good sustained release characteristics; after four hours plasma concentrations resemble those seen with a single dose of regular capsule. The cost compared with Indocin is competitive. Indos is a zero-order release form of indomethacin. It is a unique drug delivery system that shows good controlled release characteristics. Bioavailability is 85%. Both Indocin SR and Indos are apparently therapeutically equivalent to indomethacin capsules. In elderly patients, Indos has been shown to be associated with fewer side effects than Indocin. Both Indocin SR and Indos have the advantage of once or twice daily dosing. PMID:6361702

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

    PubMed

    Chen, Zhen-Xia; Oliver, Brian

    2015-06-01

    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. PMID:25850426

  18. [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. PMID:21796994

  19. 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... Dithiazanine iodide oral dosage forms....

  20. 21 CFR 520.540 - Dexamethasone oral dosage forms.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Dexamethasone oral dosage forms. 520.540 Section 520.540 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Dexamethasone oral dosage forms....

  1. 21 CFR 520.540 - Dexamethasone oral dosage forms.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Dexamethasone oral dosage forms. 520.540 Section 520.540 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Dexamethasone oral dosage forms....

  2. 21 CFR 520.540 - Dexamethasone oral dosage forms.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Dexamethasone oral dosage forms. 520.540 Section 520.540 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Dexamethasone oral dosage forms....

  3. 21 CFR 520.540 - Dexamethasone oral dosage forms.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Dexamethasone oral dosage forms. 520.540 Section 520.540 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Dexamethasone oral dosage forms....

  4. 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 520.2345 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Tetracycline oral dosage forms....

  5. 21 CFR 520.88 - Amoxicillin oral dosage forms.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 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...

  6. 21 CFR 520.88 - Amoxicillin oral dosage forms.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 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...

  7. 21 CFR 520.88 - Amoxicillin oral dosage forms.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 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...

  8. 21 CFR 520.88 - Amoxicillin oral dosage forms.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 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...

  9. 21 CFR 520.390 - Chloramphenicol oral dosage forms.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Chloramphenicol oral dosage forms. 520.390 Section 520.390 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Chloramphenicol oral dosage forms....

  10. 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... Chloramphenicol oral dosage forms....

  11. 21 CFR 520.390 - Chloramphenicol oral dosage forms.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Chloramphenicol oral dosage forms. 520.390 Section 520.390 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Chloramphenicol oral dosage forms....

  12. 21 CFR 520.390 - Chloramphenicol oral dosage forms.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Chloramphenicol oral dosage forms. 520.390 Section 520.390 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Chloramphenicol oral dosage forms....

  13. 21 CFR 520.390 - Chloramphenicol oral dosage forms.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Chloramphenicol oral dosage forms. 520.390 Section 520.390 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Chloramphenicol oral dosage forms....

  14. 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... Dexamethasone oral dosage forms....

  15. 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...

  16. 21 CFR 520.2325 - Sulfaquinoxaline oral dosage forms.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Sulfaquinoxaline oral dosage forms. 520.2325 Section 520.2325 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Sulfaquinoxaline oral dosage forms....

  17. 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 Section 520.2325 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Sulfaquinoxaline oral dosage forms....

  18. 21 CFR 520.1044 - Gentamicin sulfate oral dosage forms.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Gentamicin sulfate oral dosage forms. 520.1044 Section 520.1044 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 § 520.1044...

  19. 21 CFR 520.1044 - Gentamicin sulfate oral dosage forms.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Gentamicin sulfate oral dosage forms. 520.1044 Section 520.1044 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 § 520.1044...

  20. 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 Section 520.1044 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 § 520.1044...

  1. 21 CFR 520.1044 - Gentamicin sulfate oral dosage forms.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Gentamicin sulfate oral dosage forms. 520.1044 Section 520.1044 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 § 520.1044...

  2. 21 CFR 520.1044 - Gentamicin sulfate oral dosage forms.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Gentamicin sulfate oral dosage forms. 520.1044 Section 520.1044 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 § 520.1044...

  3. Problem solved: dosage calculation in a nursing program.

    PubMed

    Jackson, Nancy V; De Carlo, James J

    2011-01-01

    Patient safety, including the safe administration of medications, is an essential component of nursing practice. However, helping students calculate medication dosages has continually challenged faculty members and students. The authors describe a comprehensive approach to teaching and evaluating dosage calculation. Common barriers to helping students master necessary math skills required for accuracy are addressed. PMID:21330900

  4. 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 Section 522.1660 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... § 522.1660 Oxytetracycline injectable dosage forms....

  5. 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...

  6. 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...

  7. 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....

  8. 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....

  9. 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...

  10. 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....

  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, 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...

  13. 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. 522.1222 Section 522.1222 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... ANIMAL DRUGS § 522.1222 Ketamine hydrochloride injectable dosage forms....

  14. 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 522.313 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 NEW ANIMAL...

  15. 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. 522.1222 Section 522.1222 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... ANIMAL DRUGS § 522.1222 Ketamine hydrochloride injectable dosage forms....

  16. 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. 522.1222 Section 522.1222 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... ANIMAL DRUGS § 522.1222 Ketamine hydrochloride injectable dosage forms....

  17. 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. 522.1222 Section 522.1222 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... ANIMAL DRUGS § 522.1222 Ketamine hydrochloride injectable dosage forms....

  18. 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. PMID:19883250

  19. Aminophylline Dosage In Asthma Exacerbations in Children: A Systematic Review

    PubMed Central

    2016-01-01

    Background Adequate asthma treatment of childhood exacerbations with IV aminophylline depends on appropriate dosage. Recommendations to aim for a target therapeutic range may be inappropriate as serum concentrations correlate poorly with clinical improvement. This review aims to evaluate the evidence for the optimum dosage strategy of intravenous aminophylline in children suffering an exacerbation of asthma. Methods A systematic review comparing dosage regimens of intravenous aminophylline in children suffering an exacerbation of asthma. Primary outcomes were time until resolution of symptoms, mortality and need for mechanical ventilation. Secondary outcomes were date until discharge criteria are met, actual discharge and adverse effects. Data sources CENTRAL, CINAHL, MEDLINE and Web of Science. Search performed in March 2016 Eligibility criteria Studies using intravenous aminophylline in children with an acute exacerbation of asthma which reported the dosage and clinical outcomes. Findings 14 RCTs were included. There is a poor relationship between the dosage administered to children and symptom resolution, length of stay or need for mechanical ventilation. This study is limited due to its use of indirect evidence. Conclusion The currently recommended dosage regimens may not represent the optimum safety and efficacy of intravenous aminophylline. There is a need to develop the evidence base correlating dosage with patient centered clinical outcomes, to improve prescribing practices. PMID:27483163

  20. Gene dosage effects on the synthesis of maltase in yeast.

    PubMed Central

    Mowshowitz, D B

    1979-01-01

    Inbred strains of Saccharomyces cerevisiae carrying MAL1, MAL2, or MAL6 in a common background were used to construct (i) homo- or heterozygous diploids carrying one or two active alleles of a single MAL locus (MAL1, MAL2, or MAL6) and (ii) triploids carrying one, two, or three active alleles of MAL2. The diploid and triploid strains were used to investigate gene dosage effects of the differential rate of maltase synthesis (delta enzyme activity/delta growth) and the kinetics of induction (for MAL2). All three MAL loci exhibited a gene dosage effect on the differential rate of maltase synthesis; MAL2 also exhibited a gene dosage effect on the kinetics of induction. The dosage effects of the MAL1 and MAL6 loci were additive, but the effects of the MAL2 locus were not; the magnitude of the MAL2 gene dosage effect decreased with increasing dosage. These results are compatible with the current genetic evidence that the MAL genes are regulatory loci if the product(s) of the MAL1 and MAL6 locus is produced in limiting amounts but the product(s) of the MAL2 locus is produced in excess, except at very low genes dosages. PMID:374342

  1. Extending the market exclusivity of therapeutic antibodies through dosage patents.

    PubMed

    Storz, Ulrich

    2016-07-01

    Dosage patents are one way to extend the market exclusivity of an approved drug beyond the lifetime of the patent that protects the drug as such. Dosage patents may help to compensate the applicant for the long period where the active pharmaceutical ingredient as such is already under patent prosecution, but not on the market yet, due to lengthy development and approval procedures. This situation erodes part of the time the drug is marketed under patent protection. Dosage patents filed at a later date can provide remedy for this problem. Examples of successful and unsuccesful attempts, and the reasons for the respective outcomes, are provided in this article. PMID:27115842

  2. Comparative safety of testosterone dosage forms

    PubMed Central

    Layton, J. Bradley; Meier, Christoph R.; Sharpless, Julie L.; Stürmer, Til; Jick, Susan S.; Brookhart, M. Alan

    2015-01-01

    Importance Increases in testosterone use and mixed reports of adverse events have raised concerns about the cardiovascular safety of testosterone. Testosterone is available in several delivery mechanisms with varying pharmacokinetics; injections cause spikes in testosterone levels, while transdermal patches and gels cause more subtle but sustained increases. The comparative cardiovascular safety of gels, injections and patches has not been studied. Objective To determine the comparative cardiovascular safety of testosterone injections, patches, and gels. Design Retrospective cohort study. Setting Administrative claims from a commercially-insured and Medicare population in the United States, and general practitioner records from the United Kingdom, years 2000 – 2012 Participants Adult (18+), male initiators of testosterone patches, gels, or injections following 180 days free of any testosterone use Exposure New initiation of a testosterone dosage form, followed for up to one year Main Outcomes and Measures In- or outpatient medical records, diagnoses, or claims for: cardio- and cerebrovascular events, including myocardial infarction (MI), unstable angina, stroke, composite acute event (MI, unstable angina, or stroke); venous thromboembolism (VTE); mortality, and all-cause hospitalization. Results We identified 431,687 testosterone initiators between the 3 datasets: 36% injection, 9% patch, 55% gel. Medicare had a majority of injection initiators (51%); the US commercially-insured population had majority gel initiators (56%); the United Kingdom had equal proportions of injections and gels (~41%). When compared to gels, injection initiators had higher hazards of CV events (MI, UA, and stroke) (HR=1.26, 95% CI: 1.18–1.35), hospitalization (HR=1.16, 95% CI: 1.13–1.18), and death (HR=1.34, 95% CI: 1.15–1.56), but not VTE (HR=0.92, 95% CI: 0.76–1.11). Patches did not confer increased hazards of CV events compared to gels (HR=1.10, 95% CI: 0.94–1

  3. Partial dosage compensation in Strepsiptera, a sister group of beetles.

    PubMed

    Mahajan, Shivani; Bachtrog, Doris

    2015-02-01

    Sex chromosomes have evolved independently in many different taxa, and so have mechanisms to compensate for expression differences on sex chromosomes in males and females. Different clades have evolved vastly different ways to achieve dosage compensation, including hypertranscription of the single X in male Drosophila, downregulation of both X's in XX Caenorhabditis, or inactivation of one X in female mammals. In the flour beetle Tribolium, the X appears hyperexpressed in both sexes, which might represent the first of two steps to evolve dosage compensation along the paths mammals may have taken (i.e., upregulation of X in both sexes, followed by inactivation of one X in females). Here we test for dosage compensation in Strepsiptera, a sister taxon to beetles. We identify sex-linked chromosomes in Xenos vesparum based on genomic analysis of males and females, and show that its sex chromosome consists of two chromosomal arms in Tribolium: The X chromosome that is shared between Tribolium and Strepsiptera, and another chromosome that is autosomal in Tribolium and another distantly related Strepsiptera species, but sex-linked in X. vesparum. We use RNA-seq (RNA sequencing) to show that dosage compensation along the X of X. vesparum is partial and heterogeneous. In particular, genes that are X-linked in both beetles and Strepsiptera appear fully dosage compensated probably through downregulation in both sexes, whereas genes on the more recently added X segment have evolved only partial dosage compensation. In addition, reanalysis of published RNA-seq data suggests that Tribolium has evolved dosage compensation, without hypertranscribing the X in females. Our results demonstrate that patterns of dosage compensation are highly variable across sex-determination systems and even within species. PMID:25601100

  4. Partial Dosage Compensation in Strepsiptera, a Sister Group of Beetles

    PubMed Central

    Mahajan, Shivani; Bachtrog, Doris

    2015-01-01

    Sex chromosomes have evolved independently in many different taxa, and so have mechanisms to compensate for expression differences on sex chromosomes in males and females. Different clades have evolved vastly different ways to achieve dosage compensation, including hypertranscription of the single X in male Drosophila, downregulation of both X’s in XX Caenorhabditis, or inactivation of one X in female mammals. In the flour beetle Tribolium, the X appears hyperexpressed in both sexes, which might represent the first of two steps to evolve dosage compensation along the paths mammals may have taken (i.e., upregulation of X in both sexes, followed by inactivation of one X in females). Here we test for dosage compensation in Strepsiptera, a sister taxon to beetles. We identify sex-linked chromosomes in Xenos vesparum based on genomic analysis of males and females, and show that its sex chromosome consists of two chromosomal arms in Tribolium: The X chromosome that is shared between Tribolium and Strepsiptera, and another chromosome that is autosomal in Tribolium and another distantly related Strepsiptera species, but sex-linked in X. vesparum. We use RNA-seq (RNA sequencing) to show that dosage compensation along the X of X. vesparum is partial and heterogeneous. In particular, genes that are X-linked in both beetles and Strepsiptera appear fully dosage compensated probably through downregulation in both sexes, whereas genes on the more recently added X segment have evolved only partial dosage compensation. In addition, reanalysis of published RNA-seq data suggests that Tribolium has evolved dosage compensation, without hypertranscribing the X in females. Our results demonstrate that patterns of dosage compensation are highly variable across sex-determination systems and even within species. PMID:25601100

  5. 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.

  6. Kyste hydatique primitif du sein

    PubMed Central

    Mouslik, Rabii; Settaf, Abdellatif; Elalami, Yacir; Lahnini, Hicham; Lahlou, Khalid; Chad, Bouziane

    2012-01-01

    Le kyste hydatique du sein est une parasitose rare même dans les pays endémiques. Nous rapportons une nouvelle observation d'une patiente de 30 ans qui présentait une masse du sein gauche. Le diagnostic de kyste hydatique du sein a été évoqué devant les données de l'examen clinique et de la mammographie couplée à l’échographie. Le geste chirurgical a consisté en une kystectomie. L'examen anatomopathologique de la pièce opératoire a confirmé le diagnostic. PMID:23133704

  7. 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. PMID:3840551

  8. Homogeneity study of ointment dosage forms by infrared imaging spectroscopy.

    PubMed

    Carneiro, Renato Lajarim; Poppi, Ronei Jesus

    2012-01-25

    Ointment dosage forms are semi-solid preparations intended for local or transdermal delivery of active substances usually for application to the skin and it is important that they present a homogeneous appearance. In this work, a study of the homogeneity of a tacrolimus ointment dosage form was performed using infrared imaging spectroscopy coupled with principal component analysis (PCA) and multivariate curve resolution with alternating least squares (MCR-ALS) to interpret the imaging data. Optical visible microscopy images indicated possible phase separation in the ointment and, based on the results presented by distribution concentration maps from infrared imaging, it was possible to conclude that, in fact, there was phase separation incorporated in the ointment. Thus, infrared imaging spectroscopy associated to PCA and MCR-ALS is demonstrated to be a powerful tool for the development process of ointment dosage forms. PMID:22018891

  9. No X-chromosome dosage compensation in human proteomes.

    PubMed

    Chen, Xiaoshu; Zhang, Jianzhi

    2015-06-01

    The X and Y chromosomes of placental and marsupial mammals originated from a pair of autosomes. Ohno proposed that the expression levels of X-linked genes must have been doubled in males to compensate for the degeneration of their Y homologs. Recent mRNA sequencing experiments, however, found at most weak or infrequent X-chromosome dosage compensation. Nonetheless, dosage compensation need not occur at the mRNA level, because ultimately it is the protein concentration that matters. Analyzing human proteomic data from 22 tissues, we here report that X upregulation is absent at the protein level, indicating that Ohno's hypothesis is also invalid at the protein level. PMID:25697342

  10. Dosage-based parameters for characterization of puff dispersion results.

    PubMed

    Berbekar, Eva; Harms, Frank; Leitl, Bernd

    2015-01-01

    A set of parameters is introduced to characterize the dispersion of puff releases based on the measured dosage. These parameters are the dosage, peak concentration, arrival time, peak time, leaving time, ascent time, descent time and duration. Dimensionless numbers for the scaling of the parameters are derived from dimensional analysis. The dimensionless numbers are tested and confirmed based on a statistically representative wind tunnel dataset. The measurements were carried out in a 1:300 scale model of the Central Business District in Oklahoma City. Additionally, the effect of the release duration on the puff parameters is investigated. PMID:25278155

  11. World-wide radiation dosage calculations for air crew members.

    PubMed

    O'Brien, K; Smart, D F; Shea, M A; Felsberger, E; Schrewe, U; Friedberg, W; Copeland, K

    2003-01-01

    A greatly improved version of the computer program to calculate radiation dosage to air crew members is now available. Designated CARI-6, this program incorporates an updated geomagnetic cutoff rigidity model and a revision of the primary cosmic ray spectrum based on recent work by Gaisser and Stanev (1998). We believe CARI-6 provides the most accurate available method for calculating the radiation dosage to air crew members. The program is now utilized by airline companies around the world and provides unification for subsequent world-wide studies on the effects of natural radiation on aircrew members. PMID:14503487

  12. Estimation of drug dosage regimens with a pharmacokinetic slide rule.

    PubMed

    Straughn, A B; Cruze, C A; Meyer, M C

    1977-02-01

    A pharmacokinetic slide rule to facilitate the computations based on relatively simple pharmacokinetic principles involved in the development of individualized drug dosage regimens is described. The calculations are based on the assumption that the body can be conceived as a one-compartment open model with drug elimination proceeding by apparent first-order kinetics. Examples are presented (1) to illustrate the clinical application of a slide rule to compute the time-course of drug in the body, (2) to calculate steady-state maximum and minimum levels, and accumulation during multiple dosage and (3) to estimate appropriate maintenance doses and intravenous infusion rates. PMID:842548

  13. 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…

  14. Recent progress and open questions in Drosophila dosage compensation.

    PubMed

    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

  15. 21 CFR 520.1448 - Monensin oral dosage forms.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Monensin oral dosage forms. 520.1448 Section 520.1448 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... starting line). The loss on drying is not more than 10 percent when dried in vacuum at 60 °C for 2 hours....

  16. 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 520.1448 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... starting line). The loss on drying is not more than 10 percent when dried in vacuum at 60 °C for 2 hours....

  17. 21 CFR 520.1448 - Monensin oral dosage forms.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Monensin oral dosage forms. 520.1448 Section 520.1448 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... starting line). The loss on drying is not more than 10 percent when dried in vacuum at 60 °C for 2 hours....

  18. 21 CFR 201.55 - Statement of dosage.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 4 2011-04-01 2011-04-01 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...

  19. 21 CFR 201.55 - Statement of dosage.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 4 2013-04-01 2013-04-01 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...

  20. 21 CFR 201.55 - Statement of dosage.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 4 2012-04-01 2012-04-01 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...

  1. 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...

  2. 21 CFR 201.55 - Statement of dosage.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 4 2014-04-01 2014-04-01 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...

  3. 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...

  4. 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... Administration (FDA) is amending the animal drug regulations to reflect the original approval of a new animal.... 801-808. List of Subjects in 21 CFR Part 520 Animal drugs. 0 Therefore, under the Federal Food,...

  5. 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…

  6. 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

  7. 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

  8. Dosage compensation of the sex chromosomes and autosomes.

    PubMed

    Disteche, Christine M

    2016-08-01

    Males are XY and females are XX in most mammalian species. Other species such as birds have a different sex chromosome make-up: ZZ in males and ZW in females. In both types of organisms one of the sex chromosomes, Y or W, has degenerated due to lack of recombination with its respective homolog X or Z. Since autosomes are present in two copies in diploid organisms the heterogametic sex has become a natural "aneuploid" with haploinsufficiency for X- or Z-linked genes. Specific mechanisms have evolved to restore a balance between critical gene products throughout the genome and between males and females. Some of these mechanisms were co-opted from and/or added to compensatory processes that alleviate autosomal aneuploidy. Surprisingly, several modes of dosage compensation have evolved. In this review we will consider the evidence for dosage compensation and the molecular mechanisms implicated. PMID:27112542

  9. 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. PMID:27170865

  10. 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

  11. Effect of different curcumin dosages on human gall bladder.

    PubMed

    Rasyid, Abdul; Rahman, Abdul Rashid Abdul; Jaalam, Kamaruddin; Lelo, Aznan

    2002-01-01

    Our previous study demonstrated that curcumin, an active compound of Curcuma xanthorrhiza and C. domestica, produces a positive cholekinetic effect. A 20 mg amount of curcumin is capable of contracting the gall bladder by up to 29% within an observation time of 2 h. The aim of the current study was to define the dosage of curcumin capable of producing a 50% contraction of the gall bladder, and to determine if there is a linear relationship between doubling the curcumin dosage and the doubling of gall bladder contraction. A randomised, single-blind, three-phase, crossover-designed examination was carried out on 12 healthy volunteers. Ultrasonography was carried out serially to measure the gall bladder volume. The data obtained was analysed by analysis of variance (ANOVA). The fasting volumes of gall bladders were similar (P > 0.50), with 17.28 +/- 5.47 mL for 20 mg curcumin, 18.34 +/- 3.75 mL for 40 mg and 18.24 +/- 3.72 mL for 80 mg. The percentage decrease in gall bladder volume 2 h after administration of 20, 40 and 80 mg was 34.10 +/- 10.16, 51.15 +/- 8.08 and 72.25 +/- 8.22, respectively, which was significantly different (P < 0.01). On the basis of the present findings, it appears that the dosage of cucumin capable of producing a 50% contraction of the bladder was 40 mg. This study did not show any linear relationship between doubling curcumin dosage and the doubling of gall bladder contraction. PMID:12495265

  12. 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. PMID:27376899

  13. 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.

  14. 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

  15. Validation of a simplified netilmicin dosage regimen in infants.

    PubMed

    Klingenberg, Claus; Småbrekke, Lars; Lier, Tore; Flaegstad, Trond

    2004-01-01

    The aim of this study was to validate a simplified high-dosage, extended-interval netilmicin dosage regimen for infants. A total of 129 infants receiving 163 treatment courses of netilmicin (6 mg kg every 24 or 36 h depending on gestational age (GA), postnatal age and postmenstrual age) was analysed. Serum netilmicin concentrations were monitored before (Cmin), 30 min (C0.5h) after and 7.5 h (C7.5h) after the third dose. In 110 patients during first week of life mean C0.5h was 10.5 mg/l. Mean C0.5h was significantly lower (9.0 mg/l) in 38 infants older than 1 week of age. 14 of 15 patients with Cmin levels > or = 2 mg/l receiving netilmicin every 36 h were < 28 weeks of gestation. In the first week of life significant correlations between GA and elimination half-life (p < 0.001) and between plasma creatinine and elevated Cmin (p < 0.002) were found, but no correlation between C0.5h and GA. In this high-dosage regimen a dosing interval of 48 h for GA < 29 weeks, 36 h for GA 29-36 weeks and 24 h for full term babies seems appropriate, during first week of life, to avoid the majority of elevated trough levels and still obtain maximal therapeutic efficacy. PMID:15307571

  16. 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. PMID:25663270

  17. L'Aventure du LHC

    ScienceCinema

    None

    2011-10-06

    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.

  18. 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.

  19. 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…

  20. 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...

  1. 21 CFR 330.3 - Imprinting of solid oral dosage form drug products.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 5 2014-04-01 2014-04-01 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...

  2. 21 CFR 330.3 - Imprinting of solid oral dosage form drug products.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 5 2012-04-01 2012-04-01 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...

  3. 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...

  4. 21 CFR 330.3 - Imprinting of solid oral dosage form drug products.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 5 2013-04-01 2013-04-01 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...

  5. 21 CFR 524.1580 - Nitrofurazone 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 Nitrofurazone ophthalmic and topical dosage forms... SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS OPHTHALMIC AND TOPICAL DOSAGE FORM NEW ANIMAL DRUGS § 524.1580 Nitrofurazone ophthalmic and topical dosage forms....

  6. 21 CFR 524.660 - Dimethyl sulfoxide 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 Dimethyl sulfoxide ophthalmic and topical dosage... HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS OPHTHALMIC AND TOPICAL DOSAGE FORM NEW ANIMAL DRUGS § 524.660 Dimethyl sulfoxide ophthalmic and topical dosage forms....

  7. 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....

  8. 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... SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS OPHTHALMIC AND TOPICAL DOSAGE FORM NEW ANIMAL DRUGS § 524.1200 Kanamycin ophthalmic and topical dosage forms....

  9. 21 CFR 524.1600 - Nystatin 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 Nystatin ophthalmic and topical dosage forms. 524... SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS OPHTHALMIC AND TOPICAL DOSAGE FORM NEW ANIMAL DRUGS § 524.1600 Nystatin ophthalmic and topical dosage forms....

  10. 21 CFR 524.1484 - Neomycin sulfate 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 Neomycin sulfate ophthalmic and topical dosage... HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS OPHTHALMIC AND TOPICAL DOSAGE FORM NEW ANIMAL DRUGS § 524.1484 Neomycin sulfate ophthalmic and topical dosage forms....

  11. 21 CFR 524.1662 - Oxytetracycline hydrochloride 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 Oxytetracycline hydrochloride ophthalmic and topical dosage forms. 524.1662 Section 524.1662 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF... DOSAGE FORM NEW ANIMAL DRUGS § 524.1662 Oxytetracycline hydrochloride ophthalmic and topical dosage forms....

  12. 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....

  13. 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....

  14. 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....

  15. 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....

  16. 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....

  17. 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... SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.90 Ampicillin implantation and injectible dosage forms....

  18. 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

  19. X-marks the spot: X-chromosome identification during dosage compensation☆

    PubMed Central

    Chery, Jessica; Larschan, Erica

    2016-01-01

    Dosage compensation is the essential process that equalizes the dosage of X-linked genes between the sexes in heterogametic species. Because all of the genes along the length of a single chromosome are co-regulated, dosage compensation serves as a model system for understanding how domains of coordinate gene regulation are established. Dosage compensation has been best studied in mammals, flies and worms. Although dosage compensation systems are seemingly diverse across species, there are key shared principles of nucleation and spreading that are critical for accurate targeting of the dosage compensation complex to the X-chromosome(s). We will highlight the mechanisms by which long non-coding RNAs function together with DNA sequence elements to tether dosage compensation complexes to the X-chromosome. This article is part of a Special Issue entitled: Chromatin and epigenetic regulation of animal development. PMID:24406325

  20. Can we reduce the dosage of biologics in spondyloarthritis?

    PubMed

    Olivieri, Ignazio; D'Angelo, Salvatore; Padula, Angela; Leccese, Pietro; Nigro, Angelo; Palazzi, Carlo

    2013-05-01

    TNF blockers have revolutionized the management of spondyloarthritis (SpA). To date, four anti-TNFα agents (etanercept, infliximab, adalimumab, golimumab) have been approved for the management of ankylosing spondylitis (AS) and psoriatic arthritis (PsA). The first objective in the management of AS and PsA with TNF inhibitors is to reduce disease activity to clinical remission or low disease activity. After remission has been achieved, this state should be maintained as long as possible. However, the financial burden associated with the cost of anti-TNF agents as well as concerns about their long-term safety suggest reducing the dosage of the drug or discontinuing the therapy in the hopes of drug-free remission. The aim of this review is to examine what has, till now, been published on this topic in axial SpA, which includes AS and non-radiographic axial SpA (nr-axSpA), peripheral SpA and PsA. Discontinuation of therapy in axial SpA is not possible in the majority of patients, while on the contrary, reducing the dosage often is. In some patients with peripheral SpA and PsA it is also possible to discontinue therapy and to achieve drug-free remission. PMID:22940233

  1. Gene Dosage Imbalance Contributes to Chromosomal Instability-Induced Tumorigenesis.

    PubMed

    Clemente-Ruiz, Marta; Murillo-Maldonado, Juan M; Benhra, Najate; Barrio, Lara; Pérez, Lidia; Quiroga, Gonzalo; Nebreda, Angel R; Milán, Marco

    2016-02-01

    Chromosomal instability (CIN) is thought to be a source of mutability in cancer. However, CIN often results in aneuploidy, which compromises cell fitness. Here, we used the dosage compensation mechanism (DCM) of Drosophila to demonstrate that chromosome-wide gene dosage imbalance contributes to the deleterious effects of CIN-induced aneuploidy and its pro-tumorigenic action. We present evidence that resetting of the DCM counterbalances the damaging effects caused by CIN-induced changes in X chromosome number. Importantly, interfering with the DCM suffices to mimic the cellular effects of aneuploidy in terms of reactive oxygen species (ROS) production, JNK-dependent cell death, and tumorigenesis upon apoptosis inhibition. We unveil a role of ROS in JNK activation and a variety of cellular and tissue-wide mechanisms that buffer the deleterious effects of CIN, including DNA-damage repair, activation of the p38 pathway, and cytokine induction to promote compensatory proliferation. Our data reveal the existence of robust compensatory mechanisms that counteract CIN-induced cell death and tumorigenesis. PMID:26859353

  2. Maintenance and Loss of Duplicated Genes by Dosage Subfunctionalization.

    PubMed

    Gout, Jean-Francois; Lynch, Michael

    2015-08-01

    Whole-genome duplications (WGDs) have contributed to gene-repertoire enrichment in many eukaryotic lineages. However, most duplicated genes are eventually lost and it is still unclear why some duplicated genes are evolutionary successful whereas others quickly turn to pseudogenes. Here, we show that dosage constraints are major factors opposing post-WGD gene loss in several Paramecium species that share a common ancestral WGD. We propose a model where a majority of WGD-derived duplicates preserve their ancestral function and are retained to produce enough of the proteins performing this same ancestral function. Under this model, the expression level of individual duplicated genes can evolve neutrally as long as they maintain a roughly constant summed expression, and this allows random genetic drift toward uneven contributions of the two copies to total expression. Our analysis suggests that once a high level of imbalance is reached, which can require substantial lengths of time, the copy with the lowest expression level contributes a small enough fraction of the total expression that selection no longer opposes its loss. Extension of our analysis to yeast species sharing a common ancestral WGD yields similar results, suggesting that duplicated-gene retention for dosage constraints followed by divergence in expression level and eventual deterministic gene loss might be a universal feature of post-WGD evolution. PMID:25908670

  3. 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

  4. Evaluation of the dosage of ivermectin in falcons.

    PubMed

    Lierz, M

    2001-05-12

    Twelve groups of falcons, each containing three female gyrfalcon-peregrine falcon hybrids (Falco rusticolus x Falco peregrinus) were injected intramuscularly with a single dose of ivermectin ranging from 0.2 mg/kg to 11 mg/kg bodyweight, and a control group was injected with water. Doses of ivermectin between 0.2 and 5 mg/kg failed to produce clinical signs of illness in the birds. Four birds which received either 6, 7 or 8 mg/kg showed slight clinical signs, and all the birds receiving 9 to 11 mg/kg showed more or less severe clinical signs of anorexia, apathy and sedation. Slight changes in the mean plasma activities of aspartate aminotransferase, alanine aminotransferase and alkaline phosphatase (AP) were detected in the group dosed with 5 mg/kg, and higher dosages caused marked changes in these enzymes as well as in the mean plasma activity of lactate dehydrogenase. The mean activity of AP decreased, and the activities of the other enzymes increased. A dosage of 2 to 3 mg/kg ivermectin is recommended as a safe and effective antiparasitic drug for falcons and it has been used successfully to treat infestations of Serratospiculum species. PMID:11386446

  5. 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. PMID:27194002

  6. 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

  7. Mammalian Y chromosomes retain widely expressed dosage-sensitive regulators

    PubMed Central

    Bellott, Daniel W.; Hughes, Jennifer F.; Skaletsky, Helen; Brown, Laura G.; Pyntikova, Tatyana; Cho, Ting-Jan; Koutseva, Natalia; Zaghlul, Sara; Graves, Tina; Rock, Susie; Kremitzki, Colin; Fulton, Robert S.; Dugan, Shannon; Ding, Yan; Morton, Donna; Khan, Ziad; Lewis, Lora; Buhay, Christian; Wang, Qiaoyan; Watt, Jennifer; Holder, Michael; Lee, Sandy; Nazareth, Lynne; Alföldi, Jessica; Rozen, Steve; Muzny, Donna M.; Warren, Wesley C.; Gibbs, Richard A.; Wilson, Richard K.; Page, David C.

    2014-01-01

    The human X and Y chromosomes evolved from an ordinary pair of autosomes, but millions of years ago genetic decay ravaged the Y chromosome, and only three percent of its ancestral genes survived. We reconstructed the evolution of the Y chromosome across eight mammals to identify biases in gene content and the selective pressures that preserved the surviving ancestral genes. Our findings indicate that survival was non-random, and in two cases, convergent across placental and marsupial mammals. We conclude that the Y chromosome's gene content became specialized through selection to maintain the ancestral dosage of homologous X-Y gene pairs that function as broadly expressed regulators of transcription, translation and protein stability. We propose that beyond its roles in testis determination and spermatogenesis, the Y chromosome is essential for male viability, and plays unappreciated roles in Turner syndrome and in phenotypic differences between the sexes in health and disease. PMID:24759411

  8. Mammalian Y chromosomes retain widely expressed dosage-sensitive regulators.

    PubMed

    Bellott, Daniel W; Hughes, Jennifer F; Skaletsky, Helen; Brown, Laura G; Pyntikova, Tatyana; Cho, Ting-Jan; Koutseva, Natalia; Zaghlul, Sara; Graves, Tina; Rock, Susie; Kremitzki, Colin; Fulton, Robert S; Dugan, Shannon; Ding, Yan; Morton, Donna; Khan, Ziad; Lewis, Lora; Buhay, Christian; Wang, Qiaoyan; Watt, Jennifer; Holder, Michael; Lee, Sandy; Nazareth, Lynne; Alföldi, Jessica; Rozen, Steve; Muzny, Donna M; Warren, Wesley C; Gibbs, Richard A; Wilson, Richard K; Page, David C

    2014-04-24

    The human X and Y chromosomes evolved from an ordinary pair of autosomes, but millions of years ago genetic decay ravaged the Y chromosome, and only three per cent of its ancestral genes survived. We reconstructed the evolution of the Y chromosome across eight mammals to identify biases in gene content and the selective pressures that preserved the surviving ancestral genes. Our findings indicate that survival was nonrandom, and in two cases, convergent across placental and marsupial mammals. We conclude that the gene content of the Y chromosome became specialized through selection to maintain the ancestral dosage of homologous X-Y gene pairs that function as broadly expressed regulators of transcription, translation and protein stability. We propose that beyond its roles in testis determination and spermatogenesis, the Y chromosome is essential for male viability, and has unappreciated roles in Turner's syndrome and in phenotypic differences between the sexes in health and disease. PMID:24759411

  9. Drug dosage in continuous venoveno hemofiltration in critically ill children.

    PubMed

    Assadi, Farahnak; Shahrbaf, Fatemeh Ghane

    2016-01-01

    The dosage of drugs in patients requiring continuous renal replacement therapy need to be adjusted based on a number of variables that that affect pharmacokinetics (PK) including patient weight, CRRT modality (convention, vs. diffusion), blood and/or effluent flow, hemofilter characteristics, physiochemical drug properties, volume of distribution, protein binding and half-life as well as residual renal function. There is a paucity of data on PK studies in children with acute kidney injury requiring CRRT. When possible, therapeutic drug monitoring should be utilized for those medications where serum drug concentrations can be obtained in a clinically relevant time frame. Also, a patient-centered team approach that includes an intensive care unit pharmacist is recommended to prevent medication-related errors and enhance safe and effective medication use is highly recommended. The aim of this article is to review the current guidelines for drug dosing in critically ill children who require continuous venovenous hemofiltration. PMID:26709896

  10. 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. PMID:25899076

  11. Oral Solid Dosage Form Disintegration Testing - The Forgotten Test.

    PubMed

    Al-Gousous, Jozef; Langguth, Peter

    2015-09-01

    Since its inception in the 1930s, disintegration testing has become an important quality control (QC) test in pharmaceutical industry, and disintegration test procedures for various dosage forms have been described by the different pharmacopoeias, with harmonization among them still not quite complete. However, because of the fact that complete disintegration does not necessarily imply complete dissolution, much more research has been focused on dissolution rather than on disintegration testing. Nevertheless, owing to its simplicity, disintegration testing seems to be an attractive replacement to dissolution testing as recognized by the International Conference on Harmonization guidelines, in some cases. Therefore, with proper research being carried out to overcome the associated challenges, the full potential of disintegration testing could be tapped saving considerable efforts allocated to QC testing and quality assurance. PMID:25546430

  12. 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. PMID:10159645

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

    PubMed

    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

  14. 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

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

    PubMed Central

    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. PMID:26550543

  16. Influence of dosage and chemical restraints on feline excretory urography.

    PubMed

    Ajadi, R A; Adetunji, A; Omoerah, V O; Okoh, J U

    2006-12-01

    Three series of trials involving 10 domestic short-haired cats were carried out to determine the influence of dosage of contrast media or type of chemical restraint on feline excretory urography. The 1st series (group A) involved 5 cats sedated with 2.0 mg/kg intramuscular (i.m) injection of 2% xylazine and receiving 800 mg/kg of 76 % meglumine diatrizoate (urografin). The 2nd series (group B) involved another 5 cats sedated with 2.0 mg/kg (i.m) injection of 2% xylazine and receiving 1200 mg/kg of 76% urografin. The 3rd series (group C) involved the repeat urography of the group B cats but sedated with 15 mg/kg (i.m) injection of 5% ketamine hydrochloride. Ventrodorsal radiographs were obtained immediately, 5, 15 and 40 minutes after the injection of 76% urografin. Scores were assigned to nephrographic opacification as described in the literature. The heart rates, respiratory rates and rectal temperatures of the cats were also determined before sedation, after sedation, immediately after the injection of 76% urografin and at 15-minute intervals over a period of 60 minutes. In this study, there were significant differences (P < 0.05) in the nephrographic opacification scores between the group A and group B cats at times 0 and 40 minutes post-administration of urografin. Group A cats had good initial nephrographic opacification which faded later while the nephrographic opacification of group B cats progressively increased. Similarly, nephrographic opacification was significantly (P < 0.05) higher in the xylazine-sedated cats (groups A and B) than the ketamine-sedated cats (group C). However, there were no significant differences (P > 0.05) in heart rates, respiratory rates and rectal temperatures between the 3 groups of cats. It was therefore concluded that increasing the dosage of urografin above 800 mg/kg in cats does not provide additional beneficial effects on the nephrograms produced. Xylazine sedation was observed to produce better nephrographic opacification

  17. 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

  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 524.390 - Chloramphenicol 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 Chloramphenicol ophthalmic and topical dosage forms. 524.390 Section 524.390 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND... NEW ANIMAL DRUGS § 524.390 Chloramphenicol ophthalmic and topical 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 524.981 - Fluocinolone acetonide 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 Fluocinolone acetonide ophthalmic and topical... AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS OPHTHALMIC AND TOPICAL DOSAGE FORM NEW ANIMAL DRUGS § 524.981 Fluocinolone acetonide ophthalmic and topical dosage forms....

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

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 10 Energy 1 2011-01-01 2011-01-01 false Determination of dosages of unsealed byproduct material for medical use. 35.63 Section 35.63 Energy NUCLEAR REGULATORY COMMISSION MEDICAL USE OF BYPRODUCT MATERIAL General Technical Requirements § 35.63 Determination of dosages of unsealed byproduct material for medical use. (a) A licensee shall...

  3. 21 CFR 529.1044 - Gentamicin sulfate in certain other dosage forms.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Gentamicin sulfate in certain other dosage forms. 529.1044 Section 529.1044 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... § 529.1044 Gentamicin sulfate in certain other dosage forms....

  4. 21 CFR 524.1044 - Gentamicin sulfate 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 Gentamicin sulfate ophthalmic and topical dosage forms. 524.1044 Section 524.1044 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND... NEW ANIMAL DRUGS § 524.1044 Gentamicin sulfate ophthalmic and topical dosage forms....

  5. 21 CFR 529.1044 - Gentamicin sulfate in certain other dosage forms.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Gentamicin sulfate in certain other dosage forms. 529.1044 Section 529.1044 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... § 529.1044 Gentamicin sulfate in certain other dosage forms....

  6. 21 CFR 524.1044 - Gentamicin sulfate 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 Gentamicin sulfate ophthalmic and topical dosage forms. 524.1044 Section 524.1044 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND... NEW ANIMAL DRUGS § 524.1044 Gentamicin sulfate ophthalmic and topical dosage forms....

  7. 21 CFR 524.1044 - Gentamicin sulfate 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 Gentamicin sulfate ophthalmic and topical dosage forms. 524.1044 Section 524.1044 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND... NEW ANIMAL DRUGS § 524.1044 Gentamicin sulfate ophthalmic and topical dosage forms....

  8. 21 CFR 529.1044 - Gentamicin in certain other dosage forms.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Gentamicin in certain other dosage forms. 529.1044 Section 529.1044 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Gentamicin in certain other dosage forms....

  9. 21 CFR 524.1044 - Gentamicin sulfate 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 Gentamicin sulfate ophthalmic and topical dosage forms. 524.1044 Section 524.1044 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND... NEW ANIMAL DRUGS § 524.1044 Gentamicin sulfate ophthalmic and topical dosage forms....

  10. 21 CFR 524.1044 - Gentamicin 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 Gentamicin ophthalmic and topical dosage forms. 524.1044 Section 524.1044 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... ANIMAL DRUGS § 524.1044 Gentamicin ophthalmic and topical dosage forms....

  11. 21 CFR 529.1044 - Gentamicin sulfate in certain other dosage forms.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Gentamicin sulfate in certain other dosage forms. 529.1044 Section 529.1044 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... § 529.1044 Gentamicin sulfate in certain other dosage forms....

  12. 21 CFR 529.1044 - Gentamicin sulfate in certain other 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 in certain other dosage forms. 529.1044 Section 529.1044 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... § 529.1044 Gentamicin sulfate in certain other dosage forms....

  13. 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....

  14. 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....

  15. 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....

  16. 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....

  17. 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....

  18. 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...

  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. 21 CFR 524.1881 - Prednisolone acetate 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 Prednisolone acetate ophthalmic and topical dosage forms. 524.1881 Section 524.1881 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND... NEW ANIMAL DRUGS § 524.1881 Prednisolone acetate ophthalmic and topical dosage forms....

  1. 21 CFR 524.1881 - Prednisolone acetate 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 Prednisolone acetate ophthalmic and topical dosage forms. 524.1881 Section 524.1881 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND... NEW ANIMAL DRUGS § 524.1881 Prednisolone acetate ophthalmic and topical dosage forms....

  2. 21 CFR 524.1881 - Prednisolone acetate 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 Prednisolone acetate ophthalmic and topical dosage forms. 524.1881 Section 524.1881 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND... NEW ANIMAL DRUGS § 524.1881 Prednisolone acetate ophthalmic and topical dosage forms....

  3. 21 CFR 524.1881 - Prednisolone acetate 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 Prednisolone acetate ophthalmic and topical dosage forms. 524.1881 Section 524.1881 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND... NEW ANIMAL DRUGS § 524.1881 Prednisolone acetate ophthalmic and topical 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. Spectrophotometric determination of diloxanide furoate in its dosage forms.

    PubMed

    Al-Ghanam, S M; Belal, F

    2001-09-01

    A simple and sensitive spectrophotometric method has been developed for the determination of diloxanide furoate in its dosage forms. The method is based on the reaction of the drug with potassium permanganate in the presence of sodium hydroxide to produce a bluish green coloured species measurable at 610 nm. The absorbance-concentration plot is linear over the range 2.5-20 microg/ml with correlation coefficient (n = 8) of 0.9998 and minimum detectability of 0.2 microg/ml (6.1 x 10(-7) M). The molar absorptivity was 1.1 x 10(4) l/mol cm. The different experimental parameters affecting the development and stability of the colour were carefully studied and optimised. The proposed method was applied successfully for the determination of diloxanide furoate in its tablet form. The results obtained were in good agreement with those obtained using the official method. The proposed method could be applied to the determination of diloxanide furoate in presence of some co-formulated drugs. The effect of sensitisers and surfactants on the performance of the proposed method was also studied. A proposal of the reaction pathway was presented. PMID:11680811

  6. An interface model for dosage adjustment connects hematotoxicity to pharmacokinetics.

    PubMed

    Meille, C; Iliadis, A; Barbolosi, D; Frances, N; Freyer, G

    2008-12-01

    When modeling is required to describe pharmacokinetics and pharmacodynamics simultaneously, it is difficult to link time-concentration profiles and drug effects. When patients are under chemotherapy, despite the huge amount of blood monitoring numerations, there is a lack of exposure variables to describe hematotoxicity linked with the circulating drug blood levels. We developed an interface model that transforms circulating pharmacokinetic concentrations to adequate exposures, destined to be inputs of the pharmacodynamic process. The model is materialized by a nonlinear differential equation involving three parameters. The relevance of the interface model for dosage adjustment is illustrated by numerous simulations. In particular, the interface model is incorporated into a complex system including pharmacokinetics and neutropenia induced by docetaxel and by cisplatin. Emphasis is placed on the sensitivity of neutropenia with respect to the variations of the drug amount. This complex system including pharmacokinetic, interface, and pharmacodynamic hematotoxicity models is an interesting tool for analysis of hematotoxicity induced by anticancer agents. The model could be a new basis for further improvements aimed at incorporating new experimental features. PMID:19107581

  7. [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. PMID:25747220

  8. 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. PMID:21802501

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

    PubMed

    Łaszcz, Marta; Witkowska, Anna

    2016-01-01

    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. PMID:26397209

  10. Carboxymethyl starch mucoadhesive microspheres as gastroretentive dosage form.

    PubMed

    Lemieux, Marc; Gosselin, Patrick; Mateescu, Mircea Alexandru

    2015-12-30

    Carboxymethyl starch microspheres (CMS-MS) were produced from carboxymethyl starch powder (CMS-P) with a degree of substitution (DS) from 0.1 to 1.5 in order to investigate the influence of DS on physicochemical, drug release and mucoadhesion properties as well as interactions with gastrointestinal tract (GIT) epithelial barrier models. Placebo and furosemide loaded CMS-MS were obtained by emulsion-crosslinking with sodium trimetaphosphate (STMP). DS had an impact on increasing equilibrium water uptake and modulating drug release properties of the CMS-MS according to the surrounding pH. The transepithelial electrical resistance (TEER) of NCI-N87 gastric cell monolayers was not influenced in presence of CMS-MS, whereas that of Caco-2 intestinal cell monolayers decreased with increasing DS but recovered initial values at about 15h post-treatment. CMS-MS with increasing DS also enhanced furosemide permeability across both NCI-N87 and Caco-2 monolayers at pH gradients from 3.0 to 7.4. Mucoadhesion of CMS-MS on gastric mucosa (acidic condition) increased with the DS up to 55% for a DS of 1.0 but decreased on neutral intestinal mucosa to less than 10% with DS of 0.1. The drug release, permeability enhancement and mucoadhesive properties of the CMS-MS suggest CMS-MS with DS between 0.6 and 1.0 as suitable excipient for gastroretentive oral delivery dosage forms. PMID:26456246

  11. 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. PMID:27273510

  12. 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. PMID:26952879

  13. Sample sizes in dosage investigational clinical trials: a systematic evaluation.

    PubMed

    Huang, Ji-Han; Su, Qian-Min; Yang, Juan; Lv, Ying-Hua; He, Ying-Chun; Chen, Jun-Chao; Xu, Ling; Wang, Kun; Zheng, Qing-Shan

    2015-01-01

    The main purpose of investigational phase II clinical trials is to explore indications and effective doses. However, as yet, there is no clear rule and no related published literature about the precise suitable sample sizes to be used in phase II clinical trials. To explore this, we searched for clinical trials in the ClinicalTrials.gov registry using the keywords "dose-finding" or "dose-response" and "Phase II". The time span of the search was September 20, 1999, to December 31, 2013. A total of 2103 clinical trials were finally included in our review. Regarding sample sizes, 1,156 clinical trials had <40 participants in each group, accounting for 55.0% of the studies reviewed, and only 17.2% of the studies reviewed had >100 patient cases in a single group. Sample sizes used in parallel study designs tended to be larger than those of crossover designs (median sample size 151 and 37, respectively). In conclusion, in the earlier phases of drug research and development, there are a variety of designs for dosage investigational studies. The sample size of each trial should be comprehensively considered and selected according to the study design and purpose. PMID:25609916

  14. Photopatch test reactivity: effect of photoallergen concentration and UVA dosaging.

    PubMed

    Hasan, T; Jansen, C T

    1996-06-01

    We have studied the influence of variations in allergen concentration and UVA dosaging on the results of photopatch testing with the Scandinavian standard photopatch series in 29 patients with photocontact and/or contact allergy to 1 or several of the allergens in that series. Photocontact test reactions were more sensitive to allergen dilution than plain contact test reactions. Even dilution from the standard 5% to 2.5% significantly reduced para-aminobenzoic acid photocontact test reactions. Reducing the UVA dose from the standard 5 J/cm2 to 2.5 or 1 J/cm2 in 2 out of 5 cases turned a significant (++) reaction into a doubtful one (+). Increasing the standard UVA dose of 5 J/ cm2 to 20-40 J/cm2 turned a single + photocontact reaction to trichlorcarbanilide and a single 1 + plain contact reaction to chlorhexidine into ++ reactions. In the majority of cases, however, neither photocontact nor plain contact test reactions were augemented by UVA doses up to 80 J/cm2. We conclude that a UVA dose of 5 J/cm2 is sufficient for eliciting photocontact allergic test reactions, and that a reduction of either the UVA dose level or the standard allergen concentrations of the Scandinavian photopatch test guidelines may cause loss of significant photocontact test reactions in a proportion of the cases. PMID:8879921

  15. 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.

  16. Calculator programs to deal with non-steady state, multiple dosage regimen clinical pharmacokinetics.

    PubMed

    Ensom, R J; Nakagawa, R S

    1983-07-01

    Serum drug levels have become a useful tool in the optimization of dosage requirements for several therapeutically important drugs. In the acute care situation the interpretation of these levels is complicated by multiple dosage regimens and inadequate time to achieve steady-state serum drug levels. Mathematical equations describing first order single compartment pharmacokinetics have been compiled. An alpha-numeric programmable calculator has been programmed to accept information regarding up to seven different serial dosage regimens. The calculator is also programmed to predict concentrations at any time during a complex set of dosage regimens or peak, trough, and average concentrations given a maintenance dosage regimen. Examples are given to demonstrate the usefulness of the programs in the clinical setting. PMID:6688607

  17. 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

  18. Evolution of dosage compensation under sexual selection differs between X and Z chromosomes

    PubMed Central

    Mullon, Charles; Wright, Alison E.; Reuter, Max; Pomiankowski, Andrew; Mank, Judith E.

    2015-01-01

    Complete sex chromosome dosage compensation has more often been observed in XY than ZW species. In this study, using a population genetic model and the chicken transcriptome, we assess whether sexual conflict can account for this difference. Sexual conflict over expression is inevitable when mutation effects are correlated across the sexes, as compensatory mutations in the heterogametic sex lead to hyperexpression in the homogametic sex. Coupled with stronger selection and greater reproductive variance in males, this results in slower and less complete evolution of Z compared with X dosage compensation. Using expression variance as a measure of selection strength, we find that, as predicted by the model, dosage compensation in the chicken is most pronounced in genes that are under strong selection biased towards females. Our study explains the pattern of weak dosage compensation in ZW systems, and suggests that sexual selection plays a major role in shaping sex chromosome dosage compensation. PMID:26212613

  19. The shaping and functional consequences of the dosage effect landscape in multiple myeloma

    PubMed Central

    2013-01-01

    Background Multiple myeloma (MM) is a malignant proliferation of plasma B cells. Based on recurrent aneuploidy such as copy number alterations (CNAs), myeloma is divided into two subtypes with different CNA patterns and patient survival outcomes. How aneuploidy events arise, and whether they contribute to cancer cell evolution are actively studied. The large amount of transcriptomic changes resultant of CNAs (dosage effect) pose big challenges for identifying functional consequences of CNAs in myeloma in terms of specific driver genes and pathways. In this study, we hypothesize that gene-wise dosage effect varies as a result from complex regulatory networks that translate the impact of CNAs to gene expression, and studying this variation can provide insights into functional effects of CNAs. Results We propose gene-wise dosage effect score and genome-wide karyotype plot as tools to measure and visualize concordant copy number and expression changes across cancer samples. We find that dosage effect in myeloma is widespread yet variable, and it is correlated with gene expression level and CNA frequencies in different chromosomes. Our analysis suggests that despite the enrichment of differentially expressed genes between hyperdiploid MM and non-hyperdiploid MM in the trisomy chromosomes, the chromosomal proportion of dosage sensitive genes is higher in the non-trisomy chromosomes. Dosage-sensitive genes are enriched by genes with protein translation and localization functions, and dosage resistant genes are enriched by apoptosis genes. These results point to future studies on differential dosage sensitivity and resistance of pro- and anti-proliferation pathways and their variation across patients as therapeutic targets and prognosis markers. Conclusions Our findings support the hypothesis that recurrent CNAs in myeloma are selected by their functional consequences. The novel dosage effect score defined in this work will facilitate integration of copy number and

  20. 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

  1. COX-2 gene dosage-dependent defects in kidney development.

    PubMed

    Slattery, Patrick; Frölich, Stefanie; Schreiber, Yannik; Nüsing, Rolf M

    2016-05-15

    Deletion of cyclooxygenase (COX)-2 causes impairment of kidney development, including hypothrophic glomeruli and cortical thinning. A critical role for COX-2 is seen 4-8 days postnatally. The present study was aimed at answering whether different COX-2 gene dosage and partial pharmacological COX-2 inhibition impairs kidney development. We studied kidney development in COX-2(+/+), COX-2(+/-), and COX-2(-/-) mice as well as in C57Bl6 mice treated postnatally with low (5 mg·kg(-1)·day(-1)) and high (10 mg·kg(-1)·day(-1)) doses of the selective COX-2 inhibitor SC-236. COX-2(+/-) mice exhibit impaired kidney development leading to reduced glomerular size but, in contrast to COX-2(-/-) mice, only marginal cortical thinning. Moreover, in COX-2(+/-) and COX-2(-/-) kidneys, juxtamedullary glomeruli, which develop in the very early stages of nephrogenesis, also showed a size reduction. In COX-2(+/-) kidneys at the age of 8 days, we observed significantly less expression of COX-2 mRNA and protein and less PGE2 and PGI2 synthetic activity compared with COX-2(+/+) kidneys. The renal defects in COX-2(-/-) and COX-2(+/-) kidneys could be mimicked by high and low doses of SC-236, respectively. In aged COX-2(+/-) kidneys, glomerulosclerosis was observed; however, in contrast to COX-2(-/-) kidneys, periglomerular fibrosis was absent. COX-2(+/-) mice showed signs of kidney insufficiency, demonstrated by enhanced serum creatinine levels, quite similar to COX-2(-/-) mice, but, in contrast, serum urea remained at the control level. In summary, function of both COX-2 gene alleles is absolutely necessary to ensure physiological development of the mouse kidney. Loss of one copy of the COX-2 gene or partial COX-2 inhibition is associated with distinct renal damage and reduced kidney function. PMID:26984955

  2. The importance of MDR1 gene polymorphisms for tacrolimus dosage.

    PubMed

    Kravljaca, Milica; Perovic, Vladimir; Pravica, Vera; Brkovic, Voin; Milinkovic, Marija; Lausevic, Mirjana; Naumovic, Radomir

    2016-02-15

    Polymorphisms of the multi drug resistance (MDR1) gene cause variability in P-glycoprotein mediated metabolism of tacrolimus. The aim of this study was to examine the relationship between MDR1 gene single nucleotide polymorphisms (SNPs) and their haplotypes with dosage of tacrolimus in kidney transplant recipients who were cytochrome (CYP) 3A5*3 homozygotes. This study included 91 kidney transplant recipients followed two years after transplantation. Detection and analysis of MDR1 gene polymorphisms in positions C1236T, G2677T/A and C3435T were performed using PCR method. Patients with variant alleles for SNPs G2677T/A and C3435T required higher doses of tacrolimus and had a lower level/dose (L/D) ratio than patients with wild alleles or heterozygotes. That difference was the most obvious for SNP G2677T/A where TT homozygotes required significantly higher doses of tacrolimus during whole follow-up. Their L/D was significantly lower in the first month after transplantation. Recipients with CTT/TTT haplotype also had lower L/D than those with CGC/TTT and CGC/CGC, significantly in the 10th and 20th days after transplantation respectively (p<0.05). Our results demonstrate that TT homozygotes at positions G2677T/A and C3435T required a higher tacrolimus dose than those with wild alleles or heterozygotes. It may be helpful in the prevention of tacrolimus nephrotoxicity early after transplantation. PMID:26705892

  3. Bioavailability of medroxyprogesterone acetate from three oral dosage formulations.

    PubMed

    Stalker, D J; Welshman, I R; Pollock, S R

    1992-01-01

    The bioavailability of three formulations of medroxyprogesterone acetate (MPA) was assessed in 30 healthy male volunteers in a three-way, open-label, cross-over-designed trial. Each subject received one Provera 500-mg tablet, one Farlutal 500-mg tablet, and one Provera 500-mg granule packet according to a randomized schedule, with each treatment separated by a 21-day washout period. Serum MPA levels were determined using both radioimmunoassay (RIA) and high-performance liquid chromatography techniques. Based on the results of RIA analysis, Farlutal tablets produced significantly lower serum MPA concentrations compared with Provera tablets at most sampling times, resulting in statistically lower AUC0-144 for the Farlutal tablet (544 vs 768 ng.hr/ml; -29.2%). The Farlutal tablet also had a significantly lower maximum concentration than the Provera tablet (27.8 vs 47.4 ng/ml; -41.4%). However, there was no significant difference in time of maximum concentration between the tablet formulations (3.71 vs 3.41 hr), indicating that the rates of absorption of the two tablet formulations were comparable. Provera granules provided significantly higher serum MPA levels than Provera tablets at 0.5, 1, 1.5, 2, and 6 hours, and the AUC0-144 for Provera granules was higher by 5.47% (810 vs 768 ng.hr/ml). There were no differences in terminal elimination rate constants among the dosage forms. No significant adverse events were noted during the trial. The relative bioavailabilities of Provera granules and Farlutal tablets were 105% and 71.2%, respectively, compared with Provera tablets. PMID:1388093

  4. Cystic gene dosage influences kidney lesions after nephron reduction.

    PubMed

    Le Corre, Stéphanie; Viau, Amandine; Burtin, Martine; El-Karoui, Khalil; Cnops, Yvette; Terryn, Sara; Debaix, Huguette; Bérissi, Sophie; Gubler, Marie-Claire; Devuyst, Olivier; Terzi, Fabiola

    2015-01-01

    Cystic kidney disease is characterized by the progressive development of multiple fluid-filled cysts. Cysts can be acquired, or they may appear during development or in postnatal life due to specific gene defects and lead to renal failure. The most frequent form of this disease is the inherited polycystic kidney disease (PKD). Experimental models of PKD showed that an increase of cellular proliferation and apoptosis as well as defects in apico-basal and planar cell polarity or cilia play a critical role in cyst development. However, little is known about the mechanisms and the mediators involved in acquired cystic kidney diseases (ACKD). In this study, we used the nephron reduction as a model to study the mechanisms underlying cyst development in ACKD. We found that tubular dilations after nephron reduction recapitulated most of the morphological features of ACKD. The development of tubular dilations was associated with a dramatic increase of cell proliferation. In contrast, the apico-basal polarity and cilia did not seem to be affected. Interestingly, polycystin 1 and fibrocystin were markedly increased and polycystin 2 was decreased in cells lining the dilated tubules, whereas the expression of several other cystic genes did not change. More importantly, Pkd1 haploinsufficiency accelerated the development of tubular dilations after nephron reduction, a phenotype that was associated to a further increase of cell proliferation. These data were relevant to humans ACKD, as cystic genes expression and the rate of cell proliferation were also increased. In conclusion, our study suggests that the nephron reduction can be considered a suitable model to study ACKD and that dosage of genes involved in PKD is also important in ACKD. PMID:25531116

  5. 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 ...

  6. 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. PMID:11186141

  7. Dosage Effects of a Drosophila Sodium Channel Gene on Behavior and Axonal Excitability

    PubMed Central

    Stern, M.; Kreber, R.; Ganetzky, B.

    1990-01-01

    The effects of para mutations on behavior and axonal excitability in Drosophila suggested that para specifically affects sodium channels. This hypothesis was confirmed by molecular analysis of the para locus, which demonstrates that the encoded para product is a sodium channel polypeptide. Here we characterize the effects of altered para(+) dosage on behavior and axonal excitability, both in an otherwise wild-type background and in combination with two other mutations: nap(ts), which also affects sodium channels, and Sh(KS133), which specifically affects potassium channels. Whereas it was previously shown that decreased dosage of para(+) is unconditionally lethal in a .nap(ts) background, we find that increased dosage of para(+) suppresses nap(ts). Similarly, we find that para hypomorphs or decreased dosage of para(+) suppresses Sh(KS133), whereas increased dosage of para(+) enhances Sh(KS133). The electrophysiological basis for these effects is investigated. Other genes in Drosophila that have sequence homology to sodium channels do not show such dosage effects, which suggests that the para(+) product has a function distinct from that of other putative Drosophila sodium channel genes. We conclude that the number of sodium channels present in at least some Drosophila neurons can be affected by changes in para(+) gene dosage, and that the level of para(+) expression can strongly influence neuronal excitability. PMID:2155153

  8. Stability considerations in liquid dosage forms extemporaneously prepared from commercially available products.

    PubMed

    Glass, Beverley D; Haywood, Alison

    2006-01-01

    The pharmacist, both in community and hospital pharmacy practice, is often challenged with the preparation of a liquid dosage form not available commercially for paediatric patients, those adults unable to swallow tablets or capsules and patients who must receive medications via nasogastric or gastrostomy tubes. Recognising the lack of information available to healthcare professionals, a general discussion of the various parameters that may be modified in preparing these dosage forms and a tabulated summary of the dosage forms presented in the literature is described, which, although not exhaustive, will provide information on the formulation and stability of the most commonly prepared extemporaneous liquid dosage forms. An extensive survey of the literature and investigation of 83 liquid dosage forms revealed that stability considerations were of concern for only 7.2% of these liquid dosage forms, extemporaneously prepared from the following commercially available products: captopril, hydralazine hydrochloride, isoniazid, levothyroxine sodium, phenoxybenzamine hydrochloride and tetracycline hydrochloride. Inclusion of the antioxidant, sodium ascorbate in the liquid dosage form for captopril resulted in improved stability at 4 degrees C. Hydralazine hydrochloride, isoniazid and phenoxybenzamine hydrochloride were adversely affected due to interactions with excipients in the formulation, while the effect of the preservative in lowering the pH in a levothyroxine sodium mixture resulted in decreased stability. Interestingly, the instability in these formulations is primarily due to interactions between the drug substance and the excipients rather than degradation of the active pharmaceutical ingredient by standard routes such as oxidation, hydrolysis, photolysis or thermolysis. This low percentage however illustrates the low risk associated with these dosage forms investigated. It may be concluded that when considering the safety and efficacy of liquid dosage forms

  9. 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

  10. Conservation and de novo acquisition of dosage compensation on newly evolved sex chromosomes in Drosophila

    PubMed Central

    Alekseyenko, Artyom A.; Ellison, Christopher E.; Gorchakov, Andrey A.; Zhou, Qi; Kaiser, Vera B.; Toda, Nick; Walton, Zaak; Peng, Shouyong; Park, Peter J.; Bachtrog, Doris; Kuroda, Mitzi I.

    2013-01-01

    Dosage compensation has arisen in response to the evolution of distinct male (XY) and female (XX) karyotypes. In Drosophila melanogaster, the MSL complex increases male X transcription approximately twofold. X-specific targeting is thought to occur through sequence-dependent binding to chromatin entry sites (CESs), followed by spreading in cis to active genes. We tested this model by asking how newly evolving sex chromosome arms in Drosophila miranda acquired dosage compensation. We found evidence for the creation of new CESs, with the analogous sequence and spacing as in D. melanogaster, providing strong support for the spreading model in the establishment of dosage compensation. PMID:23630075

  11. Pru du 2S albumin or Pru du vicilin?

    PubMed

    Garino, Cristiano; De Paolis, Angelo; Coïsson, Jean Daniel; Arlorio, Marco

    2015-06-01

    A short partial sequence of 28 amino acids is all the information we have so far about the putative allergen 2S albumin from almond. The aim of this work was to analyze this information using mainly bioinformatics tools, in order to verify its rightness. Based on the results reported in the paper describing this allergen from almond, we analyzed the original data of amino acids sequencing through available software. The degree of homology of the almond 12kDa protein with any other known 2S albumin appears to be much lower than the one reported in the paper that firstly described it. In a publicly available cDNA library we discovered an expressed sequence tag which translation generates a protein that perfectly matches both of the sequencing outputs described in the same paper. A further analysis indicated that the latter protein seems to belong to the vicilin superfamily rather than to the prolamin one. The fact that also vicilins are seed storage proteins known to be highly allergenic would explain the IgE reactivity originally observed. Based on our observations we suggest that the IgE reactive 12kDa protein from almond currently known as Pru du 2S albumin is in reality the cleaved N-terminal region of a 7S vicilin like protein. PMID:25854802

  12. 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

  13. 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. PMID:19647461

  14. 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. PMID:25945861

  15. 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. PMID:26323428

  16. Dosage compensation and nuclear organization: cluster to control chromosome-wide gene expression.

    PubMed

    Sharma, Rahul; Meister, Peter

    2016-04-01

    In many species, male and female animals differ in the number of X chromosomes they possess. As a consequence, large scale differences in gene dosage exist between sexes; a phenomenon that is rarely tolerated by the organism for changes in autosome dosage. Several strategies have evolved independently to balance X-linked gene dosage between sexes, named dosage compensation (DC). The molecular basis of DC differs among the three best-studied examples: mammals, fruit fly and nematodes. In this short review, we summarize recent microscopic and chromosome conformation capture data that reveal key features of the compensated X chromosome and highlight the events leading to the establishment of a functional, specialized nuclear compartment, the X domain. PMID:26748388

  17. A comparative study of two dosage levels of ibuprofen syrup in children with pyrexia.

    PubMed

    Kotob, A

    1985-01-01

    In a study of the antipyretic effect of two dosage levels of ibuprofen syrup in children with fever due to a variety of causes, forty-four out of the fifty children admitted completed the 24-hour trial period, twenty-three receiving 20 mg ibuprofen/kg body-weight, twenty-one receiving 30 mg/kg ibuprofen. Both dosage levels gave highly significant (p less than 0.001) reductions in rectal temperatures, with a statistically significant reduction, at the 5% level, in favour of the higher dose at 12 and 20 hours. No side-effects were reported at either dosage level, and the taste was acceptable to all the children. It is concluded that ibuprofen was a useful and effective antipyretic drug in the population studied, and that the higher dosage is preferable to the lower, being more effective, equally palatable, and giving rise to no side-effects in this study. PMID:3888726

  18. Plasma levels of clobazam after three oral dosage forms in health subjects.

    PubMed

    Vallner, J J; Needham, T E; Jun, H W; Brown, W J; Stewart, J T; Kotzan, J A; Honigberg, I L

    1978-07-01

    As can be seen from the tables, the terminal half-life of clobazam is about 50 hours, and from a solid dosage form the peak plasma level occurs approximately 1.5 hours after ingestion. Thus, there is a significant, yet relatively short, dosage form delay effect when the solid dosage forms are compared to the rapidly available solution of the drug. However, based on the areas under the curve, comparison of the solid dosage forms with the solution indicates that the fraction of clobazam absorbed is 1. Pupil diameter measurement at 2, 4, and 6 hours after ingestion of clobazam correlated well with the plasma levels at these times. Pupils were constricted to the highest degree at 2 hours and approached the initial pupillary diameter at the 6-hour measurement. PMID:27537

  19. 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

  20. 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.

  1. Genetics-Based Pediatric Warfarin Dosage Regimen Derived Using Pharmacometric Bridging

    PubMed Central

    Lala, Mallika; Burckart, Gilbert J.; Takao, Cheryl M.; Pravica, Vera; Momper, Jeremiah D.; Gobburu, Jogarao V.S.

    2013-01-01

    BACKGROUND Warfarin dosage regimens using CYP2C9 and VKORC1 polymorphisms have been extensively studied in adults and is included in US Food and Drug Administration-approved warfarin labeling. However, no dosage algorithm is available for pediatric patients. OBJECTIVE To derive a genetics-based pediatric dosge regimen for warfarin, including starting dose and titration scheme. METHODS A model-based approach was developed based on a previously validated warfarin dosage model in adults, with subsequent comparison to pediatric data from pediatric warfarin dose, genotyping, and international normalized ratio (INR) results. The adult model was based on a previously established model from the CROWN (CReating an Optimal Warfarin dosing Nomogram) trial. Pediatric warfarin data were obtained from a study conducted at the Children’s Hospital of Los Angeles with 26 subjects. Variant alleles of CYP2C9 (rs1799853 or *2, and rs1057910 or *3) and the VKORC1 single nucleotide polymorphism (SNP) rs9923231 (−1639 G>A) were assessed, where the rs numbers are reference SNP identification tags assigned by the National Center for Biotechnology Information. RESULTS A pediatric warfarin model was derived using the previously validated model and clinical pharmacology considerations. The model was validated, and clinical trial simulation and stochastic modeling were used to optimize pediatric dosage and titration. The final dosage regimen was optimized based on simulations targeting a high (≥60%) proportion of INRs within the therapeutic range by week 2 of warfarin therapy while minimizing INRs >3.5 or <2. CONCLUSIONS The proposed pediatric warfarin dosage scheme based on individual CYP2C9 (alleles *1,*2,*3) and VKORC1 rs9923231 (-1639 G>A) genotypes may offer improved dosage compared to current treatment strategies, especially in patients with variant CYP2C9 and VKORC1 alleles. This pilot study provides the foundation for a larger prospective evaluation of genetics-based warfarin

  2. Complete Dosage Compensation and Sex-Biased Gene Expression in the Moth Manduca sexta

    PubMed Central

    Smith, Gilbert; Chen, Yun-Ru; Blissard, Gary W.; Briscoe, Adriana D.

    2014-01-01

    Sex chromosome dosage compensation balances homogametic sex chromosome expression with autosomal expression in the heterogametic sex, leading to sex chromosome expression parity between the sexes. If compensation is incomplete, this can lead to expression imbalance and sex-biased gene expression. Recent work has uncovered an intriguing and variable pattern of dosage compensation across species that includes a lack of complete dosage compensation in ZW species compared with XY species. This has led to the hypothesis that ZW species do not require complete compensation or that complete compensation would negatively affect their fitness. To date, only one study, a study of the moth Bombyx mori, has discovered evidence for complete dosage compensation in a ZW species. We examined another moth species, Manduca sexta, using high-throughput sequencing to survey gene expression in the head tissue of males and females. We found dosage compensation to be complete in M. sexta with average expression between the Z chromosome in males and females being equal. When genes expressed at very low levels are removed by filtering, we found that average autosome expression was highly similar to average Z expression, suggesting that the majority of genes in M. sexta are completely dosage compensated. Further, this compensation was accompanied by sex-specific gene expression associated with important sexually dimorphic traits. We suggest that complete dosage compensation in ZW species might be more common than previously appreciated and linked to additional selective processes, such as sexual selection. More ZW and lepidopteran species should now be examined in a phylogenetic framework, to understand the evolution of dosage compensation. PMID:24558255

  3. 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

  4. 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. PMID:26519856

  5. 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. PMID:9566150

  6. 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. PMID:27261752

  7. Genome-wide association analysis to predict optimal antipsychotic dosage in schizophrenia: a pilot study.

    PubMed

    Koga, Arthur T; Strauss, John; Zai, Clement; Remington, Gary; De Luca, Vincenzo

    2016-03-01

    In recent years, several studies have investigated genetic polymorphisms of antipsychotic drug-metabolizing enzymes and receptors. However, most studies focused on drug response and very few have investigated the genetic influence on antipsychotic dosage. The aim of the present study is to test the association between antipsychotic dosages at genome-wide level. The current dosage of antipsychotic medications was collected from 79 schizophrenia patients. The dosage was standardized using three different methods: chlorpromazine equivalent (CPZe), defined daily dose (DDD), and percentage of maximum dose (PM %). The patients were then genotyped using the Illumina HumanOmni2.5-8 BeadChip Kit. All markers were screened for significance using linear regression, and the p values were visualized using a Manhattan plot. The genome-wide analysis showed that the top Single-Nucleotide Polymorphisms (SNPs) associated with dosage variation were rs981975 on chromosome 14 for CPZe, rs4470690 on chromosome 4 for PM %, and rs79323383 on chromosome 8 for DDD. However, no genome-wide significantly associated SNPs were identified. In this pilot sample, we found promising trends for pharmacodynamic targets associated with antipsychotic dosage. Therefore, studies combining large prescription databases may identify genetic predictors to adjust the dose of antipsychotic medication. PMID:26821981

  8. Genes and Small RNA Transcripts Exhibit Dosage-Dependent Expression Pattern in Maize Copy-Number Alterations.

    PubMed

    Zuo, Tao; Zhang, Jianbo; Lithio, Andrew; Dash, Sudhansu; Weber, David F; Wise, Roger; Nettleton, Dan; Peterson, Thomas

    2016-07-01

    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 which tend to be dosage compensated. In plants, genes within small duplications (<100 kb) often exhibit dosage-dependent expression, whereas large duplications (>50 Mb) are more often dosage compensated. However, little or nothing is known about expression in moderately-sized (1-50 Mb) segmental duplications, and about the response of small RNAs to dosage change. Here, we compared maize (Zea mays) plants with two, three, and four doses of a 14.6-Mb segment of chromosome 1 that contains ∼300 genes. Plants containing the duplicated segment exhibit dosage-dependent effects on ear length and flowering time. Transcriptome analyses using GeneChip and RNA-sequencing methods indicate that most expressed genes and unique small RNAs within the duplicated segments exhibit dosage-dependent transcript levels. We conclude that dosage effect is the predominant regulatory response for both genes and unique small RNA transcripts in the segmental dosage series we tested. To our knowledge this is the first analysis of small RNA expression in plant gene dosage variants. Because segmental duplications comprise a significant proportion of eukaryotic genomes, these findings provide important new insight into the regulation of genes and small RNAs in response to dosage changes. PMID:27129738

  9. Résultats du traitement du synovialosarcome des members

    PubMed Central

    Lukulunga, Loubet Unyendje; Moussa, Abdou Kadri; Mahfoud, Mustapha; El Bardouni, Ahmed; Ismail, Farid; Kharmaz, Mohammed; Berrada, Mohamed Saleh; El Yaacoubi, Moradh

    2014-01-01

    Les synovialosarcomes, sarcomes de haut grade, sont de diagnostic tardif et le traitement est complexe et onéreux, nécessitant la mise en œuvre d'une équipe pluridisciplinaire. Le but de ce travail était d'apprécier les résultats de l'association de la chirurgie à la radio chimiothérapie des synovialosarcomes des membres. Il s'agissait d'une étude rétrospective portant sur des patients présentant de synovialosarcomes des membres pris en charge dans le service de chirurgie orthopédique et traumatologique du CHU Ibn SINA de Rabat allant de Janvier 2006 à Décembre 2011 (6 ans). Nous avons inclus les malades présentant de synovialosarcomes des membres dont la clinique et l'imagerie médicale étaient en faveur, confirmés par l'examen anatomopathologique et la prise en charge effectuée dans le service. Les patients ont été revus avec un recul moyen de 3 ans. Nous n'avons pas retenu les patients dont les dossiers étaient incomplets, perdus de vue. Nous avons apprécié les résultats selon les critères carcinologiques et le score MSTS (Musculoskeletal Tumor Society). La saisie et l'analyse des données ont été faites sur le logiciel SPSS Stastic 17.0 Nous avons colligé 20 cas de synovialosarcome des membres dans le Service de Chirurgie Orthopédique et Traumatologique au CHU Ibn SINA de Rabat Le sexe masculin a prédominé avec 65% (n = 13) avec un sex ratio 1,85. L’âge moyen a été de 42,6 ans avec des extrêmes allant de 20 ans et 70 ans. Notre délai moyen de consultation était de 14,42 mois. Tous les malades ont consulté pour une tuméfaction dans 100% (localisée au membre inférieur dans 65% (n = 13), membre supérieur dans 35% (n = 7). La douleur était associée à la tuméfaction dans 55% (n = 11), quant à l'altération de l’état général et l'ulcération de la masse, elles ont été notées dans 3 cas chacune. Nous avons réalisé un bilan d'imagerie médicale comprenant: radiographie standard, échographie, écho doppler

  10. 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.

  11. 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. PMID:27178343

  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. [Some problems for dosage form based on questionnaire surveying compliance in patients taking tamsulosin hydrochloride].

    PubMed

    Ogata, Ikuko; Yamasaki, Keishi; Tsuruda, Atsuko; Tsuzaki, Shoichiro; Ishimatsu, Takashi; Hirayama, Hideo; Seo, Hakaru

    2008-02-01

    After the dosage form of tamsulosin hydrochloride was changed from a capsule to on orally disintegrating tablet (ODT, Harnal D), we often received patient complaints and noted an increase in noncompliance with medication regimens. The change in dosage form appeared to cause poor compliance by patients who had become accustomed to the light pink/white capsule over many years. Therefore, we carried out a questionnaire survey of patients taking the ODT form to determine the effects of changing the dosage form and the usefulness of the ODT. Most (92%) of respondents took the ODT with water. In addition, 16% missed taking the medicine after the change in dosage form. ODT is a dosage form that is easy to take for patient with dysphagia, or those on restricted water intake. However, it appears that elderly men and patients with visual disorders cannot distinguish the ODT from other medicines and this affects patient compliance. In conclusion, all pharmaceutical companies should consider the design of medications in terms of coloration, indications, or shape in anticipation of the aging society in future, so that patients can distinguish them. Furthermore, sufficient pharmaceutical care is needed to improve both compliance and safety management for the elderly. PMID:18239377

  14. 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. PMID:26240990

  15. Characterization of drug efficacy regions based on dosage and frequency schedules.

    PubMed

    Li, Xiangfang Lindsey; Qian, Lijun; Bittner, Michael L; Dougherty, Edward R

    2011-03-01

    This paper proposes a framework to study the drug effect at the molecular level in order to address the following question of current interest in the drug community: Given a fixed total delivered drug, which is better, frequent small or infrequent large drug dosages? A hybrid system model is proposed to link the drug's pharmacokinetic and pharmacodynamic information, and allows the drug effects for different dosages and treatment schedules to be compared. A hybrid model facilitates the modeling of continuous quantitative changes that leads to discrete transitions. An optimal dosage-frequency regimen and the necessary and sufficient conditions for the drug to be effective are obtained analytically when the drug is designed to control a target gene. Then, we extend the analysis to the case where the target gene is part of a genetic regulatory network. A crucial observation is that there exists a "sweet spot," defined as the "drug efficacy region (DER)" in this paper, for certain dosage and frequency arrangements given the total delivered drug. This paper quantifies the therapeutic benefits of dosage regimen lying within the DER. Simulations are performed using MATLAB/SIMULINK to validate the analytical results. PMID:21095860

  16. 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…

  17. 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…

  18. 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.

  19. 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. PMID:26523769

  20. Dosage Compensation in DROSOPHILA MELANOGASTER Triploids. II. Glucose-6-Phosphate Dehydrogenase Activity

    PubMed Central

    Maroni, Gustavo; Plaut, Walter

    1973-01-01

    The level of activity of the enzyme glucose-6-phosphate dehydrogenase was determinel in flies having seven different chromosomic constitutions. All those having an integral number of chromosomes [XAA, XXAA, XAAA, XXAAA, and XXXAAA (X=X chromosome, A=set of autosomes)] were found to have similar units of enzyme activity/mg live weight, while diploid females with a duplication and triploid females with a deficiency showed dosage effect. The amount of enzyme activity per cell, on the other hand, is also independent of the number of X's present but appears roughly proportional to the number of sets of autosomes.—It is proposed that dosage-compensated sex-linked genes are controlled by a positively acting regulatory factor(s) of autosomal origin. With this hypothesis it is possible to explain dosage compensation as a consequence of general regulatory mechanisms without invoking a special device which applies only to the X chromosomes. PMID:17248620

  1. Dosage Compensation in Sciarids Is Achieved by Hypertranscription of the Single X Chromosome in Males

    PubMed Central

    da-Cunha, P. R.; Granadino, B.; Perondini, ALP.; Sanchez, L.

    1994-01-01

    Dosage compensation refers to the process whereby females and males with different doses of sex chromosomes have similar amounts of products from sex chromosome-linked genes. We analyzed the process of dosage compensation in Sciara ocellaris, Diptera of the suborder Nematocera. By autoradiography and measurements of X-linked rRNA in females (XX) and males (XO), we found that the rate of transcription of the single X chromosome in males is similar to that of the two X chromosomes in females. This, together with the bloated appearance of the X chromosome in males, support the idea that in sciarids dosage compensation is accomplished by hypertranscription of the X chromosome in males. PMID:7851774

  2. 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. PMID:27045468

  3. Levothyroxine Dosage Requirement During Pregnancy in Well-Controlled Hypothyroid Women: A Longitudinal Study

    PubMed Central

    Kashi, Zahra; Bahar, Adele; Akha, Ozra; Hassanzade, Samane; Esmaeilisaraji, Leila; Hamzehgardeshi, Zeinab

    2016-01-01

    Background: Untreated maternal hypothyroidism can have adverse effects on both the mother and fetus, but it can potentially be prevented by adequate levothyroxine replacement. This study was conducted to determine what percentage of hypothyroid pregnant women who were taking levothyroxine needed to adjust their medication dosage, and when and how much it should be increased. Methods: In this longitudinal study, 81 well-controlled hypothyroid women (TSH≤ 2.5 mIU/L) were monitored throughout pregnancy. Thyroid function tests were performed before conception, after the first missed menstrual period, in the second and third trimesters of pregnancy and one month after delivery. Levothyroxine dosage was adjusted according to TSH levels measured. Results: Of the 81 pregnancies studied, the pregnancy outcomes were 74 full-term births, six abortions and one pre-term birth. The levothyroxine dosage needed to be increased in 84% (CI95%= 74-90) of the pregnancies (OR=5.2, CI95%= 2.9-9.4). Most levothyroxine dose adjustments were made in the first trimester of gestation. The levothyroxine requirement increased 50% (CI95%= 41-59) in the first trimester, 55% (CI95%= 45-64) in the second trimester and 62% (CI95%= 52-72) in the third trimester. Levothyroxine dosage was decreased for 6 cases (7.4%), and no adjustment was made for 7 women (8.6%). Conclusions: Increases in levothyroxine dosage administered in pregnancy appear to be indispensible in the majority of patients with well-controlled hypothyroidism, especially in the first trimester. However, this change was not universal and levothyroxine dosage decreased in a few cases and remained unchanged in others. PMID:26573046

  4. [Development of semisolid dosage form of clonazepam for oral cavity administration].

    PubMed

    Sakata, Osamu; Onishi, Hiraku; Machida, Yoshiharu

    2010-01-01

    A semisolid dosage form of clonazepam (CZP), administered to the oral cavity between the lower gum and bottom lip with small volume of saline, was developed to obtain the stable dosage which can replace the injection dosage form. Semisolid dosage forms were prepared using a mixture of CZP/(polyethylene glycol 1500 (PEG))/(oleic acid (OA)) at the ratios of 1/39/0, 1/37/2 and 2/36/2 (w/w), named CZP1-PEG, CZP1-PEG-OA and CZP2-PEG-OA, respectively, and were evaluated in vitro and in vivo. No crystal of CZP was observed in CZP1-PEG-OA for at least 8 days, while CZP crystal appeared before administration for CZP2-PEG-OA. When a small volume of saline was added to CZP1-PEG-OA just before the oral cavity administration, more than 80% (w/w) was found to exist in the soluble form. Each semisolid dosage form (40 mg) was administered to the oral cavity in rats, and CZP 1 mg suspension in 0.5% (w/v) sodium carboxymethylcellulose aqueous solution was administered into rat stomach as a control. CZP1-PEG-OA gave the plasma concentrations of more than 5 ng/ml and 12 ng/ml at 30 min and 1 h after administration, respectively, which might be near the plasma levels effective for the suppression of epileptic seizures in human, while the plasma concentration was less than 5 ng/ml at 30 min or did not reach 10 ng/ml at 1 h for the other formulations. It is proposed that the semisolid dosage form CZP1-PEG-OA should be a possibly useful preparation for the antiepileptic or sedative medication. PMID:20046075

  5. 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.

  6. Finding a Balance: How Diverse Dosage Compensation Strategies Modify Histone H4 to Regulate Transcription

    PubMed Central

    Wells, Michael B.; Csankovszki, Györgyi; Custer, Laura M.

    2012-01-01

    Dosage compensation balances gene expression levels between the sex chromosomes and autosomes and sex-chromosome-linked gene expression levels between the sexes. Different dosage compensation strategies evolved in different lineages, but all involve changes in chromatin. This paper discusses our current understanding of how modifications of the histone H4 tail, particularly changes in levels of H4 lysine 16 acetylation and H4 lysine 20 methylation, can be used in different contexts to either modulate gene expression levels twofold or to completely inhibit transcription. PMID:22567401

  7. Effect of low dosages of powdered activated carbon on membrane bioreactor performance.

    PubMed

    Remy, Maxime; Temmink, Hardy; Rulkens, Wim

    2012-01-01

    Previous research has demonstrated that powdered activated carbon (PAC), when applied at very low dosages and long SRTs, reduces membrane fouling in membrane bioreactors (MBRs). This effect was related to the formation of stronger sludge flocs, which are less sensitive to shear. In this contribution the long-term effect of PAC addition was studied by running two parallel MBRs on sewage. To one of these, PAC was dosed and a lower fouling tendency of the sludge was verified, with a 70% longer sustainable filtration time. Low PAC dosages showed additional advantages with regard to oxygen transfer and dewaterability, which may provide savings on operational costs. PMID:22339033

  8. 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

  9. Development and Validation of HPTLC Method for the Estimation of Almotriptan Malate in Tablet Dosage Form.

    PubMed

    Suneetha, A; Syamasundar, B

    2010-09-01

    A new, simple, precise and accurate high performance thin layer chromatographic method has been proposed for the determination of almotriptan malate in a tablet dosage form. The drug was separated on aluminum plates precoated with silica gel 60 GF(254) with butanol:acetic acid:water (3:1:1) was used as mobilephase. Quantitative analysis was performed by densitometric scanning at 300 nm. The method was validated for linearity, accuracy, precision and robustness. The calibration plot was linear over the range of 100-700 ng/band for almotriptan malate. The method was successfully applied to the analysis of drug in a pharmaceutical dosage form. PMID:21694997

  10. [Preparation and investigation of gemfibrozil + dimethyl-beta-cyclodextrin products and solid dosage forms].

    PubMed

    Hassan, Bin Hassan; Aigner, Zoltán; Kása, Péter; Hódi, Klára; Eros, István

    2005-01-01

    Gemfibrozil is a lipid-regulating active substance. Dimethyl-beta-cyclodextrin products were prepared from this sparingly soluble pharmacon by means of methods such as physical mixing, kneading, spray drying and ultrasonication. Solid dosage forms (hydroxypropylmethyl cellulose /HPMC/ capsules and tablets) were prepared from the selected products on the basis of their dissolution profile and the in vitro membrane diffusion results. This publication details the results of electronmicroscopic morphological studies, particle size analysis and wetting contact angle determinations, and also the preparation and examination of the resulting solid dosage forms. PMID:16318236

  11. 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

  12. EXPANDED STARCH AS A FLOATING DOSAGE MATRIX FOR THE CONTROLLED RELEASE OF MODEL DRUG COMPOUNDS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Starch-based materials were tested using model drug compounds to determine the feasibility of using starch as an oral floating dosage matrix. Oral controlled release systems require increased bio-availability, predictable release rates, and site-specific delivery. Starch and model drugs were compo...

  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. 75 FR 63085 - Certain Other Dosage Form New Animal Drugs; Progesterone Intravaginal Inserts

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-10-14

    ... HUMAN SERVICES Food and Drug Administration 21 CFR Part 529 Certain Other Dosage Form New Animal Drugs... Food and Drug Administration (FDA) is amending the animal drug regulations to reflect approval of a supplemental new animal drug application (NADA) filed by Pharmacia & Upjohn Co., a Division of Pfizer, Inc....

  15. 76 FR 49649 - Oral Dosage Form New Animal Drugs; Change of Sponsor; Chlortetracycline; Sulfamethazine

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-11

    ... Drug Administration 21 CFR Part 520 Oral Dosage Form New Animal Drugs; Change of Sponsor... and Drug Administration (FDA) is amending the animal drug regulations to reflect a change of sponsor for five new animal drug applications (NADAs) from Fort Dodge Animal Health, Division of...

  16. 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. PMID:25312492

  17. Spatial Colocalization of Human Ohnolog Pairs Acts to Maintain Dosage-Balance

    PubMed Central

    Xie, Ting; Yang, Qing-Yong; Wang, Xiao-Tao; McLysaght, Aoife; Zhang, Hong-Yu

    2016-01-01

    Ohnologs –paralogous gene pairs generated by whole genome duplication– are enriched for dosage sensitive genes, that is, genes that have a phenotype due to copy number changes. Dosage sensitive genes frequently occur in the same metabolic pathway and in physically interacting proteins. Accumulating evidence reveals that functionally related genes tend to co-localize in the three-dimensional (3D) arrangement of chromosomes. We query whether the spatial distribution of ohnologs has implications for their dosage balance. We analyzed the colocalization frequency of ohnologs based on chromatin interaction datasets of seven human cell lines and found that ohnolog pairs exhibit higher spatial proximity in 3D nuclear organization than other paralog pairs and than randomly chosen ohnologs in the genome. We also found that colocalized ohnologs are more resistant to copy number variations and more likely to be disease-associated genes, which indicates a stronger dosage balance in ohnologs with high spatial proximity. This phenomenon is further supported by the stronger similarity of gene co-expression and of gene ontology terms of colocalized ohnologs. In addition, for a large fraction of ohnologs, the spatial colocalization is conserved in mouse cells, suggestive of functional constraint on their 3D positioning in the nucleus. PMID:27297469

  18. Gene-dosage effects in Down syndrome and trisomic mouse models.

    PubMed

    Gardiner, Katheleen

    2004-01-01

    The abnormalities found in human Down syndrome (trisomy 21) have been thought to result from increased expression of genes on chromosome 21 because of their higher gene dosage. Now, several groups have shown this to be generally the case, but some inter-individual variability and other exceptions were found. PMID:15461808

  19. 10 CFR 35.2063 - Records of dosages of unsealed byproduct material for medical use.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 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,...

  20. 10 CFR 35.2063 - Records of dosages of unsealed byproduct material for medical use.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 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,...

  1. EFFECTS OF LOW DOSAGE OF STABLE STRONTIUM ON SERUM ENZYMES IN CHRONIC ALCOHOLICS

    EPA Science Inventory

    Systemic effects of low dosage of stable Sr2+ have not been investigated previously with respect to chronic ethanol abuse. e have previously demonstrated that Sr2+ may exert a protective effect against mitochondrial injury in rats. he baseline data for the present investigation w...

  2. 21 CFR 200.7 - Supplying pharmacists with indications and dosage information.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... supply such printed matter to the pharmacist for his professional information. Obviously, such printed... 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...

  3. 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,...

  4. Female mice lacking Xist RNA show partial dosage compensation and survive to term.

    PubMed

    Yang, Lin; Kirby, James E; Sunwoo, Hongjae; Lee, Jeannie T

    2016-08-01

    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

  5. 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)…

  6. 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

  7. Dosage compensation can buffer copy-number variation in wild yeast

    PubMed Central

    Hose, James; Yong, Chris Mun; Sardi, Maria; Wang, Zhishi; Newton, Michael A; Gasch, Audrey P

    2015-01-01

    Aneuploidy is linked to myriad diseases but also facilitates organismal evolution. It remains unclear how cells overcome the deleterious effects of aneuploidy until new phenotypes evolve. Although laboratory strains are extremely sensitive to aneuploidy, we show here that aneuploidy is common in wild yeast isolates, which show lower-than-expected expression at many amplified genes. We generated diploid strain panels in which cells carried two, three, or four copies of the affected chromosomes, to show that gene-dosage compensation functions at >30% of amplified genes. Genes subject to dosage compensation are under higher expression constraint in wild populations—but they show elevated rates of gene amplification, suggesting that copy-number variation is buffered at these genes. We find that aneuploidy provides a clear ecological advantage to oak strain YPS1009, by amplifying a causal gene that escapes dosage compensation. Our work presents a model in which dosage compensation buffers gene amplification through aneuploidy to provide a natural, but likely transient, route to rapid phenotypic evolution. DOI: http://dx.doi.org/10.7554/eLife.05462.001 PMID:25955966

  8. Modulation of Protein Levels in Chromosomal Dosage Series of Maize: The Biochemical Basis of Aneuploid Syndromes

    PubMed Central

    Birchler, James A.; Newton, Kathleen J.

    1981-01-01

    Genetically defined dosage series of chromosome arms 1L, 3L, 4S, 5L, 7L, 9S, 10L and combinations of 1L–3L, collectively spanning approximately one-third of the maize genome, were examined for alterations in the expression of total protein profiles in scutellar tissue. The major effects found were negative correlations of specific proteins with the dosage of particular regions in a manner similar to that previously described for enzyme activity levels (Birchler 1979). Chromosome arms 1L, 4S and 5L produced the most severe negative effects, with 3L and 7L exhibiting this phenomenon to a lesser degree. Positive correlations of certain proteins were observed with the dosage of the 1L, 3L, 5L and 7L regions. The structural locus of one of the major scutellar proteins (PRO) is present in the long arm of chromosome 1 (Schwartz 1979), but exhibits compensation in a dosage series involving whole-arm comparisons. Multiple factors in 1L affect the level of the protein. The compound TB-1La-3L4759-3 (1L 0.20–0.39) has a slight negative effect on PRO, while TB-1La-3Le (1L 0.20–0.58) and TB-1La-3L5267 (1L 0.20–0.72) have a more pronounced negative influence. The level of this protein is not altered by the dosage of 3L. These observations suggest that compensation is brought about by the cancellation of a positive structural gene dosage effect by the negative inverse effect. Other regions of the genome that contribute to the control of PRO levels are 4S and 5L. Total protein profiles were also compared in haploid, diploid and tetraploid maize as a comparison to the aneuploid series. Most proteins exhibit structural-gene-dosage effects through the ploidy series, but others show a positive effect greater than expected from varying the structural genes. Still others are negatively affected by ploidy changes. In general, the ploidy alterations are not as great as predicted from the cumulative action of the aneuploid effects. The bearing of these observations on the

  9. Linkage Analysis and QTL Mapping Using SNP Dosage Data in a Tetraploid Potato Mapping Population

    PubMed Central

    Hackett, Christine A.; McLean, Karen; Bryan, Glenn J.

    2013-01-01

    New sequencing and genotyping technologies have enabled researchers to generate high density SNP genotype data for mapping populations. In polyploid species, SNP data usually contain a new type of information, the allele dosage, which is not used by current methodologies for linkage analysis and QTL mapping. Here we extend existing methodology to use dosage data on SNPs in an autotetraploid mapping population. The SNP dosages are inferred from allele intensity ratios using normal mixture models. The steps of the linkage analysis (testing for distorted segregation, clustering SNPs, calculation of recombination fractions and LOD scores, ordering of SNPs and inference of parental phase) are extended to use the dosage information. For QTL analysis, the probability of each possible offspring genotype is inferred at a grid of locations along the chromosome from the ordered parental genotypes and phases and the offspring dosages. A normal mixture model is then used to relate trait values to the offspring genotypes and to identify the most likely locations for QTLs. These methods are applied to analyse a tetraploid potato mapping population of parents and 190 offspring, genotyped using an Infinium 8300 Potato SNP Array. Linkage maps for each of the 12 chromosomes are constructed. The allele intensity ratios are mapped as quantitative traits to check that their position and phase agrees with that of the corresponding SNP. This analysis confirms most SNP positions, and eliminates some problem SNPs to give high-density maps for each chromosome, with between 74 and 152 SNPs mapped and between 100 and 300 further SNPs allocated to approximate bins. Low numbers of double reduction products were detected. Overall 3839 of the 5378 polymorphic SNPs can be assigned putative genetic locations. This methodology can be applied to construct high-density linkage maps in any autotetraploid species, and could also be extended to higher autopolyploids. PMID:23704960

  10. [Brief discussion on "Sanli acupoint for du-fu diseases"].

    PubMed

    Zhou, Li; He, Quan; Xin, Yu; Zhang, Hongxing

    2015-07-01

    The connotations of "du-fu" and "Sanli" in "Sanli acupoint for du-fu diseases" are discussed in this paper, which can provide theoretical foundation for the clinical application of "Sanli acupoint for du-fu diseases". Based on ancient literature combined with related theories in the Huangdi Neijing (Yellow Emperor's Canon of Internal Classic), a deep discussion is performed through the relationship between Zusanli (ST 36) and stomach, indication and mechanism of Zusanli (ST 36) on du-fu diseases and comparison between Zusanli (ST 36) and Shousanli (LI 10). It is believed that "du" should be pronounced as "dŭ", meaning stomach, and it indicates that Zusanli (ST 36) is closely related to stomach and spleen when it is used for du-fu diseases; "fu" means abdomen area, including liver-gallbladder, spleen, stomach-intestine, kidney, uterus, triple energizer; "sanli' means exclusively the acupoint of Zusanli (ST 36). PMID:26521594