X chromosome dosage compensation via enhanced transcriptional elongation in Drosophila.

Science.gov (United States)

Larschan, Erica; Bishop, Eric P; Kharchenko, Peter V; Core, Leighton J; Lis, John T; Park, Peter J; Kuroda, Mitzi I

2011-03-03

The evolution of sex chromosomes has resulted in numerous species in which females inherit two X chromosomes but males have a single X, thus requiring dosage compensation. MSL (Male-specific lethal) complex increases transcription on the single X chromosome of Drosophila males to equalize expression of X-linked genes between the sexes. The biochemical mechanisms used for dosage compensation must function over a wide dynamic range of transcription levels and differential expression patterns. It has been proposed that the MSL complex regulates transcriptional elongation to control dosage compensation, a model subsequently supported by mapping of the MSL complex and MSL-dependent histone 4 lysine 16 acetylation to the bodies of X-linked genes in males, with a bias towards 3' ends. However, experimental analysis of MSL function at the mechanistic level has been challenging owing to the small magnitude of the chromosome-wide effect and the lack of an in vitro system for biochemical analysis. Here we use global run-on sequencing (GRO-seq) to examine the specific effect of the MSL complex on RNA Polymerase II (RNAP II) on a genome-wide level. Results indicate that the MSL complex enhances transcription by facilitating the progression of RNAP II across the bodies of active X-linked genes. Improving transcriptional output downstream of typical gene-specific controls may explain how dosage compensation can be imposed on the diverse set of genes along an entire chromosome.

A brief history of dosage compensation

Indian Academy of Sciences (India)

depression of X-linked gene activity in the female, as well as by hyperexpression of the ... to the Harvey lecture, Muller had presented important ideas relative to dosage ... at Columbia. I do recall a talk by the popular physical anthro- pologist ...

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

OpenAIRE

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...

The gene dosage effect of the rad52 mutation on X-ray survival curves of tetraploid yeast strains

International Nuclear Information System (INIS)

Ho, K.S.Y.

1975-01-01

The mutation rad52 in the yeast Saccharomyces cerevisiae confers sensitivity to X-rays. The gene dosage effect of this mutation on X-ray survival curves of tetraploid yeast strains is shown. With increasing number of rad52 alleles, both a decrease in the survival for a given dose and a decrease in the survival curve shoulder width are observed. The generation of such a family of survival curves using three different mathematical models is discussed

Incomplete sex chromosome dosage compensation in the Indian meal moth, Plodia interpunctella, based on de novo transcriptome assembly.

Science.gov (United States)

Harrison, Peter W; Mank, Judith E; Wedell, Nina

2012-01-01

Males and females experience differences in gene dose for loci in the nonrecombining region of heteromorphic sex chromosomes. If not compensated, this leads to expression imbalances, with the homogametic sex on average exhibiting greater expression due to the doubled gene dose. Many organisms with heteromorphic sex chromosomes display global dosage compensation mechanisms, which equalize gene expression levels between the sexes. However, birds and Schistosoma have been previously shown to lack chromosome-wide dosage compensation mechanisms, and the status in other female heterogametic taxa including Lepidoptera remains unresolved. To further our understanding of dosage compensation in female heterogametic taxa and to resolve its status in the lepidopterans, we assessed the Indian meal moth, Plodia interpunctella. As P. interpunctella lacks a complete reference genome, we conducted de novo transcriptome assembly combined with orthologous genomic location prediction from the related silkworm genome, Bombyx mori, to compare Z-linked and autosomal gene expression levels for each sex. We demonstrate that P. interpunctella lacks complete Z chromosome dosage compensation, female Z-linked genes having just over half the expression level of males and autosomal genes. This finding suggests that the Lepidoptera and possibly all female heterogametic taxa lack global dosage compensation, although more species will need to be sampled to confirm this assertion.

Feeding-Related Traits Are Affected by Dosage of the foraging Gene in Drosophila melanogaster.

Science.gov (United States)

Allen, Aaron M; Anreiter, Ina; Neville, Megan C; Sokolowski, Marla B

2017-02-01

Nutrient acquisition and energy storage are critical parts of achieving metabolic homeostasis. The foraging gene in Drosophila melanogaster has previously been implicated in multiple feeding-related and metabolic traits. Before foraging's functions can be further dissected, we need a precise genetic null mutant to definitively map its amorphic phenotypes. We used homologous recombination to precisely delete foraging, generating the for 0 null allele, and used recombineering to reintegrate a full copy of the gene, generating the {for BAC } rescue allele. We show that a total loss of foraging expression in larvae results in reduced larval path length and food intake behavior, while conversely showing an increase in triglyceride levels. Furthermore, varying foraging gene dosage demonstrates a linear dose-response on these phenotypes in relation to foraging gene expression levels. These experiments have unequivocally proven a causal, dose-dependent relationship between the foraging gene and its pleiotropic influence on these feeding-related traits. Our analysis of foraging's transcription start sites, termination sites, and splicing patterns using rapid amplification of cDNA ends (RACE) and full-length cDNA sequencing, revealed four independent promoters, pr1-4, that produce 21 transcripts with nine distinct open reading frames (ORFs). The use of alternative promoters and alternative splicing at the foraging locus creates diversity and flexibility in the regulation of gene expression, and ultimately function. Future studies will exploit these genetic tools to precisely dissect the isoform- and tissue-specific requirements of foraging's functions and shed light on the genetic control of feeding-related traits involved in energy homeostasis. Copyright © 2017 by the Genetics Society of America.

Expansion of GA Dinucleotide Repeats Increases the Density of CLAMP Binding Sites on the X-Chromosome to Promote Drosophila Dosage Compensation.

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Guray Kuzu

2016-07-01

Full Text Available Dosage compensation is an essential process that equalizes transcript levels of X-linked genes between sexes by forming a domain of coordinated gene expression. Throughout the evolution of Diptera, many different X-chromosomes acquired the ability to be dosage compensated. Once each newly evolved X-chromosome is targeted for dosage compensation in XY males, its active genes are upregulated two-fold to equalize gene expression with XX females. In Drosophila melanogaster, the CLAMP zinc finger protein links the dosage compensation complex to the X-chromosome. However, the mechanism for X-chromosome identification has remained unknown. Here, we combine biochemical, genomic and evolutionary approaches to reveal that expansion of GA-dinucleotide repeats likely accumulated on the X-chromosome over evolutionary time to increase the density of CLAMP binding sites, thereby driving the evolution of dosage compensation. Overall, we present new insight into how subtle changes in genomic architecture, such as expansions of a simple sequence repeat, promote the evolution of coordinated gene expression.

Identification of chromatin-associated regulators of MSL complex targeting in Drosophila dosage compensation.

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Erica Larschan

Full Text Available Sex chromosome dosage compensation in Drosophila provides a model for understanding how chromatin organization can modulate coordinate gene regulation. Male Drosophila increase the transcript levels of genes on the single male X approximately two-fold to equal the gene expression in females, which have two X-chromosomes. Dosage compensation is mediated by the Male-Specific Lethal (MSL histone acetyltransferase complex. Five core components of the MSL complex were identified by genetic screens for genes that are specifically required for male viability and are dispensable for females. However, because dosage compensation must interface with the general transcriptional machinery, it is likely that identifying additional regulators that are not strictly male-specific will be key to understanding the process at a mechanistic level. Such regulators would not have been recovered from previous male-specific lethal screening strategies. Therefore, we have performed a cell culture-based, genome-wide RNAi screen to search for factors required for MSL targeting or function. Here we focus on the discovery of proteins that function to promote MSL complex recruitment to "chromatin entry sites," which are proposed to be the initial sites of MSL targeting. We find that components of the NSL (Non-specific lethal complex, and a previously unstudied zinc-finger protein, facilitate MSL targeting and display a striking enrichment at MSL entry sites. Identification of these factors provides new insight into how MSL complex establishes the specialized hyperactive chromatin required for dosage compensation in Drosophila.

General lack of global dosage compensation in ZZ/ZW systems? Broadening the perspective with RNA-seq

Directory of Open Access Journals (Sweden)

Wolf Jochen BW

2011-02-01

Full Text Available Abstract Background Species with heteromorphic sex chromosomes face the challenge of large-scale imbalance in gene dose. Microarray-based studies in several independent male heterogametic XX/XY systems suggest that dosage compensation mechanisms are in place to mitigate the detrimental effects of gene dose differences. However, recent genomic research on female heterogametic ZZ/ZW systems has generated surprising results. In two bird species and one lepidopteran no evidence for a global dosage compensating mechanism has been found. The recent advent of massively parallel RNA sequencing now opens up the possibility to gauge the generality of this observation with a broader phylogenetic sampling. It further allows assessing the validity of microarray-based inference on dosage compensation with a novel technology. Results We here expemplify this approach using massively parallel sequencing on barcoded individuals of a bird species, the European crow (Corvus corone, where previously no genetic resources were available. Testing for Z-linkage with quantitative PCR (qPCR, we first establish that orthology with distantly related species (chicken, zebra finch can be used as a good predictor for chromosomal affiliation of a gene. We then use a digital measure of gene expression (RNA-seq on brain transcriptome and confirm a global lack of dosage compensation on the Z chromosome. RNA-seq estimates of male-to-female (m:f expression difference on the Z compare well to previous microarray-based estimates in birds and lepidopterans. The data further lends support that an up-regulation of female Z-linked genes conveys partial compensation and suggest a relationship between sex-bias and absolute expression level of a gene. Correlation of sex-biased gene expression on the Z chromosome across all three bird species further suggests that the degree of compensation has been partly conserved across 100 million years of avian evolution. Conclusions This work

Analysis of the dosage compensation of a specific transcript in Drosophila melanogaster

International Nuclear Information System (INIS)

Breen, T.R.

1985-01-01

The basic tenet of dosage compensation is that males, which normally have one X-chromosome that contains half the amount of DNA as the two X-chromosomes in females, produce a relatively equivalent amount of X-encoded gene products compared to females. Quantitative analyses were performed to ascertain the amount of transcripts synthesized from the X-linked salivary gland secretion protein gene, Sgs-4, in larval third instar males and females which had a variety of genetic backgrounds. Two types of analyses were performed. In one, RNA from male and female late third instar salivary glands was isolated and quantitatively blotted to replica nitrocellulose filters. The replicas were hybridized with 32 P-labeled probes specific for either Sgs-4 or Sgs-3 RNA. The radioactive hybrids were quantitated by scintillation counting. In the other, male and female third instar salivary glands were incubated for 12.5 minutes with 3 H-uridine. The labelled, nascent RNAs were hybridized to dot blots of Sgs-4 and Sgs-3 DNA, and were scintillation counted. 3 H-uridine incorporation analysis showed that male Sgs-4 genes were transcribed at twice the rate of the female genes. These findings indicated that steady-state Sgs-4 RNA levels directly reflect the rate of their transcription. These results are important in that they demonstrate that dosage compensation operates at the level of the rate of transcription of a specific gene. They also dissolve ambiguities associated with results obtained in past dosage compensation experiments

Histone dosage regulates DNA damage sensitivity in a checkpoint-independent manner by the homologous recombination pathway

Science.gov (United States)

Liang, Dun; Burkhart, Sarah Lyn; Singh, Rakesh Kumar; Kabbaj, Marie-Helene Miquel; Gunjan, Akash

2012-01-01

In eukaryotes, multiple genes encode histone proteins that package genomic deoxyribonucleic acid (DNA) and regulate its accessibility. Because of their positive charge, ‘free’ (non-chromatin associated) histones can bind non-specifically to the negatively charged DNA and affect its metabolism, including DNA repair. We have investigated the effect of altering histone dosage on DNA repair in budding yeast. An increase in histone gene dosage resulted in enhanced DNA damage sensitivity, whereas deletion of a H3–H4 gene pair resulted in reduced levels of free H3 and H4 concomitant with resistance to DNA damaging agents, even in mutants defective in the DNA damage checkpoint. Studies involving the repair of a HO endonuclease-mediated DNA double-strand break (DSB) at the MAT locus show enhanced repair efficiency by the homologous recombination (HR) pathway on a reduction in histone dosage. Cells with reduced histone dosage experience greater histone loss around a DSB, whereas the recruitment of HR factors is concomitantly enhanced. Further, free histones compete with the HR machinery for binding to DNA and associate with certain HR factors, potentially interfering with HR-mediated repair. Our findings may have important implications for DNA repair, genomic stability, carcinogenesis and aging in human cells that have dozens of histone genes. PMID:22850743

Genetic basis for dosage sensitivity in Arabidopsis thaliana.

Directory of Open Access Journals (Sweden)

Isabelle M Henry

2007-04-01

Full Text Available Aneuploidy, the relative excess or deficiency of specific chromosome types, results in gene dosage imbalance. Plants can produce viable and fertile aneuploid individuals, while most animal aneuploids are inviable or developmentally abnormal. The swarms of aneuploid progeny produced by Arabidopsis triploids constitute an excellent model to investigate the mechanisms governing dosage sensitivity and aneuploid syndromes. Indeed, genotype alters the frequency of aneuploid types within these swarms. Recombinant inbred lines that were derived from a triploid hybrid segregated into diploid and tetraploid individuals. In these recombinant inbred lines, a single locus, which we call SENSITIVE TO DOSAGE IMBALANCE (SDI, exhibited segregation distortion in the tetraploid subpopulation only. Recent progress in quantitative genotyping now allows molecular karyotyping and genetic analysis of aneuploid populations. In this study, we investigated the causes of the ploidy-specific distortion at SDI. Allele frequency was distorted in the aneuploid swarms produced by the triploid hybrid. We developed a simple quantitative measure for aneuploidy lethality and using this measure demonstrated that distortion was greatest in the aneuploids facing the strongest viability selection. When triploids were crossed to euploids, the progeny, which lack severe aneuploids, exhibited no distortion at SDI. Genetic characterization of SDI in the aneuploid swarm identified a mechanism governing aneuploid survival, perhaps by buffering the effects of dosage imbalance. As such, SDI could increase the likelihood of retaining genomic rearrangements such as segmental duplications. Additionally, in species where triploids are fertile, aneuploid survival would facilitate gene flow between diploid and tetraploid populations via a triploid bridge and prevent polyploid speciation. Our results demonstrate that positional cloning of loci affecting traits in populations containing ploidy and

Tissue- and stage-dependent dosage compensation on the Neo-X chromosome in drosophila pseudoobscura

KAUST Repository

Nozawa, Masafumi; Fukuda, Nana; Ikeo, Kazuho; Gojobori, Takashi

2013-01-01

Sex chromosome dosage compensation (DC) is widely accepted in various organisms. This concept is mostly supported by comparisons of gene expression between chromosomes and between sexes. However, genes on the X chromosome and autosomes are mostly

Mechanisms and evolutionary patterns of mammalian and avian dosage compensation.

Directory of Open Access Journals (Sweden)

Philippe Julien

Full Text Available As a result of sex chromosome differentiation from ancestral autosomes, male mammalian cells only contain one X chromosome. It has long been hypothesized that X-linked gene expression levels have become doubled in males to restore the original transcriptional output, and that the resulting X overexpression in females then drove the evolution of X inactivation (XCI. However, this model has never been directly tested and patterns and mechanisms of dosage compensation across different mammals and birds generally remain little understood. Here we trace the evolution of dosage compensation using extensive transcriptome data from males and females representing all major mammalian lineages and birds. Our analyses suggest that the X has become globally upregulated in marsupials, whereas we do not detect a global upregulation of this chromosome in placental mammals. However, we find that a subset of autosomal genes interacting with X-linked genes have become downregulated in placentals upon the emergence of sex chromosomes. Thus, different driving forces may underlie the evolution of XCI and the highly efficient equilibration of X expression levels between the sexes observed for both of these lineages. In the egg-laying monotremes and birds, which have partially homologous sex chromosome systems, partial upregulation of the X (Z in birds evolved but is largely restricted to the heterogametic sex, which provides an explanation for the partially sex-biased X (Z expression and lack of global inactivation mechanisms in these lineages. Our findings suggest that dosage reductions imposed by sex chromosome differentiation events in amniotes were resolved in strikingly different ways.

Condensin-driven remodelling of X chromosome topology during dosage compensation

Science.gov (United States)

Crane, Emily; Bian, Qian; McCord, Rachel Patton; Lajoie, Bryan R.; Wheeler, Bayly S.; Ralston, Edward J.; Uzawa, Satoru; Dekker, Job; Meyer, Barbara J.

2015-07-01

The three-dimensional organization of a genome plays a critical role in regulating gene expression, yet little is known about the machinery and mechanisms that determine higher-order chromosome structure. Here we perform genome-wide chromosome conformation capture analysis, fluorescent in situ hybridization (FISH), and RNA-seq to obtain comprehensive three-dimensional (3D) maps of the Caenorhabditis elegans genome and to dissect X chromosome dosage compensation, which balances gene expression between XX hermaphrodites and XO males. The dosage compensation complex (DCC), a condensin complex, binds to both hermaphrodite X chromosomes via sequence-specific recruitment elements on X (rex sites) to reduce chromosome-wide gene expression by half. Most DCC condensin subunits also act in other condensin complexes to control the compaction and resolution of all mitotic and meiotic chromosomes. By comparing chromosome structure in wild-type and DCC-defective embryos, we show that the DCC remodels hermaphrodite X chromosomes into a sex-specific spatial conformation distinct from autosomes. Dosage-compensated X chromosomes consist of self-interacting domains (~1 Mb) resembling mammalian topologically associating domains (TADs). TADs on X chromosomes have stronger boundaries and more regular spacing than on autosomes. Many TAD boundaries on X chromosomes coincide with the highest-affinity rex sites and become diminished or lost in DCC-defective mutants, thereby converting the topology of X to a conformation resembling autosomes. rex sites engage in DCC-dependent long-range interactions, with the most frequent interactions occurring between rex sites at DCC-dependent TAD boundaries. These results imply that the DCC reshapes the topology of X chromosomes by forming new TAD boundaries and reinforcing weak boundaries through interactions between its highest-affinity binding sites. As this model predicts, deletion of an endogenous rex site at a DCC-dependent TAD boundary using

Dosage Compensation of an Aneuploid Genome in Mouse Spermatogenic Cells

Czech Academy of Sciences Publication Activity Database

Jansa, Petr; Homolka, David; Blatný, Radek; Mistrik, M.; Bartek, Jiří; Forejt, Jiří

2014-01-01

Roč. 90, č. 6 (2014), 124/1-124/9 ISSN 0006-3363 R&D Projects: GA ČR GA13-08078S Institutional support: RVO:68378050 Keywords : gene dosage * male sterility * segmental trisomy * meiotic silencing of unsynapsed chromatin * DOWN-SYNDROME * MAMMALIAN MEIOSIS Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.318, year: 2014

Dosage Compensation of an Aneuploid Genome in Mouse Spermatogenic Cells

Czech Academy of Sciences Publication Activity Database

Jansa, Petr; Homolka, David; Blatný, Radek; Mistrik, M.; Bartek, Jiří; Forejt, Jiří

2014-01-01

Roč. 90, č. 6 (2014), 124/1-124/9 ISSN 0006-3363 R&D Projects: GA ČR GA13-08078S Institutional support: RVO:68378050 Keywords : gene dosage * male sterility * segmental trisomy * meiotic silencing of unsynapsed chromatin * DOWN - SYNDROME * MAMMALIAN MEIOSIS Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.318, year: 2014

Fear-Specific Amygdala Function in Children and Adolescents on the Fragile X Spectrum: A Dosage Response of the FMR1 Gene

Science.gov (United States)

Kim, So-Yeon; Burris, Jessica; Bassal, Frederick; Koldewyn, Kami; Chattarji, Sumantra; Tassone, Flora; Hessl, David; Rivera, Susan M.

2014-01-01

Mutations of the fragile X mental retardation 1 (FMR1) gene are the genetic cause of fragile X syndrome (FXS). The presence of significant socioemotional problems has been well documented in FXS although the brain basis of those deficits remains unspecified. Here, we investigated amygdala dysfunction and its relation to socioemotional deficits and FMR1 gene expression in children and adolescents on the FX spectrum (i.e., individuals whose trinucleotide CGG repeat expansion from 55 to over 200 places them somewhere within the fragile X diagnostic range from premutation to full mutation). Participants performed an fMRI task in which they viewed fearful, happy, and scrambled faces. Neuroimaging results demonstrated that FX participants revealed significantly attenuated amygdala activation in Fearful > Scrambled and Fearful > Happy contrasts compared with their neurotypical counterparts, while showing no differences in amygdala volume. Furthermore, we found significant relationships between FMR1 gene expression, anxiety/social dysfunction scores, and reduced amygdala activation in the FX group. In conclusion, we report novel evidence regarding a dosage response of the FMR1 gene on fear-specific functions of the amygdala, which is associated with socioemotional deficits in FXS. PMID:23146966

Reciprocal Relationship between Head Size, an Autism Endophenotype, and Gene Dosage at 19p13.12 Points to AKAP8 and AKAP8L.

Directory of Open Access Journals (Sweden)

Rebecca A Nebel

Full Text Available Microcephaly and macrocephaly are overrepresented in individuals with autism and are thought to be disease-related risk factors or endophenotypes. Analysis of DNA microarray results from a family with a low functioning autistic child determined that the proband and two additional unaffected family members who carry a rare inherited 760 kb duplication of unknown clinical significance at 19p13.12 are macrocephalic. Consideration alongside overlapping deletion and duplication events in the literature provides support for a strong relationship between gene dosage at this locus and head size, with losses and gains associated with microcephaly (p=1.11x10(-11 and macrocephaly (p=2.47x10(-11, respectively. Data support A kinase anchor protein 8 and 8-like (AKAP8 and AKAP8L as candidate genes involved in regulation of head growth, an interesting finding given previous work implicating the AKAP gene family in autism. Towards determination of which of AKAP8 and AKAP8L may be involved in the modulation of head size and risk for disease, we analyzed exome sequencing data for 693 autism families (2591 individuals where head circumference data were available. No predicted loss of function variants were observed, precluding insights into relationship to head size, but highlighting strong evolutionary conservation. Taken together, findings support the idea that gene dosage at 19p13.12, and AKAP8 and/or AKAP8L in particular, play an important role in modulation of head size and may contribute to autism risk. Exome sequencing of the family also identified a rare inherited variant predicted to disrupt splicing of TPTE / PTEN2, a PTEN homologue, which may likewise contribute to both macrocephaly and autism risk.

Dosage compensation in Drosophila melanogaster, a model for control in other insect species

International Nuclear Information System (INIS)

Hilfiker, A.; Hilfiker-Kleiner, D.; Lucchesi, J.C.

1998-01-01

In the animal kingdom, many species with euchromatic heteromorphic sex chromosomes have developed mechanisms for the equalization of gene products in the homo- and the heterogametic sex. This mechanism, called dosage compensation, is achieved in Drosophila by the doubling of the transcriptional activity of X-linked genes in the male, in comparison to the female. Any failure in achieving dosage compensation causes lethality: hapto-X male individuals that fail to hyperactivate their single X-chromosome as well as diplo-X female individuals that hyperactivate their X-chromosomes die. Five genes that are involved in the regulation of this process have been identified. in males, a group of four genes, the so called male-specific lethals (mle, msl-1, msl-2, msl-3), must be active in order for hypertranscription to occur, whereas in females the Sxl gene, the master key gene of sex determination, has to be active to prevent the msl genes from becoming active. However, XX individuals with mutations in Sxl cannot be rescued by mutations in the msl genes indicating that at least one member of this group is yet to be uncovered. Furthermore, the msl gene that is regulated in a sex-specific manner has not yet been identified. Given that msl-1 is transcribed in both sexes but its protein product is nearly absent in females, we have investigated whether this gene is the target of sex-specific regulation. We have also carried out extensive genetic screens for the purpose of identifying additional members of the msl group. These investigations are necessary prerequisites to the development of genetic sexing techniques based on the constitutive expression of msl genes in females causing female-specific lethality. (author)

“Jump Start and Gain” Model for Dosage Compensation in Drosophila Based on Direct Sequencing of Nascent Transcripts

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Francesco Ferrari

2013-11-01

Full Text Available Dosage compensation in Drosophila is mediated by the MSL complex, which increases male X-linked gene expression approximately 2-fold. The MSL complex preferentially binds the bodies of active genes on the male X, depositing H4K16ac with a 3′ bias. Two models have been proposed for the influence of the MSL complex on transcription: one based on promoter recruitment of RNA polymerase II (Pol II, and a second featuring enhanced transcriptional elongation. Here, we utilize nascent RNA sequencing to document dosage compensation during transcriptional elongation. We also compare X and autosomes from published data on paused and elongating polymerase in order to assess the role of Pol II recruitment. Our results support a model for differentially regulated elongation, starting with release from 5′ pausing and increasing through X-linked gene bodies. Our results highlight facilitated transcriptional elongation as a key mechanism for the coordinated regulation of a diverse set of genes.

Incorrect dosage of IQSEC2, a known intellectual disability and epilepsy gene, disrupts dendritic spine morphogenesis

Science.gov (United States)

Hinze, S J; Jackson, M R; Lie, S; Jolly, L; Field, M; Barry, S C; Harvey, R J; Shoubridge, C

2017-01-01

There is considerable genetic and phenotypic heterogeneity associated with intellectual disability (ID), specific learning disabilities, attention-deficit hyperactivity disorder, autism and epilepsy. The intelligence quotient (IQ) motif and SEC7 domain containing protein 2 gene (IQSEC2) is located on the X-chromosome and harbors mutations that contribute to non-syndromic ID with and without early-onset seizure phenotypes in both sexes. Although IQ and Sec7 domain mutations lead to partial loss of IQSEC2 enzymatic activity, the in vivo pathogenesis resulting from these mutations is not known. Here we reveal that IQSEC2 has a key role in dendritic spine morphology. Partial loss-of-function mutations were modeled using a lentiviral short hairpin RNA (shRNA) approach, which achieved a 57% knockdown of Iqsec2 expression in primary hippocampal cell cultures from mice. Investigating gross morphological parameters after 8 days of in vitro culture (8DIV) identified a 32% reduction in primary axon length, in contrast to a 27% and 31% increase in the number and complexity of dendrites protruding from the cell body, respectively. This increase in dendritic complexity and spread was carried through dendritic spine development, with a 34% increase in the number of protrusions per dendritic segment compared with controls at 15DIV. Although the number of dendritic spines had normalized by 21DIV, a reduction was noted in the number of immature spines. In contrast, when modeling increased dosage, overexpression of wild-type IQSEC2 led to neurons with shorter axons that were more compact and displayed simpler dendritic branching. Disturbances to dendritic morphology due to knockdown of Iqsec2 were recapitulated in neurons from Iqsec2 knockout mice generated in our laboratory using CRISPR/Cas9 technology. These observations provide evidence of dosage sensitivity for IQSEC2, which normally escapes X-inactivation in females, and links these disturbances in expression to alterations in

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

Science.gov (United States)

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

2012-10-05

The design and selection of new pharmaceutical dosage forms involves the careful consideration and balancing of a quality target product profile against technical challenges and development feasibility. Paediatric dosage forms present particular complexity due to the diverse patient population, patient compliance challenges and safety considerations of this vulnerable population. This paper presents a structured framework for assessing the comparative benefits and risks of different pharmaceutical design options against pre-determined criteria relating to (1) efficacy, (2) safety and (3) patient access. This benefit/risk framework has then been applied to three hypothetical, but realistic, scenarios for paediatric dosage forms in order to explore its utility in guiding dosage form design and formulation selection. The approach allows a rigorous, systematic and qualitative assessment of the merits and disadvantages of each dosage form option and helps identify mitigating strategies to modify risk. The application of a weighting and scoring system to the criteria depending on the specific case could further refine the analysis and aid decision-making. In this paper, one case study is scored for illustrative purposes. However, it is acknowledged that in real development scenarios, the generation of actual data considering the very specific situation for the patient/product/developer would come into play to drive decisions on the most appropriate dosage form strategy. Copyright © 2012 Elsevier B.V. All rights reserved.

Gene expression analysis identifies global gene dosage sensitivity in cancer

DEFF Research Database (Denmark)

Fehrmann, Rudolf S. N.; Karjalainen, Juha M.; Krajewska, Malgorzata

2015-01-01

Many cancer-associated somatic copy number alterations (SCNAs) are known. Currently, one of the challenges is to identify the molecular downstream effects of these variants. Although several SCNAs are known to change gene expression levels, it is not clear whether each individual SCNA affects gen...

Dosage effect of a Phex mutation in a murine model of X-linked hypophosphatemia

Science.gov (United States)

Ichikawa, Shoji; Gray, Amie K.; Bikorimana, Emmanuel; Econs, Michael J.

2013-01-01

X-linked hypophosphatemia (XLH) is caused by mutations in the PHEX gene, which increase circulating levels of the phosphaturic hormone, fibroblast growth factor 23 (FGF23). Since XLH is a dominant disease, one mutant allele is sufficient for manifestation of the disease. However, dosage effect of a PHEX mutation in XLH is not completely understood. To examine the effect of Phex genotypes, we compared serum biochemistries and skeletal measures between all five possible genotypes of a new murine model of XLH (PhexK496X or PhexJrt). Compared to sex-matched littermate controls, all Phex mutant mice had hypophosphatemia, mild hypocalcemia, and increased parathyroid hormone and alkaline phosphatase levels. Furthermore, mutant mice had markedly elevated serum Fgf23 levels due to increased Fgf23 expression and reduced cleavage of Fgf23. Although females with a homozygous Phex mutation were slightly more hypocalcemic and hypophosphatemic than heterozygous females, the two groups had comparable intact Fgf23 levels. Similarly, there was no difference in intact Fgf23 or phosphorus concentrations between hemizygous males and heterozygous females. Compared to heterozygous females, homozygous counterparts were significantly smaller and had shorter femurs with reduced bone mineral density, suggesting the existence of dosage effect in the skeletal phenotype of XLH. However, overall phenotypic trends in regards to mineral ion homeostasis were mostly unaffected by the presence of one or two mutant Phex allele(s). The lack of gene dosage effect on circulating Fgf23 (and thus, phosphorus) levels suggests that a Phex mutation may create the lower set point for extracellular phosphate concentrations. PMID:23700148

The association between GGCX, miR-133 genetic polymorphisms and warfarin stable dosage in Han Chinese patients with mechanical heart valve replacement.

Science.gov (United States)

Tang, X-Y; Zhang, J; Peng, J; Tan, S-L; Zhang, W; Song, G-B; Liu, L-M; Li, C-L; Ren, H; Zeng, L; Liu, Z-Q; Chen, X-P; Zhou, X-M; Zhou, H-H; Hu, J-X; Li, Z

2017-08-01

Warfarin is a widely used anticoagulant with a narrow therapeutic index. Polymorphisms in the VKORC1, CYP2C9 and CYP4F2 genes have been verified to correlate with warfarin stable dosage (WSD). Whether any other genes or variants affect the dosage is unknown. The aim of our study was to investigate the relationship between GGCX, miR-133 variants and the WSD in Han Chinese patients with mechanical heart valve replacement (MHVR). A total of 231 patients were enrolled in the study. Blood samples were collected for genotyping. The average WSD among subjects with different GGCX or miR-133 genotypes was compared. Regression analyses were performed to test for any association of genetic polymorphisms with WSD. The warfarin dosage in patients with the GGCX rs699664 TT and rs12714145 TT genotypes was 3.77±0.93 (95% CI: 3.35-4.19) mg/d and 3.70±1.00 (95% CI: 3.32-4.09) mg/d, respectively. The GGCX rs699664 and rs12714145 genotypes were significantly associated with WSD (Pwarfarin stable dosage between subjects with MIR133B rs142410335 wild-type and variant genotypes (P>.05). The genotypes of GGCX rs699644 and rs12714145 were significantly associated with WSD (Pwarfarin stable dosage in Han Chinese patients with MHVR neither in univariate regression nor in multivariate regression analyses. © 2017 John Wiley & Sons Ltd.

Effects of Gene Dose, Chromatin, and Network Topology on Expression in Drosophila melanogaster.

Directory of Open Access Journals (Sweden)

Hangnoh Lee

2016-09-01

Full Text Available Deletions, commonly referred to as deficiencies by Drosophila geneticists, are valuable tools for mapping genes and for genetic pathway discovery via dose-dependent suppressor and enhancer screens. More recently, it has become clear that deviations from normal gene dosage are associated with multiple disorders in a range of species including humans. While we are beginning to understand some of the transcriptional effects brought about by gene dosage changes and the chromosome rearrangement breakpoints associated with them, much of this work relies on isolated examples. We have systematically examined deficiencies of the left arm of chromosome 2 and characterize gene-by-gene dosage responses that vary from collapsed expression through modest partial dosage compensation to full or even over compensation. We found negligible long-range effects of creating novel chromosome domains at deletion breakpoints, suggesting that cases of gene regulation due to altered nuclear architecture are rare. These rare cases include trans de-repression when deficiencies delete chromatin characterized as repressive in other studies. Generally, effects of breakpoints on expression are promoter proximal (~100bp or in the gene body. Effects of deficiencies genome-wide are in genes with regulatory relationships to genes within the deleted segments, highlighting the subtle expression network defects in these sensitized genetic backgrounds.

Effects of Gene Dose, Chromatin, and Network Topology on Expression in Drosophila melanogaster.

Science.gov (United States)

Lee, Hangnoh; Cho, Dong-Yeon; Whitworth, Cale; Eisman, Robert; Phelps, Melissa; Roote, John; Kaufman, Thomas; Cook, Kevin; Russell, Steven; Przytycka, Teresa; Oliver, Brian

2016-09-01

Deletions, commonly referred to as deficiencies by Drosophila geneticists, are valuable tools for mapping genes and for genetic pathway discovery via dose-dependent suppressor and enhancer screens. More recently, it has become clear that deviations from normal gene dosage are associated with multiple disorders in a range of species including humans. While we are beginning to understand some of the transcriptional effects brought about by gene dosage changes and the chromosome rearrangement breakpoints associated with them, much of this work relies on isolated examples. We have systematically examined deficiencies of the left arm of chromosome 2 and characterize gene-by-gene dosage responses that vary from collapsed expression through modest partial dosage compensation to full or even over compensation. We found negligible long-range effects of creating novel chromosome domains at deletion breakpoints, suggesting that cases of gene regulation due to altered nuclear architecture are rare. These rare cases include trans de-repression when deficiencies delete chromatin characterized as repressive in other studies. Generally, effects of breakpoints on expression are promoter proximal (~100bp) or in the gene body. Effects of deficiencies genome-wide are in genes with regulatory relationships to genes within the deleted segments, highlighting the subtle expression network defects in these sensitized genetic backgrounds.

[Pharmaceutical advice concerning different pharmaceutical dosage forms].

Science.gov (United States)

Szakonyi, Gergely; Zelkó, Romána

2010-01-01

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

Low starting dosage of infliximab with possible escalating dosage in psoriatic arthritis gives the same treatment results as standard dosage of adalimumab or etanercept: results from the nationwide Icelandic ICEBIO registry

Directory of Open Access Journals (Sweden)

Gudbjornsson B

2018-05-01

Full Text Available Bjorn Gudbjornsson,1,2 Arni Jon Geirsson,3,4 Niels Steen Krogh5 1Centre for Rheumatology Research, University Hospital, Reykjavik, Iceland; 2Faculty of Medicine, University of Iceland, Reykjavik, Iceland; 3Department of Rheumatology, University Hospital, Reykjavik, Iceland; 4Laeknasetrid - Medical Clinic, University of Iceland, Reykjavik, Iceland; 5Zitelab Aps, Copenhagen, Denmark Objective: To explore differences in response to a low dosage regimen of infliximab with an escalating dosage in comparison to a standard dosage of etanercept and adalimumab in patients with psoriatic arthritis (PsA. Methods: Biologically naïve PsA patients who were beginning anti-TNF-α therapy were selected from the ICEBIO registry. Demographics and clinical differences were compared in four treatment groups: infliximab <4 mg/kg; infliximab >4 mg/kg; etanercept or adalimumab at baseline and on follow-up (6 and 12 months, last visit. The Kruskal–Wallis rank sum test was used for comparison of the groups and the Wilcoxon test to compare the two infliximab dosage regimens. Results: One hundred and eighty-five patients (61% female were identified; 84 patients received infliximab, 66 etanercept, and 35 adalimumab. A total of 19% of the patients treated with infliximab escalated their dosage ≥4 mg/kg. No significant differences were observed at baseline in respect to visual analog scale (VAS pain, VAS fatigue, Health Assessment Questionnaire, C-reactive protein (CRP, numbers of swollen or tender joints, or Disease Activity Score (DAS 28-CRP values. A similar treatment response was observed in all four treatment groups on follow-up. Conclusion: In respect to treatment effects, a low dosage of infliximab with possible escalating dosage is acceptable for the majority of PsA patients who are in need of biological treatment. Keywords: psoriatic arthritis, outcome, biological treatment, routine care, clinical nationwide registry

Determining S-1 dosage at hospitals prioritizing cancer chemotherapy

International Nuclear Information System (INIS)

Morimoto, Shigefumi; Kitada, Noriaki; Anami, Setsuko

2008-01-01

Although it is recommended that the standard S-1 dosage should be based on how large the body surface area is, an on-site setting of the appropriate dosage is often lower than the standard one, depending on the individual's condition and considering possible side effects and so, on. Here, we investigated usage conditions for S-1 as a part of field training for expert pharmacists at our hospital that performs total clinical treatments. Decreases in dosage per day for elderly patients were although the standard dosage is generally determined according to the amount of a patient's body surface. We conducted a retrospective survey with a total 90 patients by creating a tree-diagram to identify a reduction standard. It was found that the S-1 dosage was decreased when there were side effects, aggravation in performance status, decrease in kidney function, old age, combined injection chemotherapy, and a decrease in radiation therapy performance. The dosage decreases without such medical reasons were seen in only 4 of the 90 patients. At hospitals giving priority to chemotherapy, it became clear that appropriate treatment was promoted by decreasing. The individual target dosage on the basis of daily medical examination. (author)

Intelligent system for improving dosage control

Directory of Open Access Journals (Sweden)

Fabio Cosme Rodrigues dos Santos

2017-02-01

Full Text Available Coagulation is one of the most important processes in a drinking-water treatment plant, and it is applied to destabilize impurities in water for the subsequent flocculation stage. Several techniques are currently used in the water industry to determine the best dosage of the coagulant, such as the jar-test method, zeta potential measurements, artificial intelligence methods, comprising neural networks, fuzzy and expert systems, and the combination of the above-mentioned techniques to help operators and engineers in the water treatment process. Current paper presents an artificial neural network approach to evaluate optimum coagulant dosage for various scenarios in raw water quality, using parameters such as raw water color, raw water turbidity, clarified and filtered water turbidity and a calculated Dose Rate to provide the best performance in the filtration process. Another feature in current approach is the use of a backpropagation neural network method to estimate the best coagulant dosage simultaneously at two points of the water treatment plant. Simulation results were compared to the current dosage rate and showed that the proposed system may reduce costs of raw material in water treatment plant.

Evaluation of students' knowledge about paediatric dosage calculations.

Science.gov (United States)

Özyazıcıoğlu, Nurcan; Aydın, Ayla İrem; Sürenler, Semra; Çinar, Hava Gökdere; Yılmaz, Dilek; Arkan, Burcu; Tunç, Gülseren Çıtak

2018-01-01

Medication errors are common and may jeopardize the patient safety. As paediatric dosages are calculated based on the child's age and weight, risk of error in dosage calculations is increasing. In paediatric patients, overdose drug prescribed regardless of the child's weight, age and clinical picture may lead to excessive toxicity and mortalities while low doses may delay the treatment. This study was carried out to evaluate the knowledge of nursing students about paediatric dosage calculations. This research, which is of retrospective type, covers a population consisting of all the 3rd grade students at the bachelor's degree in May, 2015 (148 students). Drug dose calculation questions in exam papers including 3 open ended questions on dosage calculation problems, addressing 5 variables were distributed to the students and their responses were evaluated by the researchers. In the evaluation of the data, figures and percentage distribution were calculated and Spearman correlation analysis was applied. Exam question on the dosage calculation based on child's age, which is the most common method in paediatrics, and which ensures right dosages and drug dilution was answered correctly by 87.1% of the students while 9.5% answered it wrong and 3.4% left it blank. 69.6% of the students was successful in finding the safe dose range, and 79.1% in finding the right ratio/proportion. 65.5% of the answers with regard to Ml/dzy calculation were correct. Moreover, student's four operation skills were assessed and 68.2% of the students were determined to have found the correct answer. When the relation among the questions on medication was examined, a significant relation (correlation) was determined between them. It is seen that in dosage calculations, the students failed mostly in calculating ml/dzy (decimal). This result means that as dosage calculations are based on decimal values, calculations may be ten times erroneous when the decimal point is placed wrongly. Moreover, it

Advances in solid dosage form manufacturing technology.

Science.gov (United States)

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.

Microbial quality of some herbal solid dosage forms

African Journals Online (AJOL)

STORAGESEVER

2010-03-15

Mar 15, 2010 ... Key words: Microbial quality, herbal, contamination, solid dosage form ... The type of dosage form, packaging, manufacturing and expiration dates of subject solid herbal .... According to WHO report (2002), Salmonella food.

21 CFR 520.905 - Fenbendazole oral dosage forms.

Science.gov (United States)

2010-04-01

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

Buccal Dosage Forms: General Considerations for Pediatric Patients.

Science.gov (United States)

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

2017-02-01

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

Gene Duplicability of Core Genes Is Highly Consistent across All Angiosperms.

Science.gov (United States)

Li, Zhen; Defoort, Jonas; Tasdighian, Setareh; Maere, Steven; Van de Peer, Yves; De Smet, Riet

2016-02-01

Gene duplication is an important mechanism for adding to genomic novelty. Hence, which genes undergo duplication and are preserved following duplication is an important question. It has been observed that gene duplicability, or the ability of genes to be retained following duplication, is a nonrandom process, with certain genes being more amenable to survive duplication events than others. Primarily, gene essentiality and the type of duplication (small-scale versus large-scale) have been shown in different species to influence the (long-term) survival of novel genes. However, an overarching view of "gene duplicability" is lacking, mainly due to the fact that previous studies usually focused on individual species and did not account for the influence of genomic context and the time of duplication. Here, we present a large-scale study in which we investigated duplicate retention for 9178 gene families shared between 37 flowering plant species, referred to as angiosperm core gene families. For most gene families, we observe a strikingly consistent pattern of gene duplicability across species, with gene families being either primarily single-copy or multicopy in all species. An intermediate class contains gene families that are often retained in duplicate for periods extending to tens of millions of years after whole-genome duplication, but ultimately appear to be largely restored to singleton status, suggesting that these genes may be dosage balance sensitive. The distinction between single-copy and multicopy gene families is reflected in their functional annotation, with single-copy genes being mainly involved in the maintenance of genome stability and organelle function and multicopy genes in signaling, transport, and metabolism. The intermediate class was overrepresented in regulatory genes, further suggesting that these represent putative dosage-balance-sensitive genes. © 2016 American Society of Plant Biologists. All rights reserved.

Intercavitary implants dosage calculation

International Nuclear Information System (INIS)

Rehder, B.P.

The use of spacial geometry peculiar to each treatment for the attainment of intercavitary and intersticial implants dosage calculation is presented. The study is made in patients with intercavitary implants by applying a modified Manchester technique [pt

21 CFR 522.1660 - Oxytetracycline injectable dosage forms.

Science.gov (United States)

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. ...

Radiation dosage

Energy Technology Data Exchange (ETDEWEB)

Finston, Roland [Health Physics, Stanford University, Stanford, CA (United States)

1986-07-01

Radiation dosage at Bikini Atoll is the result of current soil contamination, a relic of the nuclear weapons testing program of some 30 years ago. The principal contaminants today and some of their physical properties are listed: cesium-137, strontium-90, plutonium -239, 240 and americium-241. Cobalt-60 contributes less than 1 to the dose and is not considered significant. A resident of the atoll would accumulate radiation dose (rem) in two ways -- by exposure to radiation emanating from the ground and vegetation, and by exposure to radiation released in the spontaneous decay of radionuclides that have entered his body during the ingestion of locally grown foods. The latter process would account for some 90% of the dose; cesium-137 would be responsible for 0 90% of it. Since BARC's method of estimating dosage differs in some respects from that employed by the Lawrence Livermore National Laboratory (LLNL), (Ref.1, LLNL 1982) we are presenting our method in detail. The differences have two sources. First, the numbers used by BARC for the daily ingestion of radionuclides via the diet are higher than LLNL's. Second, BARC's calculation of dose from radionuclide intake utilizes the ICRP system. The net result is that BARC doses are consistently higher than LLNL doses, and in this respect are more conservative.

Radiation dosage

International Nuclear Information System (INIS)

Finston, Roland

1986-01-01

Radiation dosage at Bikini Atoll is the result of current soil contamination, a relic of the nuclear weapons testing program of some 30 years ago. The principal contaminants today and some of their physical properties are listed: cesium-137, strontium-90, plutonium -239, 240 and americium-241. Cobalt-60 contributes less than 1 to the dose and is not considered significant. A resident of the atoll would accumulate radiation dose (rem) in two ways -- by exposure to radiation emanating from the ground and vegetation, and by exposure to radiation released in the spontaneous decay of radionuclides that have entered his body during the ingestion of locally grown foods. The latter process would account for some 90% of the dose; cesium-137 would be responsible for 0 90% of it. Since BARC's method of estimating dosage differs in some respects from that employed by the Lawrence Livermore National Laboratory (LLNL), (Ref.1, LLNL 1982) we are presenting our method in detail. The differences have two sources. First, the numbers used by BARC for the daily ingestion of radionuclides via the diet are higher than LLNL's. Second, BARC's calculation of dose from radionuclide intake utilizes the ICRP system. The net result is that BARC doses are consistently higher than LLNL doses, and in this respect are more conservative

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

Science.gov (United States)

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

2015-12-01

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

Radiation dosage of various CT-methods in lung diagnostics

International Nuclear Information System (INIS)

Heinz-Peer, G.; Weninger, F.; Nowotny, R.; Herold, C.J.

1996-01-01

Introduction of the computed tomography index CTDI and the multiple scan average dose (MSAD) has led to standardization of the dose description in CT examinations. Despite the use of these dose parameters, many different dosages are reported in the literature for different CT methods. In addition, there is still a wide range of radiation dosimetry results reported for conventional CT, helical CT, and HRCT used in chest examinations. The variations in dosage are mainly due to difference in factors affecting the dose, i.e. beam geometry, beam quality, scanner geometry ('generation'), and operating parameters. In addition, CT dosimetry instrumentation and methodology make a contribution to dosages. Recent studies calculating differences in factors affecting dosage and CT dosimetry and using similar operating parameters, show similar results in CT dosimetry for conventional and helical CT. On the other hand, dosages for HRCT were greatly reduced. This was mainly caused by narrow beam collimation and increasing section spacing. (orig.) [de

Hydraulic Modular Dosaging Systems for Machine Drives

Directory of Open Access Journals (Sweden)

A. J. Kotlobai

2005-01-01

Full Text Available The justified principle of making modular dosaging systems for positive-displacement multimotor hydraulic drives used in running gear and technological equipment of mobile construction, road and agricultural machines makes it possible to synchronize motion of running parts. The examples of the realization of modular dosaging systems and an algorithm of their operation are given in the paper.

Sex chromosome-specific regulation in the Drosophila male germline but little evidence for chromosomal dosage compensation or meiotic inactivation.

Directory of Open Access Journals (Sweden)

Colin D Meiklejohn

2011-08-01

Full Text Available The evolution of heteromorphic sex chromosomes (e.g., XY in males or ZW in females has repeatedly elicited the evolution of two kinds of chromosome-specific regulation: dosage compensation--the equalization of X chromosome gene expression in males and females--and meiotic sex chromosome inactivation (MSCI--the transcriptional silencing and heterochromatinization of the X during meiosis in the male (or Z in the female germline. How the X chromosome is regulated in the Drosophila melanogaster male germline is unclear. Here we report three new findings concerning gene expression from the X in Drosophila testes. First, X chromosome-wide dosage compensation appears to be absent from most of the Drosophila male germline. Second, microarray analysis provides no evidence for X chromosome-specific inactivation during meiosis. Third, we confirm the previous discovery that the expression of transgene reporters driven by autosomal spermatogenesis-specific promoters is strongly reduced when inserted on the X chromosome versus the autosomes; but we show that this chromosomal difference in expression is established in premeiotic cells and persists in meiotic cells. The magnitude of the X-autosome difference in transgene expression cannot be explained by the absence of dosage compensation, suggesting that a previously unrecognized mechanism limits expression from the X during spermatogenesis in Drosophila. These findings help to resolve several previously conflicting reports and have implications for patterns of genome evolution and speciation in Drosophila.

Gene Duplicability of Core Genes Is Highly Consistent across All Angiosperms[OPEN

Science.gov (United States)

Li, Zhen; Van de Peer, Yves; De Smet, Riet

2016-01-01

Gene duplication is an important mechanism for adding to genomic novelty. Hence, which genes undergo duplication and are preserved following duplication is an important question. It has been observed that gene duplicability, or the ability of genes to be retained following duplication, is a nonrandom process, with certain genes being more amenable to survive duplication events than others. Primarily, gene essentiality and the type of duplication (small-scale versus large-scale) have been shown in different species to influence the (long-term) survival of novel genes. However, an overarching view of “gene duplicability” is lacking, mainly due to the fact that previous studies usually focused on individual species and did not account for the influence of genomic context and the time of duplication. Here, we present a large-scale study in which we investigated duplicate retention for 9178 gene families shared between 37 flowering plant species, referred to as angiosperm core gene families. For most gene families, we observe a strikingly consistent pattern of gene duplicability across species, with gene families being either primarily single-copy or multicopy in all species. An intermediate class contains gene families that are often retained in duplicate for periods extending to tens of millions of years after whole-genome duplication, but ultimately appear to be largely restored to singleton status, suggesting that these genes may be dosage balance sensitive. The distinction between single-copy and multicopy gene families is reflected in their functional annotation, with single-copy genes being mainly involved in the maintenance of genome stability and organelle function and multicopy genes in signaling, transport, and metabolism. The intermediate class was overrepresented in regulatory genes, further suggesting that these represent putative dosage-balance-sensitive genes. PMID:26744215

21 CFR 526.1696 - Penicillin intramammary dosage forms.

Science.gov (United States)

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 Penicillin...

21 CFR 520.1696 - Penicillin oral dosage forms.

Science.gov (United States)

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 oral...

21 CFR 520.45 - Albendazole oral dosage forms.

Science.gov (United States)

2010-04-01

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

[Gene polymorphism of CYP450 2C9 and VKORC1 in Chinese population and their relationships to the maintaining dosage of warfarin].

Science.gov (United States)

Zhang, Ya-nan; Cui, Wei; Han, Mei; Zheng, Bin; Liu, Fan; Xie, Rui-qin; Yang, Xiao-hong; Gu, Guo-qiang; Zheng, Hong-mei; Wen, Jin-kun

2010-02-01

To investigate the distribution of gene polymorphism of CYP450 2C9 and VKORC1-1639A/G in the Chinese population as well as the difference of genetic polymorphism between Chinese Han population and other ethnic populations. Contribution of CYP2C9 and VKORC1 genotype to the maintenance doses on warfarin was also studied. The genotype and allele frequencies were calculated and compared with those in other populations. One hundred and one patients with stable anticoagulation with warfarin under a target international normalized ratio (INR) of 2.0 to 3.0 were enrolled for studying the relationship between the CYP2C9 and VKORC1 gene polymorphism and the warfarin maintaining dosage. CYP450 2C9*3 + 1075C/A allele frequencies were:AA in 449 cases (92.2%), AC in 36 cases (7.4%) and CC in 2 cases (0.4%), respectively. VKORC1 -1639A/G allele frequencies were AA in 415 cases (85.2%), GA in 72 cases (14.8%), but GG in no case (0.0%), respectively. When linear stepwise regression analysis was used to identify factors contributing to warfarin stable dose, the final equation was: ln (D) = 0.346 + 0.017 (weight) - 0.376 (CYP450 2C9*3 + 1075C/A) + 0.148 (VKORC1-1639A/G) - 0.002 (age) (r = 0.827, P = 0.02). There existed significant gene polymorphism CYP450 2C9*3 + 1075C/A and VKORC1-1639A/G in the Chinese Han population. Both Gene polymorphisms of CYP450 2C9*3 + 1075C/A and VKORC1-1639A/G were significantly affecting the maintaining dose of warfarin in the Chinese population.

21 CFR 524.1662 - Oxytetracycline hydrochloride ophthalmic and topical dosage forms.

Science.gov (United States)

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. ...

X-chromosome gene dosage as a determinant of impaired pre and postnatal growth and adult height in Turner syndrome.

Science.gov (United States)

Fiot, Elodie; Zenaty, Delphine; Boizeau, Priscilla; Haigneré, Jeremy; Dos Santos, Sophie; Léger, Juliane

2016-03-01

Short stature is a key aspect of the phenotype of patients with Turner syndrome (TS). SHOX haploinsufficiency is responsible for about two-thirds of the height deficit. The aim was to investigate the effect of X-chromosome gene dosage on anthropometric parameters at birth, spontaneous height, and adult height (AH) after growth hormone (GH) treatment. We conducted a national observational multicenter study. Birth parameter SDS for gestational age, height, and AH before and after GH treatment respectively, and height deficit with respect to target height (SDS) were classified by karyotype subgroup in a cohort of 1501 patients with TS: 45,X (36%), isoXq (19%), 45,X/46,XX (15%), XrX (7%), presence of Y (6%), or other karyotypes (17%). Birth weight, length (P<0.0001), and head circumference (P<0.001), height and height deficit with respect to target height (SDS) before GH treatment, at a median age of 8.8 (5.3-11.8) years and after adjustment for age and correction for multiple testing (P<0.0001), and AH deficit with respect to target height at a median age of 19.3 (18.0-21.8) years and with additional adjustment for dose and duration of GH treatment (P=0.006), were significantly associated with karyotype subgroup. Growth retardation tended to be more severe in patients with XrX, isoXq, and, to a lesser extent, 45,X karyotypes than in patients with 45,X/46,XX karyotypes or a Y chromosome. These data suggest that haploinsufficiency for an unknown Xp gene increases the risk of fetal and postnatal growth deficit and short AH with respect to target height after GH therapy. © 2016 European Society of Endocrinology.

21 CFR 522.1222 - Ketamine hydrochloride injectable dosage forms.

Science.gov (United States)

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. ...

Investigation of contrast agent dosage for perfusion-weighted MRI

International Nuclear Information System (INIS)

Erb, G.; Benner, T.; Heiland, S.; Reith, W.; Sartor, K.; Forsting, M.

1997-01-01

Purpose: In this study we investigated, whether increasing the dosage of a paramagnetic contrast agent results in a stronger signal decrease in T 2 *-weighted perfusion sequences and therefore more meaningful parameter maps. Material and methods: In a prospective study bolus injection of gadolinium-DTPA was performed at dosages of 0.1, 0.2, and 0.3 mmol/kg body weight (BW) in 10 patients each. Before, during and after bolus injection 40 T 2 *-weighted images of a reference brain slice were acquired within 65.6 seconds on a 1.0 T clinical scanner and perfusion parameters were calculated. Results: Due to the limited signal decrease during bolus passage and the resulting low signal-difference-to-noise ratio (ΔS/N) no reliable differentiation of gray and white matter was possible at a contrast agent dosage of 0.1 mmol/kg BW. Only at higher dosages, both, signal decrease and ΔS/N were strong enough to allow differentiation of gray and white matter and to yield reliable parameter maps. Conclusion: For meaningful MR perfusion imaging at 1.0 T and with the given sequence a contrast agent dosage of at least 0.2 mmol/kg BW is necessary, if a 0.5-molar contrast agent is used. (orig.) [de

Dosage of boron traces in graphite, uranium and beryllium oxide; Dosage de traces de bore dans le graphite, l'uranium et l'oxyde de beryllium

Energy Technology Data Exchange (ETDEWEB)

Coursier, J [Ecole Nationale Superieure de Physique et Chimie Industrielles, 75 - Paris (France); Hure, J; Platzer, R [Commissariat a l' Energie Atomique, Saclay (France). Centre d' Etudes Nucleaires

1955-07-01

The problem of the dosage of the boron in the materials serving to the construction of nuclear reactors arises of the following way: to determine to about 0,1 ppm close to the quantities of boron of the order of tenth ppm. We have chosen the colorimetric analysis with curcumin as method of dosage. To reach the indicated contents, it is necessary to do a previous separation of the boron and the materials of basis, either by extraction of tetraphenylarsonium fluoborate in the case of the boron dosage in uranium and the beryllium oxide, either by the use of a cations exchanger resin of in the case of graphite. (M.B.) [French] Le probleme du dosage du bore dans les materiaux servant a la construction de reacteurs nucleaires se pose de la facon suivante: determiner a environ 0,1 ppm pres des quantites de bore de l'ordre de quelques dixiemes de ppm. Nous avons choisit la colorimetrie a la curcumine comme methode de dosage. Pour atteindre les teneurs indiquees, il est necessaire d'effectuer une separation prealable du bore et des materiaux de base, soit par extraction du fluoborate de tetraphenylarsonium dans le cas du dosage de bore dans l'uranium et l'oxyde de beryllium, soit par l'utilisation d'une resine echangeuse de cations dans le cas du graphite. (M.B.)

Dosage compensation of serine-4 transfer RNA in Drosophila melanogaster

International Nuclear Information System (INIS)

Birchler, J.A.; Owenby, R.K.; Jacobson, K.B.

1982-01-01

A dosage series of the X chromosome site for serine-4 transfer RNA consisting of one of three copies in females and one to two in males was constructed to test whether transfer RNA expression is governed by dosage compensation. A dosage effect on the level of the serine-4 isoacceptor was observed in both females and males when the structural locus was varied. However, in males, each dose had a relatively greater expression so the normal one dose was slightly greater than the total female value and the duplicated male had the highest relative expression of all the types examined. Serine-4 levels in males and females from an isogenic Oregon-R stock were similar. Thus the transfer RNA levels conform to the expectations of dosage compensation

Semi-solid dosage form of clonazepam for rapid oral mucosal absorption.

Science.gov (United States)

Sakata, Osamu; Machida, Yoshiharu; Onishi, Hiraku

2011-07-01

In order to obtain an alternative to the intravenous (i.v.) dosage form of clonazepam (CZ), an oral droplet formulation of CZ was developed previously; however, the droplet was physically unstable. Therefore, in the present study, it was attempted to develop an easily-handled dosage form, which was more physically stable and allowed rapid drug absorption from oral mucosa. A semi-solid dosage form, composed of polyethylene glycol 1500 (PEG), CZ, and oleic acid (OA) at 37/1/2 (w/w) and named PEG/CZ/OA, and a semi-solid dosage form containing PEG and CZ at 39/1 (w/w), called PEG/CZ, were prepared. Their physical stability in air at room temperature and oral mucosal absorption in rats were investigated. The semi-solid dosage forms were much more stable physically than the droplet, that is, no recrystallization of CZ was observed for at least 8 days. The effective concentration for humans and rats (20 ng/mL or more) was achieved within 30 min after buccal administration for both PEG/CZ/OA and PEG/CZ. The plasma concentration increased gradually and less varied at each time point for PEG/CZ/OA. PEG/CZ/OA was found to show more rapid and higher absorption of CZ in buccal administration than in sublingual administration. Buccal administration with the semi-solid dosage PEG/CZ with or without OA was suggested to be a possibly useful novel dosage form as an alternative to i.v. injection.

Evaluation of insecticides in different dosages to control cicadas in parica plantations

Directory of Open Access Journals (Sweden)

Odineila Martins Monteiro

2014-07-01

Full Text Available This study aimed to determine the more efficient and economically viable dosage of chemical insecticide to control Quesada gigas (Hemiptera: Cicadidae nymphs in parica plantations. Three dosages of three products (carbofuran, imidacloprid and thiamethoxam were tested based on the maximum recommended dosage for the control of cicadas in coffee plants and applied in total area. The dosage of one kilogram of a commercial product based in thiamethoxam per hectare was more efficient economically and environmentally to control nymphs of Q. gigas in parica plantations.

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

Science.gov (United States)

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. ...

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

Science.gov (United States)

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 drug...

Automatic identification and normalization of dosage forms in drug monographs

Science.gov (United States)

2012-01-01

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

Evaluation of the effect of torsemide on warfarin dosage requirements.

Science.gov (United States)

Lai, Sophia; Momper, Jeremiah D; Yam, Felix K

2017-08-01

Background According to drug interaction databases, torsemide may potentiate the effects of warfarin. Evidence for this drug-drug interaction, however, is conflicting and the clinical significance is unknown. Objective The aim of this study is to evaluate the impact of torsemide initiation on warfarin dosage requirements. Setting This study was conducted at the Veterans Affairs Healthcare System in San Diego, California. Method A retrospective cohort study was conducted using Veterans Affairs data from patients who were converted from bumetanide to torsemide between March 2014 and July 2014. Patients were also prescribed and taking warfarin during the observation period. Warfarin dosage requirements were evaluated to determine if any changes occurred within the first 3 months of starting torsemide. Main outcome measure The primary outcome was the average weekly warfarin dose before and after torsemide initiation. Results Eighteen patients met study inclusion criteria. The weekly warfarin dose before and after initiation of torsemide was not significantly different (34 ± 15 and 34 ± 13 mg, p > 0.05). Of those eighteen patients, only two experienced elevations in INR that required a decrease in warfarin dosage after torsemide initiation. Between those two patients, dosage reductions ranged from 5.3 to 18%. Conclusion These results indicated that most patients did not require any warfarin dosage adjustments after torsemide was initiated. The potential for interaction, however, still exists. While empiric warfarin dosage adjustments are not recommended when initiating torsemide, increased monitoring is warranted to minimize the risk of adverse effects.

Weird mammals provide insights into the evolution of mammalian sex chromosomes and dosage compensation.

Science.gov (United States)

Graves, Jennifer A Marshall

2015-12-01

The deep divergence of mammalian groups 166 and 190 million years ago (MYA) provide genetic variation to explore the evolution of DNA sequence, gene arrangement and regulation of gene expression in mammals. With encouragement from the founder of the field, Mary Lyon, techniques in cytogenetics and molecular biology were progressively adapted to characterize the sex chromosomes of kangaroos and other marsupials, platypus and echidna-and weird rodent species. Comparative gene mapping reveals the process of sex chromosome evolution from their inception 190 MYA (they are autosomal in platypus) to their inevitable end (the Y has disappeared in two rodent lineages). Our X and Y are relatively young, getting their start with the evolution of the sex-determining SRY gene, which triggered progressive degradation of the Y chromosome. Even more recently, sex chromosomes of placental mammals fused with an autosomal region which now makes up most of the Y. Exploration of gene activity patterns over four decades showed that dosage compensation via X-chromosome inactivation is unique to therian mammals, and that this whole chromosome control process is different in marsupials and absent in monotremes and reptiles, and birds. These differences can be exploited to deduce how mammalian sex chromosomes and epigenetic silencing evolved.

Dose-related gene expression changes in forebrain following acute, low-level chlorpyrifos exposure in neonatal rats

International Nuclear Information System (INIS)

Ray, Anamika; Liu Jing; Ayoubi, Patricia; Pope, Carey

2010-01-01

Chlorpyrifos (CPF) is a widely used organophosphorus insecticide (OP) and putative developmental neurotoxicant in humans. The acute toxicity of CPF is elicited by acetylcholinesterase (AChE) inhibition. We characterized dose-related (0.1, 0.5, 1 and 2 mg/kg) gene expression profiles and changes in cell signaling pathways 24 h following acute CPF exposure in 7-day-old rats. Microarray experiments indicated that approximately 9% of the 44,000 genes were differentially expressed following either one of the four CPF dosages studied (546, 505, 522, and 3,066 genes with 0.1, 0.5, 1.0 and 2.0 mg/kg CPF). Genes were grouped according to dose-related expression patterns using K-means clustering while gene networks and canonical pathways were evaluated using Ingenuity Pathway Analysis (registered) . Twenty clusters were identified and differential expression of selected genes was verified by RT-PCR. The four largest clusters (each containing from 276 to 905 genes) constituted over 50% of all differentially expressed genes and exhibited up-regulation following exposure to the highest dosage (2 mg/kg CPF). The total number of gene networks affected by CPF also rose sharply with the highest dosage of CPF (18, 16, 18 and 50 with 0.1, 0.5, 1 and 2 mg/kg CPF). Forebrain cholinesterase (ChE) activity was significantly reduced (26%) only in the highest dosage group. Based on magnitude of dose-related changes in differentially expressed genes, relative numbers of gene clusters and signaling networks affected, and forebrain ChE inhibition only at 2 mg/kg CPF, we focused subsequent analyses on this treatment group. Six canonical pathways were identified that were significantly affected by 2 mg/kg CPF (MAPK, oxidative stress, NFΚB, mitochondrial dysfunction, arylhydrocarbon receptor and adrenergic receptor signaling). Evaluation of different cellular functions of the differentially expressed genes suggested changes related to olfactory receptors, cell adhesion/migration, synapse

Application of DBNPA dosage for biofouling control in spiral wound membrane systems

KAUST Repository

Siddiqui, Amber

2017-05-30

Biocides may be used to control biofouling in spiral-wound reverse osmosis (RO) and nanofiltration (NF) systems. The objective of this study was to investigate the effect of biocide 2,2-dibromo-3-ni-trilopropionamide (DBNPA) dosage on biofouling control. Preventive biofouling control was studied applying a continuous dosage of substrate (0.5 mg/L) and DBNPA (1 mg/L). Curative biofouling control was studied on pre-grown biofilms, once again applying a continuous dosage of substrate (0.5 mg acetate C/L) and DBNPA (1 and 20 mg/L). Biofouling studies were performed in membrane fouling simulators (MFSs) supplied with biodegradable substrate and DBNPA. The pressure drop was monitored in time and at the end of the study, the accumulated biomass in MFS was quantified by adenosine triphosphate (ATP) and total organic carbon (TOC) analysis. Continuous dosage of DBNPA (1 mg/L) prevented pressure drop increase and biofilm accumulation in the MFSs during a run time of 7 d, showing that biofouling can be managed by preventive DBNPA dosage. For biofouled systems, continuous dosage of DBNPA (1 and 20 mg/L) inactivated the accumulated biomass but did not restore the original pressure drop and did not remove the accumulated inactive cells and extracellular polymeric substances (EPS), indicating DBNPA dosage is not suitable for curative biofouling control.

Quality of 'Climax' blueberries after low dosage electron beam irradiation

International Nuclear Information System (INIS)

Miller, W.R.; McDonald, R.E.; McCollum, T.G.; Smittle, B.J.

1994-01-01

Fruit of 'Climax' rabbiteye blueberries (Vaccinium ashei Reade) were irradiated by a linear accelerator at 0, 0.25, 0.5, 0.75, 1.0, and 1.25 kGy and evaluated for various quality attributes after storage for 1, 3, 7, or 14 days at 1C plus 2 days at 15C, respectively. Weight loss increased during storage and averaged 4.2% after the final inspection and was not affected by irradiation dosage. About 5% of total berries were decayed after 14 days at 1C, about 6% after the final inspection at 15C, but decay was not affected by the level of irradiation. Electrolyte leakage, skin color, total soluble solids, acidity, and pH were also not affected by irradiation dosage. There was a significant decline in berry firmness, flavor, and texture as dosage increased. Berries treated at 1.0 kGy or above were softer and had lower flavor and texture preference scores than berries treated at lower dosages or nontreated berries

C. elegans FOG-3/Tob can either promote or inhibit germline proliferation, depending on gene dosage and genetic context.

Science.gov (United States)

Snow, J J; Lee, M-H; Verheyden, J; Kroll-Conner, P L; Kimble, J

2013-05-23

Vertebrate Tob/BTG proteins inhibit cell proliferation when overexpressed in tissue-culture cells, and they can function as tumor suppressors in mice. The single Caenorhabditis elegans Tob/BTG ortholog, FOG-3, by contrast, was identified from its loss-of-function phenotype as a regulator of sperm fate specification. Here we report that FOG-3 also regulates proliferation in the germline tissue. We first demonstrate that FOG-3 is a positive regulator of germline proliferation. Thus, fog-3 null mutants possess fewer germ cells than normal, a modest but reproducible decrease observed for each of two distinct fog-3 null alleles. A similar decrease also occurred in fog-3/+ heterozygotes, again for both fog-3 alleles, revealing a haplo-insufficient effect on proliferation. Therefore, FOG-3 normally promotes proliferation, and two copies of the fog-3 gene are required for this function. We next overexpressed FOG-3 by removal of FBF, the collective term for FBF-1 and FBF-2, two nearly identical PUF RNA-binding proteins. We find that overexpressed FOG-3 blocks proliferation in fbf-1 fbf-2 mutants; whereas germ cells stop dividing and instead differentiate in fbf-1 fbf-2 double mutants, they continue to proliferate in fog-3; fbf-1 fbf-2 triple mutants. Therefore, like its vertebrate Tob/BTG cousins, overexpressed FOG-3 is 'antiproliferative'. Indeed, some fog-3; fbf-1 fbf-2 mutants possess small tumors, suggesting that FOG-3 can act as a tumor suppressor. Finally, we show that FOG-3 and FBF work together to promote tumor formation in animals carrying oncogenic Notch mutations. A similar effect was not observed when germline tumors were induced by manipulation of other regulators; therefore, this FOG-3 tumor-promoting effect is context dependent. We conclude that FOG-3 can either promote or inhibit proliferation in a manner that is sensitive to both genetic context and gene dosage. The discovery of these FOG-3 effects on proliferation has implications for our understanding of

Doubled dosage of sofosbuviris expected for inhibiting Zika virus infection

Institute of Scientific and Technical Information of China (English)

Somsri Wiwanitkit; Viroj Wiwanitkit

2017-01-01

Sofosbuvir is a new antiviral drug that has been recommended for management of hepatitis C virus (HCV) for a few years. New researches support that sofosbuvir might be useful for the management of Zika virus infection. Based on the pharmacological activity, inhibiting the HCV RNA-dependent RNA polymerase (RdRp or NS5 protein), sofosbuvir is proposed for its effectiveness against Zika virus infection. Here, the authors used a mathematical modelling theoretical approach to predict the expected dosage of sofosbuvir for inhibiting Zika virus infection. Based on the modeling study, if sofosbuvir is assigned for management of Zika virus infection, doubled dosage of the present dosage for hepatitis C management is recommended.

Dosage of boron traces in graphite, uranium and beryllium oxide

International Nuclear Information System (INIS)

Coursier, J.; Hure, J.; Platzer, R.

1955-01-01

The problem of the dosage of the boron in the materials serving to the construction of nuclear reactors arises of the following way: to determine to about 0,1 ppm close to the quantities of boron of the order of tenth ppm. We have chosen the colorimetric analysis with curcumin as method of dosage. To reach the indicated contents, it is necessary to do a previous separation of the boron and the materials of basis, either by extraction of tetraphenylarsonium fluoborate in the case of the boron dosage in uranium and the beryllium oxide, either by the use of a cations exchanger resin of in the case of graphite. (M.B.) [fr

TaS2 nanosheet-based room-temperature dosage meter for nitric oxide

Directory of Open Access Journals (Sweden)

Qiyuan He

2014-09-01

Full Text Available A miniature dosage meter for toxic gas is developed based on TaS2 nanosheets, which is capable of indicating the toxic dosage of trace level NO at room temperature. The TaS2 film-based chemiresistor shows an irreversible current response against the exposure of NO. The unique non-recovery characteristic makes the TaS2 film-based device an ideal indicator of total dosage of chronicle exposure.

Avian sex, sex chromosomes, and dosage compensation in the age of genomics.

Science.gov (United States)

Graves, Jennifer A Marshall

2014-04-01

Comparisons of the sex chromosome systems in birds and mammals are widening our view and deepening our understanding of vertebrate sex chromosome organization, function, and evolution. Birds have a very conserved ZW system of sex determination in which males have two copies of a large, gene-rich Z chromosome, and females have a single Z and a female-specific W chromosome. The avian ZW system is quite the reverse of the well-studied mammalian XY chromosome system, and evolved independently from different autosomal blocs. Despite the different gene content of mammal and bird sex chromosomes, there are many parallels. Genes on the bird Z and the mammal X have both undergone selection for male-advantage functions, and there has been amplification of male-advantage genes and accumulation of LINEs. The bird W and mammal Y have both undergone extensive degradation, but some birds retain early stages and some mammals terminal stages of the process, suggesting that the process is more advanced in mammals. Different sex-determining genes, DMRT1 and SRY, define the ZW and XY systems, but DMRT1 is involved in downstream events in mammals. Birds show strong cell autonomous specification of somatic sex differences in ZZ and ZW tissue, but there is growing evidence for direct X chromosome effects on sexual phenotype in mammals. Dosage compensation in birds appears to be phenotypically and molecularly quite different from X inactivation, being partial and gene-specific, but both systems use tools from the same molecular toolbox and there are some signs that galliform birds represent an early stage in the evolution of a coordinated system.

Pavor nocturnus: a complication of single daily tricyclic or neuroleptic dosage.

Science.gov (United States)

Flemenbaum, A

1976-05-01

The author tested the hypothesis that a single bedtime dosage schedule of tricyclic or neuroleptic medication produces increased frequency of night terrors by administering a questionnaire to 30 medical patients who were not receiving such medications and 100 psychiatric patients on either multiple- or single-dosage schedules. Psychiatric patients on multiple-dosage schedules reported no more frightening dreams than the medical patients, whereas almost three-fourths of those receiving single bedtime doses had frightening dreams, a significant difference from the medical sample. This preliminary report is presented to call attention to the possible undesirable effects of a single dose schedule.

Identification of imprinted genes subject to parent-of-origin specific expression in Arabidopsis thaliana seeds.

NARCIS (Netherlands)

Mckeown, P.C.; Laouielle-Duprat, S.; Prins, J.C.P.; Wolff, de P.; Schmid, M.W.; Donoghue, M.T.; Fort, A.; Duszynska, D.; Comte, A.; Lao, N.T.; Wennblom, T.J.; Smant, G.; Köhler, C.; Grossniklaus, U.; Spillane, C.

2011-01-01

Background: Epigenetic regulation of gene dosage by genomic imprinting of some autosomal genes facilitates normal reproductive development in both mammals and flowering plants. While many imprinted genes have been identified and intensively studied in mammals, smaller numbers have been characterized

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

Science.gov (United States)

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 injectable...

Dosage of the Abcg1-U2af1 region modifies locomotor and cognitive deficits observed in the Tc1 mouse model of Down syndrome.

Directory of Open Access Journals (Sweden)

Damien Marechal

Full Text Available Down syndrome (DS results from one extra copy of human chromosome 21 and leads to several alterations including intellectual disabilities and locomotor defects. The transchromosomic Tc1 mouse model carrying an extra freely-segregating copy of human chromosome 21 was developed to better characterize the relation between genotype and phenotype in DS. The Tc1 mouse exhibits several locomotor and cognitive deficits related to DS. In this report we analyzed the contribution of the genetic dosage of 13 conserved mouse genes located between Abcg1 and U2af1, in the telomeric part of Hsa21. We used the Ms2Yah model carrying a deletion of the corresponding interval in the mouse genome to rescue gene dosage in the Tc1/Ms2Yah compound mice to determine how the different behavioral phenotypes are affected. We detected subtle changes with the Tc1/Ms2Yah mice performing better than the Tc1 individuals in the reversal paradigm of the Morris water maze. We also found that Tc1/Ms2Yah compound mutants performed better in the rotarod than the Tc1 mice. This data support the impact of genes from the Abcg1-U2af1 region as modifiers of Tc1-dependent memory and locomotor phenotypes. Our results emphasize the complex interactions between triplicated genes inducing DS features.

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

Science.gov (United States)

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. Copyright © 2016 Elsevier B.V. All rights reserved.

Neural expression and post-transcriptional dosage compensation of the steroid metabolic enzyme 17β-HSD type 4

Directory of Open Access Journals (Sweden)

Wise Petra M

2010-04-01

Full Text Available Abstract Background Steroids affect many tissues, including the brain. In the zebra finch, the estrogenic steroid estradiol (E2 is especially effective at promoting growth of the neural circuit specialized for song. In this species, only the males sing and they have a much larger and more interconnected song circuit than females. Thus, it was surprising that the gene for 17β-hydroxysteroid dehydrogenase type 4 (HSD17B4, an enzyme that converts E2 to a less potent estrogen, had been mapped to the Z sex chromosome. As a consequence, it was likely that HSD17B4 was differentially expressed in males (ZZ and females (ZW because dosage compensation of Z chromosome genes is incomplete in birds. If a higher abundance of HSD17B4 mRNA in males than females was translated into functional enzyme in the brain, then contrary to expectation, males could produce less E2 in their brains than females. Results Here, we used molecular and biochemical techniques to confirm the HSD17B4 Z chromosome location in the zebra finch and to determine that HSD17B4 mRNA and activity were detectable in the early developing and adult brain. As expected, HSD17B4 mRNA expression levels were higher in males compared to females. This provides further evidence of the incomplete Z chromosome inactivation mechanisms in birds. We detected HSD17B4 mRNA in regions that suggested a role for this enzyme in the early organization and adult function of song nuclei. We did not, however, detect significant sex differences in HSD17B4 activity levels in the adult brain. Conclusions Our results demonstrate that the HSD17B4 gene is expressed and active in the zebra finch brain as an E2 metabolizing enzyme, but that dosage compensation of this Z-linked gene may occur via post-transcriptional mechanisms.

Reduced Erg Dosage Impairs Survival of Hematopoietic Stem and Progenitor Cells.

Science.gov (United States)

Xie, Ying; Koch, Mia Lee; Zhang, Xin; Hamblen, Melanie J; Godinho, Frank J; Fujiwara, Yuko; Xie, Huafeng; Klusmann, Jan-Henning; Orkin, Stuart H; Li, Zhe

2017-07-01

ERG, an ETS family transcription factor frequently overexpressed in human leukemia, has been implicated as a key regulator of hematopoietic stem cells. However, how ERG controls normal hematopoiesis, particularly at the stem and progenitor cell level, and how it contributes to leukemogenesis remain incompletely understood. Using homologous recombination, we generated an Erg knockdown allele (Erg kd ) in which Erg expression can be conditionally restored by Cre recombinase. Erg kd/kd animals die at E10.5-E11.5 due to defects in endothelial and hematopoietic cells, but can be completely rescued by Tie2-Cre-mediated restoration of Erg in these cells. In Erg kd/+ mice, ∼40% reduction in Erg dosage perturbs both fetal liver and bone marrow hematopoiesis by reducing the numbers of Lin - Sca-1 + c-Kit + (LSK) hematopoietic stem and progenitor cells (HSPCs) and megakaryocytic progenitors. By genetic mosaic analysis, we find that Erg-restored HSPCs outcompete Erg kd/+ HSPCs for contribution to adult hematopoiesis in vivo. This defect is in part due to increased apoptosis of HSPCs with reduced Erg dosage, a phenotype that becomes more drastic during 5-FU-induced stress hematopoiesis. Expression analysis reveals that reduced Erg expression leads to changes in expression of a subset of ERG target genes involved in regulating survival of HSPCs, including increased expression of a pro-apoptotic regulator Bcl2l11 (Bim) and reduced expression of Jun. Collectively, our data demonstrate that ERG controls survival of HSPCs, a property that may be used by leukemic cells. Stem Cells 2017;35:1773-1785. © 2017 AlphaMed Press.

Synergistic interactions between Drosophila orthologues of genes spanned by de novo human CNVs support multiple-hit models of autism.

Science.gov (United States)

Grice, Stuart J; Liu, Ji-Long; Webber, Caleb

2015-03-01

Autism spectrum disorders (ASDs) are highly heritable and characterised by deficits in social interaction and communication, as well as restricted and repetitive behaviours. Although a number of highly penetrant ASD gene variants have been identified, there is growing evidence to support a causal role for combinatorial effects arising from the contributions of multiple loci. By examining synaptic and circadian neurological phenotypes resulting from the dosage variants of unique human:fly orthologues in Drosophila, we observe numerous synergistic interactions between pairs of informatically-identified candidate genes whose orthologues are jointly affected by large de novo copy number variants (CNVs). These CNVs were found in the genomes of individuals with autism, including a patient carrying a 22q11.2 deletion. We first demonstrate that dosage alterations of the unique Drosophila orthologues of candidate genes from de novo CNVs that harbour only a single candidate gene display neurological defects similar to those previously reported in Drosophila models of ASD-associated variants. We then considered pairwise dosage changes within the set of orthologues of candidate genes that were affected by the same single human de novo CNV. For three of four CNVs with complete orthologous relationships, we observed significant synergistic effects following the simultaneous dosage change of gene pairs drawn from a single CNV. The phenotypic variation observed at the Drosophila synapse that results from these interacting genetic variants supports a concordant phenotypic outcome across all interacting gene pairs following the direction of human gene copy number change. We observe both specificity and transitivity between interactors, both within and between CNV candidate gene sets, supporting shared and distinct genetic aetiologies. We then show that different interactions affect divergent synaptic processes, demonstrating distinct molecular aetiologies. Our study illustrates

Short-time, high-dosage penicillin infusion therapy of syphilis

DEFF Research Database (Denmark)

Lomholt, Hans; Poulsen, Asmus; Brandrup, Flemming

2003-01-01

The optimal dosage and duration of penicillin treatment for the various stages of syphilis are not known. We present data on 20 patients with syphilis (primary, secondary or latent) treated with high-dose, short-time penicillin infusion therapy. Patients were given 10 MIU of penicillin G intraven......The optimal dosage and duration of penicillin treatment for the various stages of syphilis are not known. We present data on 20 patients with syphilis (primary, secondary or latent) treated with high-dose, short-time penicillin infusion therapy. Patients were given 10 MIU of penicillin G...

PLEIOTROPIC EFFECT OF Rht3 DWARFING GENE ON SOME TRAITS OF WHEAT (Tr. aestivum L. em Thell

Directory of Open Access Journals (Sweden)

M. Jošt

2001-06-01

Full Text Available True-isogenic lines, differing only in the semi-dominant Rht3 dwarfing gene, were developed from the cross 'Tom Thumb x Bankuty 1201' during 17 years of continuous selection on heterozygous semi-dwarf plant. The effect of double (Rht3 Rht3 = full-dwarf, single (Rht3 rht3 =semi-dwarf, or no dwarfing gene (rht3 rht3 = tall dosage on some plant, seed, and flour quality traits were observed in the isogenic lines during two years field experiment, planted by 'honey-comb design' at Kri`evci, Croatia. Significant main effect of Rht3 gene was in shortening of plant height by 54% and 28% in double and single gene dosage respectively. Full-dwarf genotype (Rht3 Rht3 had by 12% more heads/plant, but the other yield components as number of grains/head, and grain weight/head were lower by 25 and 28% respectively, resulting in significantly lower grain yield/plant (-27%. However, this also could be a secondary side effect of prolonged vegetation influenced by doubled Rht3 gene. There was no significant effect on flour protein content. Double gene effect was strong and significant for maximum dough viscosity measured by amylograph in BU (101%. In our environment full dwarf (Rht3 Rht3 has no agronomic value, but single gene dosage could be of commercial interest in hybrid wheat breeding.

Administered activity of Tc-99m MDP for bone scintigraphy, standard or individual dosage?

International Nuclear Information System (INIS)

Vestergren, E.; Gretarsdottir, J.; Jacobsson, L.

2002-01-01

Background and Aim: Adult patients are generally, irrespective of size, given the same amount of activity for a certain type of nuclear medicine examination, a standard dosage. Identical image quality is essential when comparing different patient studies. The aim of this study is to evaluate different dosage methods for Tc-99m-MDP bone scintigraphy and to investigate whether individual dosage will decrease the variations in image quality between different patients. Material and Methods: 100 consecutive adult patients (aged between 40 and 89 years) undergoing whole body bone scintigraphy were studied. Eight patients were excluded from the study because of abnormal high uptake in the areas of interest. The patient weight and height were registered. The activity in the syringes was measured before and after the injection of about 600 MBq Tc-99m MDP. Scanning was performed, with a dual head gamma camera (Maxxus or Millennium VG, General Electric) equipped with a high-resolution collimator, at approximately 4 hours (mean 3.8 h) post-injection. Regions of interest (ROI) were drawn over the lumbar spine (posterior view), the right femur (anterior view) and also soft tissue background regions for each area. The total counts, maximum counts/pixel and number of pixels in the ROIs were registered. The maximum number of counts/pixel (background-subtracted), SPINEmax and FEMURmax were chosen as the image quality parameters. For each patient, SPINEmax and FEMURmax where recalculated to the number that would have been obtained with standard dosage (exactly 600 MBq), and dosage proportional to body weight, body surface area and body height. All values were corrected to a scanning time 3.8 h after injection. Results: Both with a standard activity dosage and a dosage proportional to body height, SPINEmax decreases with increasing body weight. Dosage proportional to body weight gives increasing values of SPINEmax with increasing body weight. Dosage proportional to body surface area

Dependence of surface smoothing, sputtering and etching phenomena on cluster ion dosage

CERN Document Server

Song, J H; Choi, W K

2002-01-01

The dependence of surface smoothing and sputtering phenomena of Si (1 0 0) solid surfaces irradiated by CO sub 2 cluster ions on cluster-ion dosage was investigated using an atomic force microscope. The flux and total ion dosage of impinging cluster ions at the acceleration voltage of 50 kV were fixed at 10 sup 9 ions/cm sup 2 s and were scanned from 5x10 sup 1 sup 0 to 5x10 sup 1 sup 3 ions/cm sup 2 , respectively. The density of hillocks induced by cluster ion impact was gradually increased with the dosage up to 5x10 sup 1 sup 1 ions/cm sup 2 , which caused that the irradiated surface became rough from 0.4 to 1.24 nm in root-mean-square roughness (sigma sub r sub m sub s). At the boundary of the ion dosage of 10 sup 1 sup 2 ions/cm sup 2 , the density of the induced hillocks was decreased and sigma sub r sub m sub s was about 1.21 nm, not being deteriorated further. At the dosage of 5x10 sup 1 sup 3 ions/cm sup 2 , the induced hillocks completely disappeared and the surface became very flat as much as sigma...

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

DEFF Research Database (Denmark)

Raijada, Dharaben Kaushikkumar; Genina, Natalja; Fors, Daniela

2013-01-01

The purpose of this study was to formulate printable dosage forms for a poorly soluble drug (piroxicam; PRX) and to gain understanding of critical parameters to be considered during development of such dosage forms. Liquid formulations of PRX were printed on edible paper using piezoelectric inkjet...

Maths anxiety and medication dosage calculation errors: A scoping review.

Science.gov (United States)

Williams, Brett; Davis, Samantha

2016-09-01

A student's accuracy on drug calculation tests may be influenced by maths anxiety, which can impede one's ability to understand and complete mathematic problems. It is important for healthcare students to overcome this barrier when calculating drug dosages in order to avoid administering the incorrect dose to a patient when in the clinical setting. The aim of this study was to examine the effects of maths anxiety on healthcare students' ability to accurately calculate drug dosages by performing a scoping review of the existing literature. This review utilised a six-stage methodology using the following databases; CINAHL, Embase, Medline, Scopus, PsycINFO, Google Scholar, Trip database (http://www.tripdatabase.com/) and Grey Literature report (http://www.greylit.org/). After an initial title/abstract review of relevant papers, and then full text review of the remaining papers, six articles were selected for inclusion in this study. Of the six articles included, there were three experimental studies, two quantitative studies and one mixed method study. All studies addressed nursing students and the presence of maths anxiety. No relevant studies from other disciplines were identified in the existing literature. Three studies took place in the U.S, the remainder in Canada, Australia and United Kingdom. Upon analysis of these studies, four factors including maths anxiety were identified as having an influence on a student's drug dosage calculation abilities. Ultimately, the results from this review suggest more research is required in nursing and other relevant healthcare disciplines regarding the effects of maths anxiety on drug dosage calculations. This additional knowledge will be important to further inform development of strategies to decrease the potentially serious effects of errors in drug dosage calculation to patient safety. Copyright © 2016 Elsevier Ltd. All rights reserved.

Tissue- and stage-dependent dosage compensation on the Neo-X chromosome in drosophila pseudoobscura

KAUST Repository

Nozawa, Masafumi

2013-12-03

Sex chromosome dosage compensation (DC) is widely accepted in various organisms. This concept is mostly supported by comparisons of gene expression between chromosomes and between sexes. However, genes on the X chromosome and autosomes are mostly not homologous, and the average gene expression level on these chromosomes may not be the same even under DC, which complicates comparisons between chromosomes. Many genes with sex-biased expression also make comparisons between sexes difficult. To overcome these issues, we investigated DC by comparing the expression of neo-X-linked genes in Drosophila pseudoobscura with those of their autosomal orthologs in other Drosophila species. The ratio of the former to the latter in males would be 1 under DC, whereas it becomes 0.5 without DC. We found that the ratio was ∼0.85 for adult whole bodies, indicating that the DC is incomplete on the neo-X chromosome in adults as a whole. The ratio (∼0.90) was also significantly less than 1 for adult bodies without gonads, whereas it was ∼1.0 for adult heads. These results indicate that DC varies among tissues. Our sliding-window analysis of the ratio also revealed that the upregulation of neo-X-linked genes in males occurred chromosome wide in all tissues analyzed, indicating global upregulation mechanisms. However, we found that gene functions also affected the levels of DC. Furthermore, most of the genes recently moved to the X were already under DC at the larval stage but not at the adult stage. These results suggest that DC in Drosophila species operates in a tissue/stage-dependent manner. © 2013 The Author 2013. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved.

Material Considerations for Fused-Filament Fabrication of Solid Dosage Forms

Directory of Open Access Journals (Sweden)

Evert Fuenmayor

2018-04-01

Full Text Available Material choice is a fundamental consideration when it comes to designing a solid dosage form. The matrix material will ultimately determine the rate of drug release since the physical properties (solubility, viscosity, and more of the material control both fluid ingress and disintegration of the dosage form. The bulk properties (powder flow, concentration, and more of the material should also be considered since these properties will influence the ability of the material to be successfully manufactured. Furthermore, there is a limited number of approved materials for the production of solid dosage forms. The present study details the complications that can arise when adopting pharmaceutical grade polymers for fused-filament fabrication in the production of oral tablets. The paper also presents ways to overcome each issue. Fused-filament fabrication is a hot-melt extrusion-based 3D printing process. The paper describes the problems encountered in fused-filament fabrication with Kollidon® VA64, which is a material that has previously been utilized in direct compression and hot-melt extrusion processes. Formulation and melt-blending strategies were employed to increase the printability of the material. The paper defines for the first time the essential parameter profile required for successful 3D printing and lists several pre-screening tools that should be employed to guide future material formulation for the fused-filament fabrication of solid dosage forms.

Inactivation of antibiotic resistance genes in municipal wastewater effluent by chlorination and sequential UV/chlorination disinfection

Energy Technology Data Exchange (ETDEWEB)

Zhang, Yingying; Zhuang, Yao; Geng, Jinju, E-mail: jjgeng@nju.edu.cn; Ren, Hongqiang, E-mail: hqren@nju.edu.cn; Zhang, Yan; Ding, Lili; Xu, Ke

2015-04-15

This study investigated disinfection methods including chlorination, ultraviolet (UV) irradiation and sequential UV/chlorination treatment on the inactivation of antibiotic resistance genes (ARGs). ARGs including sul1, tetX, tetG, intI1, and 16S rRNA genes in municipal wastewater treatment plant (MWTP) effluent were examined. The results indicated a positive correlation between the removal of ARGs and chlorine dosage (p = 0.007–0.014, n = 6),as well as contact time (p = 0.0001, n = 10). Greater free chlorine (FC) dosage leads to higher removal for all the genes and the maximum removal (1.30–1.49 logs) could be achieved at FC dosage of 30 mg L{sup −1}. The transformation kinetic data for ARGs removal (log C{sub 0} / C) followed the second-order reaction kinetic model with FC dosage (R{sup 2} = 0.6829–0.9999) and contact time (R{sup 2} = 0.7353–8634), respectively. Higher ammonia nitrogen (NH{sub 3}–N) concentration was found to lead to lower removal of ARGs at the same chlorine dosage. When the applied Cl{sub 2}:NH{sub 3}–N ratio was over 7.6:1, a significant reduction of ARGs (1.20–1.49 logs) was achieved. By using single UV irradiation, the log removal values of tetX and 16Ss rRNA genes were 0.58 and 0.60, respectively, while other genes were 0.36–0.40 at a fluence of 249.5 mJ cm{sup −2}, which was observed to be less effective than chlorination. With sequential UV/chlorination treatment, 0.006 to 0.31 log synergy values of target genes were observed under different operation parameters. - Highlights: • Chlorine is more effective than UV irradiation in removing ARGs from MWTP effluent. • The chlorination reaction followed the second-order reaction kinetic model. • Higher NH{sub 3}–N contents result in lower ARGs removal in the chlorination process. • FC is more effective than CC on the inactivation of ARGs. • UV irradiation followed by chlorination shows high efficiency in removing ARGs.

DR-Integrator: a new analytic tool for integrating DNA copy number and gene expression data.

Science.gov (United States)

Salari, Keyan; Tibshirani, Robert; Pollack, Jonathan R

2010-02-01

DNA copy number alterations (CNA) frequently underlie gene expression changes by increasing or decreasing gene dosage. However, only a subset of genes with altered dosage exhibit concordant changes in gene expression. This subset is likely to be enriched for oncogenes and tumor suppressor genes, and can be identified by integrating these two layers of genome-scale data. We introduce DNA/RNA-Integrator (DR-Integrator), a statistical software tool to perform integrative analyses on paired DNA copy number and gene expression data. DR-Integrator identifies genes with significant correlations between DNA copy number and gene expression, and implements a supervised analysis that captures genes with significant alterations in both DNA copy number and gene expression between two sample classes. DR-Integrator is freely available for non-commercial use from the Pollack Lab at http://pollacklab.stanford.edu/ and can be downloaded as a plug-in application to Microsoft Excel and as a package for the R statistical computing environment. The R package is available under the name 'DRI' at http://cran.r-project.org/. An example analysis using DR-Integrator is included as supplemental material. Supplementary data are available at Bioinformatics online.

Low-dosage helical CT applications for chest medical checkup and lung cancer screening

International Nuclear Information System (INIS)

Wang Ping; Cui Fa; Liang Huanqing; Zheng Minfei

2005-01-01

Objective: A discussion on low-dosage helical CT applications on chest medical checkup and lung cancer screening. Methods: On the 100 chest medical check up with three different of protocols, including standard-dosage (the tube current was 230 mAs) were compared with low-dose (tube current was 50 mAs or 30 mAs). Results: Low-dosage helical CT scan provides excellent images. In 100 chest medical checkup, 39 nodules or masses were revealed, enlarged lymph node was noted in 1 case; emphysema or bullae was demonstrated in 3 segments; thickening of bronchial wall was shown in 2 cases; and localized pleural thickening was found in 1 case. Conclusion: In chest checkup or lung cancer screening low-dosage helical CT (tube current 30 mAs) will not only guarantee image quality but also reduce the radiation dose during the examination. (authors)

QR encoded smart oral dosage forms by inkjet printing.

Science.gov (United States)

Edinger, Magnus; Bar-Shalom, Daniel; Sandler, Niklas; Rantanen, Jukka; Genina, Natalja

2018-01-30

The use of inkjet printing (IJP) technology enables the flexible manufacturing of personalized medicine with the doses tailored for each patient. In this study we demonstrate, for the first time, the applicability of IJP in the production of edible dosage forms in the pattern of a quick response (QR) code. This printed pattern contains the drug itself and encoded information relevant to the patient and/or healthcare professionals. IJP of the active pharmaceutical ingredient (API)-containing ink in the pattern of QR code was performed onto a newly developed porous and flexible, but mechanically stable substrate with a good absorption capacity. The printing did not affect the mechanical properties of the substrate. The actual drug content of the printed dosage forms was in accordance with the encoded drug content. The QR encoded dosage forms had a good print definition without significant edge bleeding. They were readable by a smartphone even after storage in harsh conditions. This approach of efficient data incorporation and data storage combined with the use of smart devices can lead to safer and more patient-friendly drug products in the future. Copyright © 2017 Elsevier B.V. All rights reserved.

Transgenic mice with increased Cu/Zn-superoxide dismutase activity: animal model of dosage effects in Down syndrome

International Nuclear Information System (INIS)

Epstein, C.J.; Avraham, K.B.; Lovett, M.; Smith, S.; Elroy-Stein, O.; Rotman, G.; Bry, C.; Groner, Y.

1987-01-01

Down syndrome, the phenotypic expression of human trisomy 21, is presumed to result from a 1.5-fold increase in the expression of the genes on human chromosome 21. As an approach to the development of an animal model for Down syndrome, several strains of transgenic mice that carry the human Cu/Zn-superoxide dismutase gene have been prepared. The animals express the transgene in a manner similar to that of humans, with 0.9- and 0.7-kilobase transcripts in a 1:4 ratio, and synthesize the human enzyme in an active form capable of forming human-mouse enzyme heterodimers. Cu/Zn-superoxide dismutase activity is increased from 1.6- to 6.0-fold in the brains of four transgenic strains and to an equal or lesser extent in several other tissues. These animals provide a unique system for studying the consequences of increased dosage of the Cu/Zn-superoxide dismutase gene in Down syndrome and the role of this enzyme in a variety of other pathological processes

Dosage-based parameters for characterization of puff dispersion results.

Science.gov (United States)

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. Copyright © 2014 Elsevier B.V. All rights reserved.

Spectrophotometric Determination of Trimipramine in Tablet Dosage ...

African Journals Online (AJOL)

Purpose: To develop and validate simple, rapid and sensitive spectrophotometric procedures for determination of trimipramine in tablet dosage form. Methods: The methods were based on the interaction of trimipramine as n-electron donor with the ο-acceptor, iodine and various π-acceptors, namely: chloranil (CH), ...

The Endosymbiotic Bacterium Wolbachia Selectively Kills Male Hosts by Targeting the Masculinizing Gene.

Directory of Open Access Journals (Sweden)

Takahiro Fukui

2015-07-01

Full Text Available Pathogens are known to manipulate the reproduction and development of their hosts for their own benefit. Wolbachia is an endosymbiotic bacterium that infects a wide range of insect species. Wolbachia is known as an example of a parasite that manipulates the sex of its host's progeny. Infection of Ostrinia moths by Wolbachia causes the production of all-female progeny, however, the mechanism of how Wolbachia accomplishes this male-specific killing is unknown. Here we show for the first time that Wolbachia targets the host masculinizing gene of Ostrinia to accomplish male-killing. We found that Wolbachia-infected O. furnacalis embryos do not express the male-specific splice variant of doublesex, a gene which acts at the downstream end of the sex differentiation cascade, throughout embryonic development. Transcriptome analysis revealed that Wolbachia infection markedly reduces the mRNA level of Masc, a gene that encodes a protein required for both masculinization and dosage compensation in the silkworm Bombyx mori. Detailed bioinformatic analysis also elucidated that dosage compensation of Z-linked genes fails in Wolbachia-infected O. furnacalis embryos, a phenomenon that is extremely similar to that observed in Masc mRNA-depleted male embryos of B. mori. Finally, injection of in vitro transcribed Masc cRNA into Wolbachia-infected embryos rescued male progeny. Our results show that Wolbachia-induced male-killing is caused by a failure of dosage compensation via repression of the host masculinizing gene. Our study also shows a novel strategy by which a pathogen hijacks the host sex determination cascade.

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

Science.gov (United States)

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

2010-09-15

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

Dosage-sensitive function of retinoblastoma related and convergent epigenetic control are required during the Arabidopsis life cycle.

Directory of Open Access Journals (Sweden)

Amal J Johnston

2010-06-01

Full Text Available The plant life cycle alternates between two distinct multi-cellular generations, the reduced gametophytes and the dominant sporophyte. Little is known about how generation-specific cell fate, differentiation, and development are controlled by the core regulators of the cell cycle. In Arabidopsis, RETINOBLASTOMA RELATED (RBR, an evolutionarily ancient cell cycle regulator, controls cell proliferation, differentiation, and regulation of a subset of Polycomb Repressive Complex 2 (PRC2 genes and METHYLTRANSFERASE 1 (MET1 in the male and female gametophytes, as well as cell fate establishment in the male gametophyte. Here we demonstrate that RBR is also essential for cell fate determination in the female gametophyte, as revealed by loss of cell-specific marker expression in all the gametophytic cells that lack RBR. Maintenance of genome integrity also requires RBR, because diploid plants heterozygous for rbr (rbr/RBR produce an abnormal portion of triploid offspring, likely due to gametic genome duplication. While the sporophyte of the diploid mutant plants phenocopied wild type due to the haplosufficiency of RBR, genetic analysis of tetraploid plants triplex for rbr (rbr/rbr/rbr/RBR revealed that RBR has a dosage-dependent pleiotropic effect on sporophytic development, trichome differentiation, and regulation of PRC2 subunit genes CURLY LEAF (CLF and VERNALIZATION 2 (VRN2, and MET1 in leaves. There were, however, no obvious cell cycle and cell proliferation defects in these plant tissues, suggesting that a single functional RBR copy in tetraploids is capable of maintaining normal cell division but is not sufficient for distinct differentiation and developmental processes. Conversely, in leaves of mutants in sporophytic PRC2 subunits, trichome differentiation was also affected and expression of RBR and MET1 was reduced, providing evidence for a RBR-PRC2-MET1 regulatory feedback loop involved in sporophyte development. Together, dosage-sensitive RBR

Biowaiver monograph for immediate-release solid oral dosage forms: fluconazole.

Science.gov (United States)

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. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

Accelerated in-vitro release testing methods for extended-release parenteral dosage forms.

Science.gov (United States)

Shen, Jie; Burgess, Diane J

2012-07-01

This review highlights current methods and strategies for accelerated in-vitro drug release testing of extended-release parenteral dosage forms such as polymeric microparticulate systems, lipid microparticulate systems, in-situ depot-forming systems and implants. Extended-release parenteral dosage forms are typically designed to maintain the effective drug concentration over periods of weeks, months or even years. Consequently, 'real-time' in-vitro release tests for these dosage forms are often run over a long time period. Accelerated in-vitro release methods can provide rapid evaluation and therefore are desirable for quality control purposes. To this end, different accelerated in-vitro release methods using United States Pharmacopeia (USP) apparatus have been developed. Different mechanisms of accelerating drug release from extended-release parenteral dosage forms, along with the accelerated in-vitro release testing methods currently employed are discussed. Accelerated in-vitro release testing methods with good discriminatory ability are critical for quality control of extended-release parenteral products. Methods that can be used in the development of in-vitro-in-vivo correlation (IVIVC) are desirable; however, for complex parenteral products this may not always be achievable. © 2012 The Authors. JPP © 2012 Royal Pharmaceutical Society.

Accelerated in vitro release testing methods for extended release parenteral dosage forms

Science.gov (United States)

Shen, Jie; Burgess, Diane J.

2012-01-01

Objectives This review highlights current methods and strategies for accelerated in vitro drug release testing of extended release parenteral dosage forms such as polymeric microparticulate systems, lipid microparticulate systems, in situ depot-forming systems, and implants. Key findings Extended release parenteral dosage forms are typically designed to maintain the effective drug concentration over periods of weeks, months or even years. Consequently, “real-time” in vitro release tests for these dosage forms are often run over a long time period. Accelerated in vitro release methods can provide rapid evaluation and therefore are desirable for quality control purposes. To this end, different accelerated in vitro release methods using United States Pharmacopoeia (USP) apparatus have been developed. Different mechanisms of accelerating drug release from extended release parenteral dosage forms, along with the accelerated in vitro release testing methods currently employed are discussed. Conclusions Accelerated in vitro release testing methods with good discriminatory ability are critical for quality control of extended release parenteral products. Methods that can be used in the development of in vitro-in vivo correlation (IVIVC) are desirable, however for complex parenteral products this may not always be achievable. PMID:22686344

Nature of gene action for fruit quality characters of tomato (Solanum ...

African Journals Online (AJOL)

Prof. P. Hazra

2013-05-15

May 15, 2013 ... additive x additive type non-allelic interaction with negative sign for the characters, which will hinder ..... artificial gene dosage series in tomato to study the mechanisms by ... physical properties affected by food processing.

Biowaiver monograph for immediate-release solid oral dosage forms: bisoprolol fumarate.

Science.gov (United States)

Charoo, Naseem A; Shamsher, Areeg A A; Lian, Lai Y; Abrahamsson, Bertil; Cristofoletti, Rodrigo; Groot, D W; Kopp, Sabine; Langguth, Peter; Polli, James; Shah, Vinod P; Dressman, Jennifer

2014-02-01

Literature data relevant to the decision to allow a waiver of in vivo bioequivalence (BE) testing for the approval of immediate-release (IR) solid oral dosage forms containing bisoprolol as the sole active pharmaceutical ingredient (API) are reviewed. Bisoprolol is classified as a Class I API according to the current Biopharmaceutics Classification System (BCS). In addition to the BCS class, its therapeutic index, pharmacokinetic properties, data related to the possibility of excipient interactions, and reported BE/bioavailability problems are taken into consideration. Qualitative compositions of IR tablet dosage forms of bisoprolol with a marketing authorization (MA) in ICH (International Conference on Harmonisation) countries are tabulated. It was inferred that these tablets had been demonstrated to be bioequivalent to the innovator product. No reports of failure to meet BE standards have been made in the open literature. On the basis of all these pieces of evidence, a biowaiver can currently be recommended for bisoprolol fumarate IR dosage forms if (1) the test product contains only excipients that are well known, and used in normal amounts, for example, those tabulated for products with MA in ICH countries and (2) both the test and comparator dosage form are very rapidly dissolving, or, rapidly dissolving with similarity of the dissolution profiles demonstrated at pH 1.2, 4.5, and 6.8. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association.

Endotoxin dosage in sepsis

Directory of Open Access Journals (Sweden)

Vincenzo Rondinelli

2012-03-01

Full Text Available Introduction. Endotoxin, a component of the cell wall of Gram-negative bacteria is a major contributor to the pathogenesis of septic shock and multiple organ failure (MOF. Its entry into the bloodstream stimulates monocytes/macrophages which once activated produce and release cytokines, nitric oxide and other mediators that induce systemic inflammation, endothelial damage, organ dysfunction, hypotension (shock and MOF.The aim of this study is to evaluate the usefulness of a quantitative test for the dosage of endotoxin to determine the risk of severe Gram-negative sepsis. Materials and methods. In the period January 2009 - June 2011 we performed 897 tests for 765 patients, mostly coming from the emergency room and intensive care, of which 328 (43% women (mean age 53 and 437 (57% male (mean age 49. Fifty-nine patients, no statistically significant difference in sex, were monitored by an average of two determinations of EA.All patients had procalcitonin values significantly altered.The kit used was EAA (Endotoxin Activity Assay Estor Company, Milan, which has three ranges of endotoxin activity (EA: low risk of sepsis if <0.40 units, medium if between 0.40 and 0.59; high if 0.60. Results. 78 out of 765 patients (10% had a low risk, 447 (58% a medium risk and 240 (32% a high risk.The dosage of EA, combined with that of procalcitonin, has allowed a more targeted antibiotic therapy. Six patients in serious clinical conditions were treated by direct hemoperfusion with Toraymyxin, a device comprising a housing containing a fiber polypropylene and polystyrene with surface-bound polymyxin B, an antibiotic that removes bacterial endotoxins from the blood. Conclusions.The test is useful in risk stratification as well as Gram negative sepsis, to set and monitor targeted therapies, also based on the neutralization of endotoxin.

Intrathecal baclofen in multiple sclerosis and spinal cord injury: complications and long-term dosage evolution.

Science.gov (United States)

Draulans, Nathalie; Vermeersch, Kristof; Degraeuwe, Bart; Meurrens, Tom; Peers, Koen; Nuttin, Bart; Kiekens, Carlotte

2013-12-01

To investigate the long-term dosage evolution and complication rate of intrathecal baclofen use in multiple sclerosis and spinal cord injury patients, based on a large population with a long follow-up. Retrospective data analysis. Academic hospital. Patients with multiple sclerosis (n = 81) or spinal cord injury (n = 49) having an intrathecal baclofen pump implanted at the University Hospitals Leuven between 1988 and 2009. Medical records review of included patients in August 2010. Complications linked to intrathecal baclofen therapy. Daily baclofen dosage after 3 and 6 months, and yearly thereafter. Data on dosage evolution were analysed using a mixed-effect linear model. In 130 patients with a mean follow-up of 63 months, comprising 797 pump years, 104 complications were recorded. This corresponds to a complication rate of 0.011 per month, equally divided among both groups. Seventy-eight of these complications were catheter related. The mean dosage of baclofen stabilizes two years after implantation at 323 µg/day in the multiple sclerosis population. In spinal cord injury patients the daily dose only stabilizes after five years at a significantly higher dosage (504 µg/day). No significant increase in dosage is seen in the long term. In multiple sclerosis and spinal cord injury patients, intrathecal baclofen therapy has a complication rate of 1% per month. Complications are mainly due to catheter-related problems (74%). The intrathecal baclofen dosage stabilizes in the long term, indicating that long-term tolerance, defined as progressive diminution of the susceptibility to the effects of a drug, is not present.

Spectrophotometric Determination of Cilostazol in Tablet Dosage Form

African Journals Online (AJOL)

Purpose: To develop simple, rapid and selective spectrophotometric methods for the determination of cilostazol in tablet dosage form. Methods: Cilostazol was dissolved in 50 % methanol and its absorbance was scanned by ultraviolet (UV) spectrophotometry. Both linear regression equation and standard absorptivity were ...

Fourteen days oral administration of therapeutic dosage of some ...

African Journals Online (AJOL)

Fourteen days oral administration of therapeutic dosage of some antibiotics reduced serum testosterone in male rats. FO Awobajo, Y Raji, II Olatunji-Bello, FT Kunle-Alabi, AO Adesanya, TO Awobajo ...

Optimizing the dosage of stabilizing chemical

OpenAIRE

Harjula, Tomi

2013-01-01

A chemical company provides chemical treatment at customer mill in paper industry. This thesis work was done to determine the optimum dosage of stabilizing chemical. The theoretical framework explains the basics of paper brightness and bleaching and how these topics are connected to each other. The knowledge gained is very valuable and can possibly be used in the future in other similar applications as well. This thesis work contains confidential back ground information. Key ...

Methotrexate Dosage Reduction Upon Adalimumab Initiation: Clinical and Ultrasonographic Outcomes from the Randomized Noninferiority MUSICA Trial.

Science.gov (United States)

Kaeley, Gurjit S; Evangelisto, Amy M; Nishio, Midori J; Goss, Sandra L; Liu, Shufang; Kalabic, Jasmina; Kupper, Hartmut

2016-08-01

To examine the clinical and ultrasonographic (US) outcomes of reducing methotrexate (MTX) dosage upon initiating adalimumab (ADA) in MTX-inadequate responders with moderately to severely active rheumatoid arthritis (RA). MUSICA (NCT01185288) was a double-blind, randomized, parallel-arm study of 309 patients with RA receiving MTX ≥ 15 mg/week for ≥ 12 weeks before screening. Patients were randomized to high dosage (20 mg/week) or low dosage (7.5 mg/week) MTX; all patients received 40 mg open-label ADA every other week for 24 weeks. The primary endpoint was Week 24 mean 28-joint Disease Activity Score based on C-reactive protein (DAS28-CRP) to test for noninferiority of low-dosage MTX using a 15% margin. US images were scored using a 10-joint semiquantitative system incorporating OMERACT definitions for pathology, assessing synovial hypertrophy, vascularity, and bony erosions. Rapid improvement in clinical indices was observed in both groups after addition of ADA. The difference in mean DAS28-CRP (0.37, 95% CI 0.07-0.66) comparing low-dosage (4.12, 95% CI 3.88-4.34) versus high-dosage MTX (3.75, 95% CI 3.52-3.97) was statistically significant and non-inferiority was not met. Statistically significant differences were not detected for most clinical, functional, and US outcomes. Pharmacokinetic and safety profiles were similar. In MUSICA, Week 24 mean DAS28-CRP, the primary endpoint, did not meet non-inferiority for the low-dosage MTX group. Although the differences between the 2 MTX dosage groups were small, our study findings did not support routine MTX reduction in MTX inadequate responders initiating ADA.

Measurement of the lowest dosage of phenobarbital that can produce drug discrimination in rats

Science.gov (United States)

Overton, Donald A.; Stanwood, Gregg D.; Patel, Bhavesh N.; Pragada, Sreenivasa R.; Gordon, M. Kathleen

2009-01-01

Rationale Accurate measurement of the threshold dosage of phenobarbital that can produce drug discrimination (DD) may improve our understanding of the mechanisms and properties of such discrimination. Objectives Compare three methods for determining the threshold dosage for phenobarbital (D) versus no drug (N) DD. Methods Rats learned a D versus N DD in 2-lever operant training chambers. A titration scheme was employed to increase or decrease dosage at the end of each 18-day block of sessions depending on whether the rat had achieved criterion accuracy during the sessions just completed. Three criterion rules were employed, all based on average percent drug lever responses during initial links of the last 6 D and 6 N sessions of a block. The criteria were: D%>66 and N%50 and N%33. Two squads of rats were trained, one immediately after the other. Results All rats discriminated drug versus no drug. In most rats, dosage decreased to low levels and then oscillated near the minimum level required to maintain criterion performance. The lowest discriminated dosage significantly differed under the three criterion rules. The squad that was trained 2nd may have benefited by partially duplicating the lever choices of the previous squad. Conclusions The lowest discriminated dosage is influenced by the criterion of discriminative control that is employed, and is higher than the absolute threshold at which discrimination entirely disappears. Threshold estimations closer to absolute threshold can be obtained when criteria are employed that are permissive, and that allow rats to maintain lever preferences. PMID:19082992

[Post-marketing re-evaluation about usage and dosage of Chinese medicine based on human population pharmacokinetics].

Science.gov (United States)

Jiang, Junjie; Xie, Yanming

2011-10-01

The usage and dosage of Chinese patent medicine are determined by rigorous evaluation which include four clinical trail stages: I, II, III. But the usage and dosage of Chinese patent medicine are lacked re-evaluation after marketing. And this lead to unchanging or fixed of the usage and dosage of Chinese patent medicine instead of different quantity based on different situations in individual patients. The situation of Chinese patent medicine used in clinical application is far away from the idea of the "Treatment based on syndrome differentiation" in traditional Chinese medicine and personalized therapy. Human population pharmacokinetics provides data support to the personalized therapy in clinical application, and achieved the postmarking reevaluating of the usage and dosage of Chinese patent medicine. This paper briefly introduced the present situation, significance and the application of human population pharmacokinetics about re-evaluation of the usage and dosage of Chinese patent medicine after marketing.

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

Science.gov (United States)

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. Copyright © 2016. Published by Elsevier B.V.

Boxing and mixed martial arts: preliminary traumatic neuromechanical injury risk analyses from laboratory impact dosage data.

Science.gov (United States)

Bartsch, Adam J; Benzel, Edward C; Miele, Vincent J; Morr, Douglas R; Prakash, Vikas

2012-05-01

In spite of ample literature pointing to rotational and combined impact dosage being key contributors to head and neck injury, boxing and mixed martial arts (MMA) padding is still designed to primarily reduce cranium linear acceleration. The objects of this study were to quantify preliminary linear and rotational head impact dosage for selected boxing and MMA padding in response to hook punches; compute theoretical skull, brain, and neck injury risk metrics; and statistically compare the protective effect of various glove and head padding conditions. An instrumented Hybrid III 50th percentile anthropomorphic test device (ATD) was struck in 54 pendulum impacts replicating hook punches at low (27-29 J) and high (54-58 J) energy. Five padding combinations were examined: unpadded (control), MMA glove-unpadded head, boxing glove-unpadded head, unpadded pendulum-boxing headgear, and boxing glove-boxing headgear. A total of 17 injury risk parameters were measured or calculated. All padding conditions reduced linear impact dosage. Other parameters significantly decreased, significantly increased, or were unaffected depending on padding condition. Of real-world conditions (MMA glove-bare head, boxing glove-bare head, and boxing glove-headgear), the boxing glove-headgear condition showed the most meaningful reduction in most of the parameters. In equivalent impacts, the MMA glove-bare head condition induced higher rotational dosage than the boxing glove-bare head condition. Finite element analysis indicated a risk of brain strain injury in spite of significant reduction of linear impact dosage. In the replicated hook punch impacts, all padding conditions reduced linear but not rotational impact dosage. Head and neck dosage theoretically accumulates fastest in MMA and boxing bouts without use of protective headgear. The boxing glove-headgear condition provided the best overall reduction in impact dosage. More work is needed to develop improved protective padding to minimize

Volcanic ash dosage calculator: A proof-of-concept tool to support aviation stakeholders during ash events

Science.gov (United States)

Dacre, H.; Prata, A.; Shine, K. P.; Irvine, E.

2017-12-01

The volcanic ash clouds produced by Icelandic volcano Eyjafjallajökull in April/May 2010 resulted in `no fly zones' which paralysed European aircraft activity and cost the airline industry an estimated £1.1 billion. In response to the crisis, the Civil Aviation Authority (CAA), in collaboration with Rolls Royce, produced the `safe-to-fly' chart. As ash concentrations are the primary output of dispersion model forecasts, the chart was designed to illustrate how engine damage progresses as a function of ash concentration. Concentration thresholds were subsequently derived based on previous ash encounters. Research scientists and aircraft manufactures have since recognised the importance of volcanic ash dosages; the accumulated concentration over time. Dosages are an improvement to concentrations as they can be used to identify pernicious situations where ash concentrations are acceptably low but the exposure time is long enough to cause damage to aircraft engines. Here we present a proof-of-concept volcanic ash dosage calculator; an innovative, web-based research tool, developed in close collaboration with operators and regulators, which utilises interactive data visualisation to communicate the uncertainty inherent in dispersion model simulations and subsequent dosage calculations. To calculate dosages, we use NAME (Numerical Atmospheric-dispersion Modelling Environment) to simulate several Icelandic eruption scenarios, which result in tephra dispersal across the North Atlantic, UK and Europe. Ash encounters are simulated based on flight-optimal routes derived from aircraft routing software. Key outputs of the calculator include: the along-flight dosage, exposure time and peak concentration. The design of the tool allows users to explore the key areas of uncertainty in the dosage calculation and to visualise how this changes as the planned flight path is varied. We expect that this research will result in better informed decisions from key stakeholders during

Adaptive response to chronic mild ethanol stress involves ROS, sirtuins and changes in chromosome dosage in wine yeasts.

Science.gov (United States)

Adamczyk, Jagoda; Deregowska, Anna; Skoneczny, Marek; Skoneczna, Adrianna; Kwiatkowska, Aleksandra; Potocki, Leszek; Rawska, Ewa; Pabian, Sylwia; Kaplan, Jakub; Lewinska, Anna; Wnuk, Maciej

2016-05-24

Industrial yeast strains of economic importance used in winemaking and beer production are genomically diverse and subjected to harsh environmental conditions during fermentation. In the present study, we investigated wine yeast adaptation to chronic mild alcohol stress when cells were cultured for 100 generations in the presence of non-cytotoxic ethanol concentration. Ethanol-induced reactive oxygen species (ROS) and superoxide signals promoted growth rate during passages that was accompanied by increased expression of sirtuin proteins, Sir1, Sir2 and Sir3, and DNA-binding transcription regulator Rap1. Genome-wide array-CGH analysis revealed that yeast genome was shaped during passages. The gains of chromosomes I, III and VI and significant changes in the gene copy number in nine functional gene categories involved in metabolic processes and stress responses were observed. Ethanol-mediated gains of YRF1 and CUP1 genes were the most accented. Ethanol also induced nucleolus fragmentation that confirms that nucleolus is a stress sensor in yeasts. Taken together, we postulate that wine yeasts of different origin may adapt to mild alcohol stress by shifts in intracellular redox state promoting growth capacity, upregulation of key regulators of longevity, namely sirtuins and changes in the dosage of genes involved in the telomere maintenance and ion detoxification.

Digital and conventional radiology techniques: comparison of dosage and costs

International Nuclear Information System (INIS)

Arranza, L.; Albornoz, C. de

1996-01-01

To compare the radiation dosage and costs in conventional and digital technologies. The study dealt with transverse sections. The dosage applied with conventional technology was measured in 254 patients who intertwined 402 explorations of 6 anatomic regions in 4 Radiodiagnostic Services. The dosage applied with digital technology was measured in 57 patients who underwent 95 explorations of the same anatomic region in one Radiodiagnostic Service. The costs of the 6 types of conventional and digital explorations performed were calculated for two Radiodiagnostic Service. The doses administered (mGy) using convectional/digital technology were as follows: chest PA 0.2/0.1; chest LAT 0.7/0.3; breast CC 7.0/8.4; breast LAT 7.0/7.8; breast OB 7.0/10.5; cervical spine AP 9.6/9.0; cervical spine LAT 21.9/29.6; pelvis AP 7.3/7.1; plain abdominal 6.5/2.2. The costs incurred (1992 pesetas) with the convectional/digital technologies: chest AP and LAT 1,393/2,973; portable chest 2,027/3,714; mammography 2,357/3,486; phlebography 12,718/14,023; hysterosalpingography 4,876/6,701; bone scientigraphy 1,633/2,839. Compared with conventional technology, digital imaging reduces the radiation doses received by the patients, except in the case of mammography. The costs associated with the use of digital technology are greater than those incurred with conventional technology, mainly due to the costs of amortization. the use of digital technology is more justified when: 1) it is very necessary to reduce the dosage; 2) studies of chest and abdomen predominant; 3) the volume of utilization is high; 4) staff management is flexible , and 5) the cost of purchasing the equipment is lower. (Author) 10 refs

Gene amplification as a cause of inherited thyroxine-binding globulin excess in two Japanese families

Energy Technology Data Exchange (ETDEWEB)

Mori, Yuichi; Miura, Yoshitaka; Saito, Hidehiko [Toyota Memorial Hospital (Japan)] [and others

1995-12-01

T{sub 4}-binding globulin (TBG) is the major thyroid hormone transport protein in man. Inherited abnormalities in the level of serum TBG have been classified as partial deficiency, complete deficiency, and excess. Sequencing analysis of the TBG gene, located on Xq21-22, has uncovered the molecular defects causing partial and complete deficiency. However, the mechanism leading to inherited TBG excess remains unknown. In this study, two Japanese families, F-A and F-T, with inherited TBG excess were analyzed. Serum TBG levels in hemizygous males were 58 and 44 {mu}g/mL, 3- and 2-fold the normal value, respectively. The molecule had normal properties in terms of heat stability and isoelectric focussing pattern. The sequence of the coding region and the promoter activity of the TBG gene were also indistinguishable between hemizygotes and normal subjects. The gene dosage of TBG relative to that of {beta}-globin, which is located on chromosome 11, and Duchenne muscular dystropy, which is located on Xp, was evaluated by coamplification of these target genes using polymerase chain reaction and subsequent quantitation by HPLC. The TBG/{beta}-globin ratios of the affected male and female of F-A were 3.13 and 4.13 times, respectively, that in the normal males. The TBG/Duchenne muscular dystrophy ratios were 2.92 and 2.09 times the normal value, respectively. These results are compatible with three copies of TBG gene on the affected X-chromosome. Similarly, a 2-fold increase in gene dosage was demonstrated in the affected hemizygote of F-T. A 3-fold tandem amplification of the TBG gene was shown by in situ hybridization of prometaphase and interphase chromosomes from the affected male with a biotinylated genomic TBG probe, confirming the gene dosage results. Gene amplification of TBG is the cause of inherited TBG excess in these two families. 35 refs., 3 figs., 2 tabs.

Phenotypic reversion in fas mutants of Arabidopsis thaliana by reintroduction of FAS genes: variable recovery of telomeres with major spatial rearrangements and transcriptional reprogramming of 45S rDNA genes

Czech Academy of Sciences Publication Activity Database

Pavlištová, V.; Dvořáčková, Martina; Jež, M.; Mozgová, I.; Mokroš, P.; Fajkus, Jiří

2016-01-01

Roč. 88, č. 3 (2016), s. 411-424 ISSN 0960-7412 Institutional support: RVO:68081707 Keywords : chromatin assembly factor-1 * ribosomal-rna genes * dosage control Subject RIV: BO - Biophysics Impact factor: 5.901, year: 2016

Minimum effective dosages of anti-TNF in rheumatoid arthritis: a cross-sectional study.

Science.gov (United States)

de la Torre, Inmaculada; Valor, Lara; Nieto, Juan Carlos; Montoro, María; Carreño, Luis

2014-01-01

To evaluate the modified dosages of anti-TNF in controlling disease activity in rheumatoid arthritis (RA) measured by DAS28-ESR. Cross-sectional study: RA patients treated with etanercept (ETN), adalimumab (ADA) or infliximab (IFX), at standard or modified doses. dosage, concomitant disease modifying drugs (DMARDs), DAS28-ESR. 195 RA patients included (79% women, mean age 58.1 years): ETN=81, ADA=56, IFX=58. Mean disease duration and time to first biological treatment was higher in IFX group (P=.01). Patients distribution by dosage: standard: ETN (72.8%), ADA (69.6%), IFX (27.6%); escalated: IFX (69%), ADA (5.4%), ETN (0%); reduced: ETN (27.1%), ADA (25%), IFX (3.4%). Concomitant DMARDs use was lower in ETN (58.2%) than ADA (66.07%) and IFX (79.31%). Higher proportion of responders (DAS28 ≤3.2) in ADA (65.3%) and ETN (61.7%) than IFX (48.3%). RA clinical control can be preserved with modified anti-TNF dosages. Controlled prospective studies should be performed to define when therapy can be tailored and for which patients. Copyright © 2013 Elsevier España, S.L. All rights reserved.

ABCB1 genetic variability and methadone dosage requirements in opioid-dependent individuals.

Science.gov (United States)

Coller, Janet K; Barratt, Daniel T; Dahlen, Karianne; Loennechen, Morten H; Somogyi, Andrew A

2006-12-01

The most common treatment for opioid dependence is substitution therapy with another opioid such as methadone. The methadone dosage is individualized but highly variable, and program retention rates are low due in part to nonoptimal dosing resulting in withdrawal symptoms and further heroin craving and use. Methadone is a substrate for the P-glycoprotein transporter, encoded by the ABCB1 gene, which regulates central nervous system exposure. This retrospective study aimed to investigate the influence of ABCB1 genetic variability on methadone dose requirements. Genomic deoxyribonucleic acid was isolated from opioid-dependent subjects (n = 60) and non-opioid-dependent control subjects (n = 60), and polymerase chain reaction-restriction fragment length polymorphism and allele-specific polymerase chain reaction were used to determine the presence of single nucleotide polymorphisms at positions 61, 1199, 1236, 2677, and 3435. ABCB1 haplotypes were inferred with PHASE software (version 2.1). There were no significant differences in the allele or genotype frequencies of the individual single nucleotide polymorphisms or haplotypes between the 2 populations. ABCB1 genetic variability influenced daily methadone dose requirements, such that subjects carrying 2 copies of the wild-type haplotype required higher doses compared with those with 1 copy and those with no copies (98.3 +/- 10.4, 58.6 +/- 20.9, and 55.4 +/- 26.1 mg/d, respectively; P = .029). In addition, carriers of the AGCTT haplotype required significantly lower doses than noncarriers (38.0 +/- 16.8 and 61.3 +/- 24.6 mg/d, respectively; P = .04). Although ABCB1 genetic variability is not related to the development of opioid dependence, identification of variant haplotypes may, after larger prospective studies have been performed, provide clinicians with a tool for methadone dosage individualization.

Integration of gene dosage and gene expression in non-small cell lung cancer, identification of HSP90 as potential target.

Directory of Open Access Journals (Sweden)

Mariëlle I Gallegos Ruiz

Full Text Available BACKGROUND: Lung cancer causes approximately 1.2 million deaths per year worldwide, and non-small cell lung cancer (NSCLC represents 85% of all lung cancers. Understanding the molecular events in non-small cell lung cancer (NSCLC is essential to improve early diagnosis and treatment for this disease. METHODOLOGY AND PRINCIPAL FINDINGS: In an attempt to identify novel NSCLC related genes, we performed a genome-wide screening of chromosomal copy number changes affecting gene expression using microarray based comparative genomic hybridization and gene expression arrays on 32 radically resected tumor samples from stage I and II NSCLC patients. An integrative analysis tool was applied to determine whether chromosomal copy number affects gene expression. We identified a deletion on 14q32.2-33 as a common alteration in NSCLC (44%, which significantly influenced gene expression for HSP90, residing on 14q32. This deletion was correlated with better overall survival (P = 0.008, survival was also longer in patients whose tumors had low expression levels of HSP90. We extended the analysis to three independent validation sets of NSCLC patients, and confirmed low HSP90 expression to be related with longer overall survival (P = 0.003, P = 0.07 and P = 0.04. Furthermore, in vitro treatment with an HSP90 inhibitor had potent antiproliferative activity in NSCLC cell lines. CONCLUSIONS: We suggest that targeting HSP90 will have clinical impact for NSCLC patients.

Continuous intravenous infusion of ampicillin and gentamicin during parenteral nutrition to 36 newborn infants using a dosage schedule

DEFF Research Database (Denmark)

Colding, H; Møller, S; Andersen, G E

1984-01-01

Ampicillin and gentamicin were given continuously i.v. to 36 newborn infants using a dosage schedule and the results were compared with those obtained in an earlier study including 88 infants who received individually calculated dosages. With the dosage schedule the variation in the serum concent...

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

Science.gov (United States)

Kristó, Katalin; Pintye-Hódi, Klára

2013-02-01

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

3D printing of high drug loaded dosage forms using thermoplastic polyurethanes.

Science.gov (United States)

Verstraete, G; Samaro, A; Grymonpré, W; Vanhoorne, V; Van Snick, B; Boone, M N; Hellemans, T; Van Hoorebeke, L; Remon, J P; Vervaet, C

2018-01-30

It was the aim of this study to develop high drug loaded (>30%, w/w), thermoplastic polyurethane (TPU)-based dosage forms via fused deposition modelling (FDM). Model drugs with different particle size and aqueous solubility were pre-processed in combination with diverse TPU grades via hot melt extrusion (HME) into filaments with a diameter of 1.75 ± 0.05 mm. Subsequently, TPU-based filaments which featured acceptable quality attributes (i.e. consistent filament diameter, smooth surface morphology and good mechanical properties) were printed into tablets. The sustained release potential of the 3D printed dosage forms was tested in vitro. Moreover, the impact of printing parameters on the in vitro drug release was investigated. TPU-based filaments could be loaded with 60% (w/w) fine drug powder without observing severe shark skinning or inconsistent filament diameter. During 3D printing experiments, HME filaments based on hard TPU grades were successfully converted into personalized dosage forms containing a high concentration of crystalline drug (up to 60%, w/w). In vitro release kinetics were mainly affected by the matrix composition and tablet infill degree. Therefore, this study clearly demonstrated that TPU-based FDM feedstock material offers a lot of formulation freedom for the development of personalized dosage forms. Copyright © 2017 Elsevier B.V. All rights reserved.

Prevalence and trends of cellulosics in pharmaceutical dosage forms.

Science.gov (United States)

Mastropietro, David J; Omidian, Hossein

2013-02-01

Many studies have shown that cellulose derivatives (cellulosics) can provide various benefits when used in virtually all types of dosage forms. Nevertheless, the popularity of their use in approved drug products is rather unknown. This research reports the current prevalence and trends of use for 15 common cellulosics in prescription drug products. The cellulosics were powdered and microcrystalline cellulose (MCC), ethyl cellulose, hydroxypropyl cellulose (HPC), hydroxyethyl cellulose (HEC), hypromellose (HPMC), HPMC phthalate, HPMC acetate succinate, cellulose acetate (CA), CA phthalate, sodium (Na) and calcium (Ca) carboxymethylcellulose (CMC), croscarmellose sodium (XCMCNa), methyl cellulose, and low substituted HPC. The number of brand drug products utilizing each cellulosics was determined using the online drug index Rxlist. A total of 607 brand products were identified having one or more of the cellulosics as an active or inactive ingredient. An array of various dosage forms was identified and revealed HPMC and MCC to be the most utilized cellulosics in all products followed by XCMCNa and HPC. Many products contained two or more cellulosics in the formulation (42% containing two, 23% containing three, and 4% containing 4-5). The largest combination occurrence was HPMC with MCC. The use of certain cellulosics within different dosage form types was found to contain specific trends. All injectables utilized only CMCNa, and the same with all ophthalmic solutions utilizing HPMC, and otic suspensions utilizing HEC. Popularity and trends regarding cellulosics use may occur based on many factors including functionality, safety, availability, stability, and ease of manufacturing.

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

Science.gov (United States)

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. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

The effect of dosages of microbial consortia formulation and synthetic fertilizer on the growth and yield of field-grown chili

Science.gov (United States)

Istifadah, N.; Sapta, D.; Krestini, H.; Natalie, B.; Suryatmana, P.; Nurbaity, A.; Hidersah, R.

2018-03-01

Chili (Capsicum annuum, L) is one of important horticultural crop in Indonesia. Formulation of microbial consortia containing Bacillus subtilis, Pseudomonas sp., Azotobacter chroococcum and Trichoderma harzianum has been developed. This study evaluated the effects of dosage of the microbial formulation combined with NPK fertilizer on growth and yield of chili plants in the field experiment. The experiment was arranged in completely randomized design of factorial, in which the first factor was dosage of formulation (0, 2.5, 5.0, 7.5, 10 g per plant) and the second factor was NPK fertilizer dosage (0, 25, 50 and 75% of the standard dosage). The treatments were replicated three times. For application, the formulation was mixed with chicken manure 1:10 (w/v). The results showed that application of microbial formulation solely improved the chili growth. There was interaction between dosages of the microbial formulation and NPK fertilizer in improving plant height, nitrogen availability and the chili yield, while there was no interaction between those dosages in improving the root length. Combination between microbial formulation at the dosage of 5.0-7.5 g per plant combined with NPK fertilizer with the dosage 50 or 75% of the standard dosage support relatively better growth and the chili yield.

Histomorphological study of submandibulary glands of rats submitted to low dosage of X-radiation

International Nuclear Information System (INIS)

Navarro, Claudia Maria; Onofre, Mirian Aparecida; Chan, Carolina; Cordeiro, Rita de Cassis Loiola; Raveli, Dirceu Barnabe

1996-01-01

The minimal dosage of X-ray that is likely to induce cellular alterations is unknown and there are just a few reports with low dosage in odontologic literature. The authors developed a histomorphological analysis of the submandibulary glands of rat that received low dosage of X radiation. The body of the animals was covered with a lead lamin leaving the cervical area uncovered. The submandibular glands were exposed to 1,80 Gy of X-radiation in a single dose. After 24, 48, 72 hours, 7, 14 and 21 days the glands were excised, fixed and prepared for analysis in light microscopy. Mild degenerative changes and nuclear pleomorfism, mainly on the first three experimental periods were observed. (author)

21 CFR 520.1448 - Monensin oral dosage forms.

Science.gov (United States)

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... distance the spots travel from the starting line divided by the distance the solvent front travels from the...

Sprouty gene dosage influences temporal-spatial dynamics of primary enamel knot formation

Czech Academy of Sciences Publication Activity Database

Lochovská, Kateřina; Peterková, Renata; Pavlíková, Zuzana; Hovořáková, Mária

2015-01-01

Roč. 15, APR 22 (2015), s. 21 ISSN 1471-213X R&D Projects: GA ČR(CZ) GAP305/12/1766; GA ČR GB14-37368G Institutional support: RVO:68378041 Keywords : enamel knot * tooth development * mouse molar * sprouty genes * sonic hedgehog * cre-loxp system * supernumerary tooth Subject RIV: EA - Cell Biology Impact factor: 2.096, year: 2015

Estimated Effect of Epoetin Dosage on Survival among Elderly Hemodialysis Patients in the United States

OpenAIRE

Zhang, Yi; Thamer, Mae; Cotter, Dennis; Kaufman, James; Hernán, Miguel A.

2009-01-01

Background and objectives: The common finding that low achieved hemoglobin in observational studies and high target hemoglobin in randomized trials each were associated with increased mortality and high epoetin dosage has suggested the possibility that high epoetin dosage might explain the increased mortality risk.

Hyperintense acute reperfusion marker is associated with higher contrast agent dosage in acute ischaemic stroke

Energy Technology Data Exchange (ETDEWEB)

Ostwaldt, Ann-Christin; Schaefer, Tabea; Villringer, Kersten; Fiebach, Jochen B. [Charite Universitaetsmedizin Berlin, Academic Neuroradiology, Center for Stroke Research Berlin (CSB), Berlin (Germany); Rozanski, Michal; Ebinger, Martin [Charite Universitaetsmedizin Berlin, Academic Neuroradiology, Center for Stroke Research Berlin (CSB), Berlin (Germany); Charite Universitaetsmedizin, Department of Neurology, Berlin (Germany); Jungehuelsing, Gerhard J. [Stiftung des Buergerlichen Rechts, Juedisches Krankenhaus Berlin, Berlin (Germany)

2015-11-15

The hyperintense acute reperfusion marker (HARM) on fluid-attenuated inversion recovery (FLAIR) images is associated with blood-brain barrier (BBB) permeability changes. The aim of this study was to examine the influence of contrast agent dosage on HARM incidence in acute ischaemic stroke patients. We prospectively included 529 acute ischaemic stroke patients (204 females, median age 71 years). Patients underwent a first stroke-MRI within 24 hours from symptom onset and had a follow-up on day 2. The contrast agent Gadobutrol was administered to the patients for perfusion imaging or MR angiography. The total dosage was calculated as ml/kg body weight and ranged between 0.04 and 0.31 mmol/kg on the first examination. The incidence of HARM was evaluated on day 2 FLAIR images. HARM was detected in 97 patients (18.3 %). HARM incidence increased significantly with increasing dosages of Gadobutrol. Also, HARM positive patients were significantly older. HARM was not an independent predictor of worse clinical outcome, and we did not find an association with increase risk of haemorrhagic transformation. A higher dosage of Gadobutrol in acute stroke patients on initial MRI is associated with increased HARM incidence on follow-up. MRI studies on BBB should therefore standardize contrast agent dosages. (orig.)

Adrenal Insufficiency under Standard Dosage of Glucocorticoid Replacement after Unilateral Adrenalectomy for Cushing’s Syndrome

Directory of Open Access Journals (Sweden)

Kentaro Fujii

2016-01-01

Full Text Available 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.

Dosage Parameters in Pediatric Outcome Studies Reported in 9 Peer-Reviewed Occupational Therapy Journals from 2008 to 2014: A Content Analysis

Science.gov (United States)

Gee, Bryan M.; Lloyd, Kimberly; Devine, Nancy; Tyrrell, Erin; Evans, Trisha; Hill, Rebekah; Dineen, Stacee; Magalogo, Kristin

2016-01-01

Occupational therapists determine the dosage when establishing the plan of care for their pediatric clients. A content analysis was conducted using 123 pediatric occupational therapy outcomes studies from 9 scholarly international occupational therapy journals. The parameters of dosage were calculated using descriptive statistics in order to obtain a representation of dosage available within the current collage of pediatric occupational therapy outcomes studies. The results revealed that most studies reported portions of dosage parameters within the published studies. The average findings for the subcomponents related to dosage were session length (minutes) M = 58.7, duration of plan of care (weeks) M = 12.1, session frequency (per week) M = 3.4, and total hours of therapy (hours) M = 18.1. This first attempt at describing and calculating dosage related to pediatric occupational therapy practice indicates that evidence is lacking within the published literature to adequately guide OT dosage decisions. Further research related to dosage in pediatric occupational therapy practice is needed. PMID:26949547

Modifier Genes for Mouse Phosphatidylinositol Transfer Protein alpha (vibrator) That Bypass Juvenile Lethality

NARCIS (Netherlands)

Concepcion, Dorothy; Johannes, Frank; Lo, Yuan Hung; Yao, Jay; Fong, Jerry; Hamilton, Bruce A.

Phosphatidylinositol transfer proteins (PITPs) mediate lipid signaling and membrane trafficking in eukaryotic cells. Loss-of-function mutations of the gene encoding PITP alpha in mice result in a range of dosage-sensitive phenotypes, including neurological dysfunction, neurodegeneration, and

The characteristics of novel dosage forms

Directory of Open Access Journals (Sweden)

Milić-Aškrabić Jela

2003-01-01

Full Text Available The objective of pharmaceutical-technological development is to find a procedure of transforming an active substance (a drug into a drug dosage form which is not only acceptable for application, but also enables the active substance to be released following administration, pursuant to therapy objectives. The aim is that the concentration of the active substance in the action location rapidly reaches a therapeutic level and maintains an approximately constant level in the course of a particular time, according to the established therapeutic goal. The primary objective is to present the active ingredient (drug in the form and concentration/quantity that enables the corresponding therapeutic response, i.e. to control the site and rate of medicinal substance release from the drug, as well as the rate at which it reaches the membranes and surfaces to which it is absorbed, while applying a common method of administration. The procedures used to achieve this goal are becoming highly complex and demanding and are aiming at sophisticated drug delivery systems and functional packaging material. Development from the existing drug molecule, through the conventional drug dosage form, to a new system of drug "delivery" (novel delivery system, can improve the drug (active substance characteristics significantly in view of compliance (acceptability by the patient, safety and efficiency. The paper presents an overview of the most important examples of pharmaceutical forms with controlled release and advanced drug "carriers".

Dosage of DTPA administration by inhalation

International Nuclear Information System (INIS)

Koizumi, Akira; Fukuda, Satoshi; Yamada, Yuji; Iida, Haruzo; Shimo, Michikuni

2000-01-01

The administration of DTPA by inhalation was examined as an emergency medical treatment. In order to estimate the practical dosage to the human, an accurate model of the human air way was connected to a anesthetizer and respiration was simulated. Ca-DTPA, aerosolized by an ultra-sonic nebulizer, was administered by inhalation to the model. For the experiments, the respiratory volume (tidal volume) and the respiration rate was 12 per minute. Irrigation water from the model of larynx and mouth, and the air filter were collected and measured by chelate titration in order to determine the quantity of aerosolized DTPA and the amount deposited on the trachea and lang. The results indicated that the quantity of aerosolized DTPA varied with dilution of the DTPA solution in a ample. It was found that a 3 time dilution was the most practical and that 73 mg of DTPA per minute could be aerosolized. Furthermore, the results indicated that 46% of the aerosolized DTPA was taken in through inhalation and that 26% of DTPA was deposited in the trachea and lung. These results suggest that in practical application in the emergency medical treatment, 15 minutes of inhalation could delivered to approximately 500 mg of DTPA, and 130 mg could be delivered to the trachea and lung. It is considered that these quantity are enough amount to increase the effects of radioactive nuclides from the body, comparing with the recommended dosage for injection administration. (author)

Dosage of strontium 90 in human bone ashes; Dosage du strontium 90 sans les cendres d'os humain

Energy Technology Data Exchange (ETDEWEB)

Patti, F; Jeanmaire, L [Commissariat a l' Energie Atomique, Fontenay-aux-Roses (France). Centre d' Etudes Nucleaires

1964-07-01

The determination of {sup 90}Sr in bones by dosage of its daughter product {sup 90}Y is a 4-step process: 1) elimination of the phosphate ions by precipitation of the Ca and Sr as oxalate in the presence of acid; 2) reduction in the calcium concentration to a suitable level by the addition of a known volume of nitric acid (a single precipitation is sufficient), the precipitation yield of the strontium nitrate is checked by the measurement of the amount of {sup 85}Sr added as tracer; 3) purification by a yttrium hydroxide precipitation; 4) extraction at equilibrium of the {sup 90}Y which is counted to give the concentration. By using 50 gm of ash it is possible to detect about 0.1 pCi of {sup 90}Sr per gram of calcium. The advantages of this technique: -) treatment of a large quantity of bone ash -) the use of a small volume of nitric acid (less than 2 ml/g of ash, and -) the various operations present no difficulty. (authors) [French] Determination du Sr dans les os par dosage de son produit de filiation {sup 90}Y. Principe du dosage: 1 - Eliminer les ions phosphates par precipitation du calcium et du strontium sous forme d'oxalate en milieu acide. 2 - Reduire la concentration en calcium a un niveau convenable par addition d'un volume determine d'acide nitrique (une seule precipitation est necessaire). Le rendement de precipitation du nitrate de strontium est controle par la mesure de {sup 85}Sr ajoute comme traceur. 3 - Purifier par une precipitation d'hydroxyde d'yttrium. 4 - Extraire a l'equilibre l'{sup 90}Y qui eat compte pour determiner le {sup 90}Sr. En traitant 50 g de cendre, il est possible de deceler de l'ordre de 0,1 pCi de {sup 90}Sr par gramme de calcium. Les 3 avantages de cette technique: 1 - traitement d'une quantite importante de cendres d'os, 2 - emploi d'un faible volume d'acide nitrique (moins de 2 ml/g de cendres), et 3 - les diverses operations ne presentent aucune difficulte.

The Proximity of Ribosomal Protein Genes to oriC Enhances Vibrio cholerae Fitness in the Absence of Multifork Replication.

Science.gov (United States)

Soler-Bistué, Alfonso; Timmermans, Michaël; Mazel, Didier

2017-02-28

Recent works suggest that bacterial gene order links chromosome structure to cell homeostasis. Comparative genomics showed that, in fast-growing bacteria, ribosomal protein genes (RP) locate near the replication origin ( oriC ). We recently showed that Vibrio cholerae employs this positional bias as a growth optimization strategy: under fast-growth conditions, multifork replication increases RP dosage and expression. However, RP location may provide advantages in a dosage-independent manner: for example, the physical proximity of the many ribosomal components, in the context of a crowded cytoplasm, may favor ribosome biogenesis. To uncover putative dosage-independent effects, we studied isogenic V. cholerae derivatives in which the major RP locus, S10-spc-α (S10), was relocated to alternative genomic positions. When bacteria grew fast, bacterial fitness was reduced according to the S10 relative distance to oriC The growth of wild-type V. cholerae could not be improved by additional copies of the locus, suggesting a physiologically optimized genomic location. Slow growth is expected to uncouple RP position from dosage, since multifork replication does not occur. Under these conditions, we detected a fitness impairment when S10 was far from oriC Deep sequencing followed by marker frequency analysis in the absence of multifork replication revealed an up to 30% S10 dosage reduction associated with its relocation that closely correlated with fitness alterations. Hence, the impact of S10 location goes beyond a growth optimization strategy during feast periods. RP location may be important during the whole life cycle of this pathogen. IMPORTANCE The role of gene order within the bacterial chromosome is poorly understood. In fast growers, the location of genes linked with the expression of genetic information (i.e., transcription and translation) is biased toward oriC It was proposed that the location of these genes helps to maximize their expression by recruiting

Disposition Kinetics and Optimal Dosage of Ciprofloxacin in Healthy Domestic Ruminant Species

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Ijaz Javed

2009-01-01

Full Text Available The purpose of this experimental study was to determine the disposition kinetics and optimal dosages of ciprofloxacin in healthy domestic ruminant species including adult female buffalo, cow, sheep and goat. The drug was given as a single intramuscular dose of 5 mg/kg. The plasma concentrations of the drug were determined with HPLC and pharmacokinetic variables were determined. The biological half-life (t1/2 β was longer in cows (3.25 ± 0.46 h followed by intermediate values in buffaloes (3.05 ± 0.20 h and sheep (2.93 ± 0.45 h and shorter in goats (2.62 ± 0.39 h. The volume of distribution (Vd in buffaloes was 1.09 ± 0.06 l/kg, cows 1.24 ± 0.16 l/kg, sheep 2.89 ± 0.30 l/kg and goats 3.76 ± 0.92 l/kg. Total body clearance (ClB expressed in l/h/kg was minimum in buffaloes 0.25 ± 0.02 followed by values in cows 0.31 ± 0.02 and sheep 0.75 ± 0.04 and maximum in goats 1.09 ± 0.11. An optimal dosage regimen for 12-h interval consisted of 5.17, 5.62, 6.54 and 6.10 mg/kg body weight as priming and 4.84, 5.37, 6.26 and 5.91 mg/kg body weight as maintenance intramuscular dose in buffalo, cow, sheep and goat, respectively. The manufacturers of ciprofloxacin have claimed 5 mg/kg dose to be repeated after 24 h. However, the investigated dosage regimen may be repeated after 12 h to maintain MIC at the end of the dosage interval. Therefore, it is imperative that an optimal dosage regimen be based on the disposition kinetics data determined in the species and environment in which a drug is to be employed clinically.

Weakener of white (Wow), a gene that modifies the expression of the white eye color locus and that suppresses position effect variegation in Drosophila melanogaster.

Science.gov (United States)

Birchler, J A; Bhadra, U; Rabinow, L; Linsk, R; Nguyen-Huynh, A T

1994-08-01

A locus is described in Drosophila melanogaster that modifies the expression of the white eye color gene. This trans-acting modifier reduces the expression of the white gene in the eye, but elevates the expression in other adult tissues. Because of the eye phenotype in which the expression of white is lessened but not eliminated, the newly described locus is called the Weakener of white (Wow). Northern analysis reveals that Wow can exert an inverse or direct modifying effect depending upon the developmental stage. Two related genes, brown and scarlet, that are coordinately expressed with white, are also affected by Wow. In addition, Wow modulates the steady state RNA level of the retrotransposon, copia. When tested with a white promoter-Alcohol dehydrogenase reporter. Wow confers the modifying effect to the reporter, suggesting a requirement of the white regulatory sequences for mediating the response. In addition to being a dosage sensitive regulator of white, brown, scarlet and copia, Wow acts as a suppressor of position effect variegation. There are many dosage sensitive suppressors of position effect variegation and many dosage-sensitive modifiers of gene expression. The Wow mutations provide evidence for an overlap between the two types of modifiers.

Miniaturized approach for excipient selection during the development of oral solid dosage form

DEFF Research Database (Denmark)

Raijada, Dharaben Kaushikkumar; Müllertz, Anette; Cornett, Claus

2014-01-01

The present study introduces a miniaturized high-throughput platform to understand the influence of excipients on the performance of oral solid dosage forms during early drug development. Wet massing of binary mixtures of the model drug (sodium naproxen) and representative excipients was followed...... for excipient selection and for early-stage performance testing of active pharmaceutical ingredient intended for oral solid dosage form. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 103:900-908, 2014....

Gene dosage induction of silencing directed against an Arabidopsis Myb transgene in tobacco

Science.gov (United States)

An unexpected reduction in petal pigmentation on petunia plants genetically engineered for enhanced flower color was one of the first experimental demonstrations of the natural process of RNA-associated gene silencing. The obvious visual nature of such alterations to pigment patterns of transgenic ...

[The most effective dosage in the administration of PGF2-alpha for interruption of pregnancy during the 2d trimester].

Science.gov (United States)

Herczeg, J; Szontágh, F

1974-06-23

Artificial interruption of pregnancy contains too many risks from the 12th week of pregnancy. The authors have been working at finding the most suitable and effective dosage of prostaglandin for the interruption of pregnancy during the 2nd trimester. The new dosage experimented was 25 mg of prostaglandin F2alpha, followed by another 25 mg 6 hours later. The clinical efficiency of this dosage was tested. This procedures was used in 45 cases. The efficiency of the method was compared to the efficiency of the previously used dosage, which was 25 mg of prostaglandin F2alpha, followed by 25 mg 24 hours later. The new dosage was evaluated 91% efficient, while the previous dosage was found to be 75% efficient. The side effects were rated as acceptable by the patients. There was no case of infection. Two undeniable advantages were found with this new dosage: the duration of the actual procedure is considerably reduced, and the method appears to be much safer. The authors conclude that this new procedure offers numerous clinical advantages.

Study on image quality and dosage comparison of F/S system and DR system

International Nuclear Information System (INIS)

Kim, Sun Chil; Jung, Jae Eun

2003-01-01

Currently, many hospital are hastening to introduce digital radiography systems. This is a direct result of the intentions to improve medical services and to digitalized radiology information systems, and is also leading to the improvement of medical imaging technology. Throughout F/S system's long history, many people have researched the image quality and dosage concerning these systems, and as a result, huge improvements in the dosage of patients were possible. Similarly, I believe that DR systems need the same kind of effort. Of course, decreases in dosage that ignore image quality are unthinkable. The results of experiments conducted by five hospitals during a period of 3 months brought to us the conclusions listed below. Based on the comparison and analysis of the exposure control of F/S systems and DR systems, DR systems generally showed higher exposure control for parts of the phantom that became thicker, and the exposure control improved rapidly as the thickness increased. DR systems still proved to be somewhat deficient in resolution measurements compared to existing F/S systems. The image processing part of DR systems contributed much to these result. Under conditions used clinically, the dosage measurements of DR systems were generally higher regardless of region. According to the evaluation of image quality, DR systems showed a higher degree of satisfaction as the thickness of the region became thinner. As mentioned above and based on the mutual relationship experiments between the dosage and image quality of F/S systems and DR systems, research to increase the satisfaction of DR systems must be considered

Gonadal dosage during hip dysplasia radiography in the dog.

Science.gov (United States)

Wood, A K; Reynolds, K M; Leith, I S; Burns, P A

1977-01-01

Thermoluminescent dosemeters were used to estimate gonadal dosage during hip dysplasia radiography of labrador retriever dogs. The mean radiation dose to the unshielded testes was 100 millirad (mrad) and the estimated dose to the shielded testes was 9 mrad. It was considered unnecessary to shield the ovaries.

Gamma ray dosage and mutation breeding in St. Augustinegrass

International Nuclear Information System (INIS)

Busey, P.

1980-01-01

Stolon pieces of St. Augustinegrass [Stenotaphrum secundatum (Walt.) Kuntze] were irradiated with gamma rays in an attempt to cause mutations. A practical dosage for most genotypes was 4,500 rads. This dosage caused considerable (50%) growth retardation and a mean survival of about 40% of single-node cuttings. However, Bitterblue and another accession were entirely killed at 4,000 rads. At 4,500 rads, up to 7% recognizable mutants of accession FA-243 were obtained. This proportion resulted when irradiated cuttings were propagated clonally and observed for 1.5 years in replicated microplots. In addition to morphological variants, a chimeral anthocyanin change was noticed. From this chimera arose a stable genotype with green stolons and white stigmas, whereas the source genotype (FA-243) had red stolons and purple stigmas. Associated reduction in fertility from 56 to 0.6% suggested that the mutation arose as a small chromosome deletion. Mutation breeding is effective in improving St. Augustinegrass when easily recognizable variants are needed

Absorption of macronutrients by cassava in different harvest dates and dosages of nitrogen

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Nádia Souza dos Santos

Full Text Available A field experiment was carried out in 2010-2011 crop years in the experimental area of the Centro de Ciências Agrárias of the Universidade Federal de Roraima, in Boa Vista, Roraima, Brazil. This study aimed to evaluate the effect of nitrogen availability on the concentrations of N, P, K, Ca, Mg and S in cassava, cultivar Aciolina, in different harvest times. A randomized block design was used in split-plot, with four replications. Dosages of N in cover were applied randomly on the plots (0, 30, 60, 150 and 330 kg ha-1, and in the subplot the harvest dates 120, 150, 180, 210, 240, 270 and 300 days after emergence (DAE. The vegetal material was collected, ground and then underwent an analysis for determination of nutrients concentrations in the leaves (N, P, K, Ca Mg and S. The harvest dates and dosages of N affect the nutrient concentrations in the cassava leaves, cv. Aciolina. The macronutrients dosage in the leaves, 120 DAE, is a good indicator of the nutritional status of the cassava plant. The dosage of 150 kg ha-1 of N raises the tubers roots per plant. The sequence of the macronutrients concentration in the leaves of the cassava, cv. Aciolina is N>Ca>K>Mg>P>S.

Optimal Antibiotic Dosage for Chronic Kidney Disease Patient: A Pharmacological Manual for Oral Clinicians.

Science.gov (United States)

Chidambaram, Ramasamy

2015-01-01

Chronic kidney disease, (CKD) a gradual and inevitable deterioration in renal function, is the disease with the most associations in dentistry. Dosage adjustment is one amongst the vital elements to be familiar with during their oral care. CKD patients take extended duration to filter out medications, therefore dosage must always be tailored under the supervision of nephrologist. The relished benefits from antibiotic could transform as anti-microbial resistance on their abuse and nephrotoxic when contraindicated drugs are encouraged. New patented drug belonging to oxazoliodine group has driven the researchers to handle the emerging AMR. The present communication discusses the pharmacological factors influencing in prescribing the antibiotics for CKD patient from the dentist's point of view. The formulas destined for calculating the optimal dosage of antibiotics have been documented to aid oral physicians.

Characterisation of lung tumour under dosage for interpretation of clinical trial data

International Nuclear Information System (INIS)

Taylor, M.L.; Dunn, L.; Franich, R.D.; Kron, T.; Height, F.

2010-01-01

Full text: It is well known that the periphery of lung tumours is under-dosed in radiotherapy as a result of electronic disequilibrium at the interface of lung and tumour tissue. Clinical trials often employ dose calculation algorithms which poorly approximate the dose to peripheral regions of tumour volumes. The aim of this study was to develop a set of systematic under-dosage estimates corresponding to various clinical parameters. High resolution Monte Carlo radiation transport calculations were undertaken for a systematic set of generic lung tumours irradiated with an external photon beam. Varied parameters include beam energy, field size, tumour size and distance to chest wall. Calculations were undertaken using both EGSnrc and GEAI T4. A 'Dose Reduction Factor' is defined which describes the dose to the peripheral 'shell' 01 the tumour, as relevant for multiple-field and arc therapy. For a 6 MV beam, under-dosage is typically between 2 and 5% for the different arrangements investigated, and for a 15 MV beam it is between 5 and 8% (relative to the central dose). Good agreement between EGSnrc and GEANT4 was demonstrated. Comparisons with pencil beam convolution calculations indicate that the treatment planning system does not identify this under-dosage. A systematic set of data has been obtained that characterises the extent of peripheral under-dosage in lung tumours for the retrospective evaluation of clinical trial data. The data presented i: also informative for clinics using less sophisticated planning algorithms, particularly when dose is being prescribed to covering isodoses. (author)

Influence of Postprandial Intragastric Pressures on Drug Release from Gastroretentive Dosage Forms.

Science.gov (United States)

Schneider, Felix; Hoppe, Melanie; Koziolek, Mirko; Weitschies, Werner

2018-05-29

Despite extensive research in the field of gastroretentive dosage forms, this "holy grail" of oral drug delivery yet remained an unmet goal. Especially under fasting conditions, the reproducible retention of dosage forms in the stomach seems to be an impossible task. This is why such systems are often advised to be taken together with food. But also the postprandial motility can contribute significantly to the failure of gastroretentive dosage forms. To investigate the influence of postprandial pressure conditions on drug release from such systems, we used a novel in vitro dissolution tool, the dissolution stress test device. With the aid of this device, we simulated three different intragastric pressure profiles that may occur after postprandial intake. These transit scenarios were based on recently obtained, postprandial SmartPill® data. The tested systems, Glumetza® 1000 and Madopar® HBS 125, are marketed dosage forms that are based on different approaches to achieve proper gastric retention. All three transit scenarios revealed a highly pressure-sensitive drug release behavior, for both drugs. For Madopar® HBS 125, nearly complete drug release was observed even after early occurring pressures. Glumetza® 1000 seemed to be more resistant to these, most likely due to incomplete wetting of the system. On the contrary to these findings, data from standard dissolution tests using the paddle apparatus displayed controlled drug release for both systems for about 6 h. Based on these results, it can be doubted that established gastroretentive systems stay intact over a longer period of time, even under postprandial conditions.

Contemporary Animal Models For Human Gene Therapy Applications.

Science.gov (United States)

Gopinath, Chitra; Nathar, Trupti Job; Ghosh, Arkasubhra; Hickstein, Dennis Durand; Nelson, Everette Jacob Remington

2015-01-01

Over the past three decades, gene therapy has been making considerable progress as an alternative strategy in the treatment of many diseases. Since 2009, several studies have been reported in humans on the successful treatment of various diseases. Animal models mimicking human disease conditions are very essential at the preclinical stage before embarking on a clinical trial. In gene therapy, for instance, they are useful in the assessment of variables related to the use of viral vectors such as safety, efficacy, dosage and localization of transgene expression. However, choosing a suitable disease-specific model is of paramount importance for successful clinical translation. This review focuses on the animal models that are most commonly used in gene therapy studies, such as murine, canine, non-human primates, rabbits, porcine, and a more recently developed humanized mice. Though small and large animals both have their own pros and cons as disease-specific models, the choice is made largely based on the type and length of study performed. While small animals with a shorter life span could be well-suited for degenerative/aging studies, large animals with longer life span could suit longitudinal studies and also help with dosage adjustments to maximize therapeutic benefit. Recently, humanized mice or mouse-human chimaeras have gained interest in the study of human tissues or cells, thereby providing a more reliable understanding of therapeutic interventions. Thus, animal models are of great importance with regard to testing new vector technologies in vivo for assessing safety and efficacy prior to a gene therapy clinical trial.

Formulation and evaluation of tablet dosage form of Hunteria ...

African Journals Online (AJOL)

The present study was aimed at formulating and evaluating tablet dosage form of Hunteria umbellata (HU) seed aqueous and purified extracts. HU seeds were dried, pulverized and the powder macerated in water to obtain aqueous extract, while alkaloidal extraction process was used to obtain purified extract. Extracts ...

Dropwise additive manufacturing of pharmaceutical products for solvent-based dosage forms.

Science.gov (United States)

Hirshfield, Laura; Giridhar, Arun; Taylor, Lynne S; Harris, Michael T; Reklaitis, Gintaras V

2014-02-01

In recent years, the US Food and Drug Administration has encouraged pharmaceutical companies to develop more innovative and efficient manufacturing methods with improved online monitoring and control. Mini-manufacturing of medicine is one such method enabling the creation of individualized product forms for each patient. This work presents dropwise additive manufacturing of pharmaceutical products (DAMPP), an automated, controlled mini-manufacturing method that deposits active pharmaceutical ingredients (APIs) directly onto edible substrates using drop-on-demand (DoD) inkjet printing technology. The use of DoD technology allows for precise control over the material properties, drug solid state form, drop size, and drop dynamics and can be beneficial in the creation of high-potency drug forms, combination drugs with multiple APIs or individualized medicine products tailored to a specific patient. In this work, DAMPP was used to create dosage forms from solvent-based formulations consisting of API, polymer, and solvent carrier. The forms were then analyzed to determine the reproducibility of creating an on-target dosage form, the morphology of the API of the final form and the dissolution behavior of the drug over time. DAMPP is found to be a viable alternative to traditional mass-manufacturing methods for solvent-based oral dosage forms. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association.

Identification and analcime quantification; Identification et dosage de l'analcime

Energy Technology Data Exchange (ETDEWEB)

Chantret, F; Guillemaut, A; Pouget, R

1962-07-01

The authors are comparing thermal analysis and X-ray diffraction methods for the estimation of analcime in rocks. From application to the analcimolithes of Agades - Republic of Niger - it appears that X-ray diffractometry is better convenient, both for identification and estimation; nevertheless, thermal analysis combined with chemical analysis allows to detect variations in the composition of analcime inside a given series. [French] Les auteurs comparent les techniques d'analyse thermique et de diffraction X pour le dosage de l'analcime dans les roches. L'application aux analcimolites d'Agades - Republique du Niger - montre que la diffractometrie X est mieux adaptee a la fois dans l'identification et le dosage; neanmoins, l'analyse thermique, associee a l'analyse chimique, permet de suivre les fluctuations de composition de l'analcime a l'interieur d'une serie determinee. (auteurs)

Fuzzy-based dosage model of aqueous decoction of Adansonia ...

African Journals Online (AJOL)

However, in the area of traditional medicine, no much attention has been given to its enhancement with the use of information technology especially in the area of herbal prescription. ... The mass of herb and volume of solvent were used as input parameters to design the dosage model, and simulated using MATLAB.

Genome-Wide Gene Expression Disturbance by Single A1/C1 Chromosome Substitution in Brassica rapa Restituted From Natural B. napus

Directory of Open Access Journals (Sweden)

Bin Zhu

2018-03-01

Full Text Available Alien chromosome substitution (CS lines are treated as vital germplasms for breeding and genetic mapping. Previously, a whole set of nine Brassica rapa-oleracea monosonic alien addition lines (MAALs, C1-C9 was established in the background of natural B. napus genotype “Oro,” after the restituted B. rapa (RBR for Oro was realized. Herein, a monosomic substitution line with one alien C1 chromosome (Cs1 in the RBR complement was selected in the progenies of MAAL C1 and RBR, by the PCR amplification of specific gene markers and fluorescence in situ hybridization. Cs1 exhibited the whole plant morphology similar to RBR except for the defective stamens without fertile pollen grains, but it produced some seeds and progeny plants carrying the C1 chromosome at high rate besides those without the alien chromosome after pollinated by RBR. The viability of the substitution and its progeny for the RBR diploid further elucidated the functional compensation between the chromosome pairs with high homoeology. To reveal the impact of such aneuploidy on genome-wide gene expression, the transcriptomes of MAAL C1, Cs1 and euploid RBR were analyzed. Compared to RBR, Cs1 had sharply reduced gene expression level across chromosome A1, demonstrating the loss of one copy of A1 chromosome. Both additional chromosome C1 in MAAL and substitutional chromosome C1 in Cs1 caused not only cis-effect but also prevalent trans-effect differentially expressed genes. A dominant gene dosage effects prevailed among low expressed genes across chromosome A1 in Cs1, and moreover, dosage effects for some genes potentially contributed to the phenotype deviations. Our results provided novel insights into the transcriptomic perturbation and gene dosage effects on phenotype in CS related to one naturally evolved allopolyploid.

The effect of decreasing computed tomography dosage on radiostereometric analysis (RSA) accuracy at the glenohumeral joint.

Science.gov (United States)

Fox, Anne-Marie V; Kedgley, Angela E; Lalone, Emily A; Johnson, James A; Athwal, George S; Jenkyn, Thomas R

2011-11-10

Standard, beaded radiostereometric analysis (RSA) and markerless RSA often use computed tomography (CT) scans to create three-dimensional (3D) bone models. However, ethical concerns exist due to risks associated with CT radiation exposure. Therefore, the aim of this study was to investigate the effect of decreasing CT dosage on RSA accuracy. Four cadaveric shoulder specimens were scanned using a normal-dose CT protocol and two low-dose protocols, where the dosage was decreased by 89% and 98%. 3D computer models of the humerus and scapula were created using each CT protocol. Bi-planar fluoroscopy was used to image five different static glenohumeral positions and two dynamic glenohumeral movements, of which a total of five static and four dynamic poses were selected for analysis. For standard RSA, negligible differences were found in bead (0.21±0.31mm) and bony landmark (2.31±1.90mm) locations when the CT dosage was decreased by 98% (p-values>0.167). For markerless RSA kinematic results, excellent agreement was found between the normal-dose and lowest-dose protocol, with all Spearman rank correlation coefficients greater than 0.95. Average root mean squared errors of 1.04±0.68mm and 2.42±0.81° were also found at this reduced dosage for static positions. In summary, CT dosage can be markedly reduced when performing shoulder RSA to minimize the risks of radiation exposure. Standard RSA accuracy was negligibly affected by the 98% CT dose reduction and for markerless RSA, the benefits of decreasing CT dosage to the subject outweigh the introduced errors. Copyright © 2011 Elsevier Ltd. All rights reserved.

Determination of the Minimum Effective Dosages of Praziquantel, Albendazole, and Mebendazole Against Clonorchis Sinensis Infection in Rats

Directory of Open Access Journals (Sweden)

Ping-Chin Fan

2005-10-01

Full Text Available In order to determine the minimum effective dosages of praziquantel, albendazole, and mebendazole against Clonorchis sinensis infection in Sprague-Dawley rats, each rat was infected with 30 metacercariae and treated with one of three drugs. The rats were killed and examined 25 days after praziquantel treatment or 11 days after albendazole or mebendazole treatment. The minimum effective dosages were a single dose of praziquantel 375 mg/kg, albendazole 150 mg/kg, and mebendazole 150 mg/kg. Trials are required to determine whether these dosages are useful in the treatment of human clonorchiasis.

[Molecular mechanisms in sex determination: from gene regulation to pathology].

Science.gov (United States)

Ravel, C; Chantot-Bastaraud, S; Siffroi, J-P

2004-01-01

Testis determination is the complex process by which the bipotential gonad becomes a normal testis during embryo development. As a consequence, this process leads to sexual differentiation corresponding to the masculinization of both genital track and external genitalia. The whole phenomenon is under genetic control and is particularly driven by the presence of the Y chromosome and by the SRY gene, which acts as the key initiator of the early steps of testis determination. However, many other autosomal genes, present in both males and females, are expressed during testis formation in a gene activation pathway, which is far to be totally elucidated. All these genes act in a dosage-sensitive manner by which quantitative gene abnormalities, due to chromosomal deletions, duplications or mosaicism, may lead to testis determination failure and sex reversal.

Dosage of fission products in irradiated fuel treatment effluents (radio-chemical method); Dosage des produits de fission dans les effluents du traitement des combustibles irradies (methode radiochimique)

Energy Technology Data Exchange (ETDEWEB)

Auchapt, J [Commissariat a l' Energie Atomique, Marcoule (France). Centre d' Etudes Nucleaires

1966-07-01

The dosage methods presented here are applicable to relatively long-lived fission products present in the effluents resulting from irradiated fuel treatment processes (Sr - Cs - Ce - Zr - Nb - Ru - I). The methods are based on the same principle: - addition of a carrying-over agent - chemical separation over several purification stages, - determination of the chemical yield by calorimetry - counting of an aliquot liquid portion. (author) [French] Les methodes de dosage presentees concernent les produits de fission a vie relativement longue presents dans les effluents de traitement des combustibles irradies (Sr - Cs - Ce - Zr - Nb - Ru - I). Elles sont toutes basees sur le meme principe: - addition d'entraineur, - separation chimique en plusieurs stades de purification, - determination du rendement chimique par calorimetrie, - comptage d'une aliquote liquide. (auteur)

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

NARCIS (Netherlands)

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

2006-01-01

Literature data relevant to the decision to allow a waiver of in vivo bioequivalence (BE) testing for the approval of immediate release (IR) solid oral dosage forms containing cimetidine are reviewed. According to the current Biopharmaceutics Classification System (BCS), cimetidine would be assigned

Determination of methadone hydrochloride in a maintenance dosage formulation.

Science.gov (United States)

Hoffmann, T J; Thompson, R D

1975-07-01

A colorimetric method for direct quantitative assay of methadone hydrochloride in liquid oral dosage forms is presented. The procedure involves the formation of a dye complex with bromothymol blue buffer solution. The resultant complex is extracted with benzene and measured spectrophotometrically. Duplicate tests on the formulation showed 99.2% of the labeled amount of methadone.

Formulation of Croton penduliflorus seed into tablet dosage form ...

African Journals Online (AJOL)

Formulation of Croton penduliflorus seed into tablet dosage form. GC Onunkwo. Abstract. No Abstract. Global Journal of Medical Sciences Vol. 5(1) 2006: 29-33. Full Text: EMAIL FREE FULL TEXT EMAIL FREE FULL TEXT · DOWNLOAD FULL TEXT DOWNLOAD FULL TEXT · http://dx.doi.org/10.4314/gjms.v5i1.10145.

In situ experimental study for the optimization of chlorine dosage in seawater cooling systems

Energy Technology Data Exchange (ETDEWEB)

Nebot, E.; Casanueva, T.; Fernandez-Baston, M.M.; Sales, D. [Department of Chemical Engineering, Food Technology and Environmental Technologies, University of Cadiz (Spain); Casanueva, J.F. [Department of Thermal Engines, University of Cadiz (Spain)

2006-11-15

The paper details an in situ study for the evaluation of the evolution of fouling heat transfer resistance and to optimize the antifouling chlorine dosage at a 550MW power station. A portable pilot plant has been designed to simulate the steam surface condenser and used as an accurate fouling monitor that takes the seawater from the same intake point as the power station. This study includes fouling extraction and its characterization for different dosage patterns. The residual chlorine concentration at the cooling-water discharge from the power station is 0.2mg/l and has been considered appropriate for the prevention of the formation of fouling, because with this concentration approximately 90% reduction in the amount of fouling is obtained. Residual chlorine dosages lower than 0.2ppm could be effective in controlling fouling development if mechanical techniques of fouling control are also available. (author)

Unilateral brief-pulse electroconvulsive therapy and cognition: Effects of electrode placement, stimulus dosage and time.

LENUS (Irish Health Repository)

Semkovska, Maria

2010-11-23

To clarify advantages of unilateral electrode placement as an optimisation technique for electroconvulsive therapy (ECT) for depression, aims were to meta-analyse unilateral ECT effects on cognitive performance relative to: (1) bitemporal electrode placement, (2) electrical dosage, and (3) time interval between final treatment and cognitive reassessment. Relevant electronic databases were systematically searched through May 2009, using the terms: "electroconvulsive therapy" and ["cogniti∗", "neuropsycholog∗", "memory", "attention", "executive", "spatial", or "intellectual"]. Inclusion criteria were: independent study of depressed patients receiving unilateral or bitemporal brief-pulse ECT; within-subjects design; use of objective cognitive assessments; available mean electrical dosage for unilateral samples. Standardized pre-post ECT weighted effect sizes were computed and pooled within 16 cognitive domains by a mixed-effects model. Thirty-nine studies (1415 patients) were meta-analysed. Up to three days after final treatment, unilateral ECT was associated with significantly smaller decreases in global cognition, delayed verbal memory retrieval, and autobiographical memory, compared to bitemporal ECT. Significant publication bias was found for autobiographical memory, favouring reporting of larger percentage loss. Higher unilateral ECT electrical dosage predicted larger decreases in verbal learning, delayed verbal memory retrieval, visual recognition, and semantic memory retrieval. When retested more than three days after completing ECT, no significant differences remained between the two electrode placements; for unilateral ECT, electrical dosage no longer predicted cognitive performance whereas increasing interval between final treatment and retesting predicted growing improvement in some variables. This interval is a more useful long-term predictor of cognitive function than electrode placement or electrical dosage following unilateral ECT.

Unilateral brief-pulse electroconvulsive therapy and cognition: effects of electrode placement, stimulus dosage and time.

Science.gov (United States)

Semkovska, Maria; Keane, Deborah; Babalola, Oyemi; McLoughlin, Declan M

2011-06-01

To clarify advantages of unilateral electrode placement as an optimisation technique for electroconvulsive therapy (ECT) for depression, aims were to meta-analyse unilateral ECT effects on cognitive performance relative to: (1) bitemporal electrode placement, (2) electrical dosage, and (3) time interval between final treatment and cognitive reassessment. Relevant electronic databases were systematically searched through May 2009, using the terms: "electroconvulsive therapy" and ["cogniti∗", "neuropsycholog∗", "memory", "attention", "executive", "spatial", or "intellectual"]. Inclusion criteria were: independent study of depressed patients receiving unilateral or bitemporal brief-pulse ECT; within-subjects design; use of objective cognitive assessments; available mean electrical dosage for unilateral samples. Standardized pre-post ECT weighted effect sizes were computed and pooled within 16 cognitive domains by a mixed-effects model. Thirty-nine studies (1415 patients) were meta-analysed. Up to three days after final treatment, unilateral ECT was associated with significantly smaller decreases in global cognition, delayed verbal memory retrieval, and autobiographical memory, compared to bitemporal ECT. Significant publication bias was found for autobiographical memory, favouring reporting of larger percentage loss. Higher unilateral ECT electrical dosage predicted larger decreases in verbal learning, delayed verbal memory retrieval, visual recognition, and semantic memory retrieval. When retested more than three days after completing ECT, no significant differences remained between the two electrode placements; for unilateral ECT, electrical dosage no longer predicted cognitive performance whereas increasing interval between final treatment and retesting predicted growing improvement in some variables. This interval is a more useful long-term predictor of cognitive function than electrode placement or electrical dosage following unilateral ECT. Copyright © 2010

Stability of pharmaceutical salts in solid oral dosage forms.

Science.gov (United States)

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

2017-08-01

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

Simultaneous in vivo visualization and localization of solid oral dosage forms in the rat gastrointestinal tract by magnetic resonance imaging (MRI).

Science.gov (United States)

Christmann, V; Rosenberg, J; Seega, J; Lehr, C M

1997-08-01

Bioavailability of orally administered drugs is much influenced by the behavior, performance and fate of the dosage form within the gastrointestinal (GI) tract. Therefore, MRI in vivo methods that allow for the simultaneous visualization of solid oral dosage forms and anatomical structures of the GI tract have been investigated. Oral contrast agents containing Gd-DTPA were used to depict the lumen of the digestive organs. Solid oral dosage forms were visualized in a rat model by a 1H-MRI double contrast technique (magnetite-labelled microtablets) and a combination of 1H- and 19F-MRI (fluorine-labelled minicapsules). Simultaneous visualization of solid oral dosage forms and the GI environment in the rat was possible using MRI. Microtablets could reproducibly be monitored in the rat stomach and in the intestines using a 1H-MRI double contrast technique. Fluorine-labelled minicapsules were detectable in the rat stomach by a combination of 1H- and 19F-MRI in vivo. The in vivo 1H-MRI double contrast technique described allows solid oral dosage forms in the rat GI tract to be depicted. Solid dosage forms can easily be labelled by incorporating trace amounts of non-toxic iron oxide (magnetite) particles. 1H-MRI is a promising tool for observing such pharmaceutical dosage forms in humans. Combined 1H- and 19F-MRI offer a means of unambiguously localizing solid oral dosage forms in more distal parts of the GI tract. Studies correlating MRI examinations with drug plasma levels could provide valuable information for the development of pharmaceutical dosage forms.

[Development and effectiveness of a drug dosage calculation training program using cognitive loading theory based on smartphone application].

Science.gov (United States)

Kim, Myoung Soo; Park, Jung Ha; Park, Kyung Yeon

2012-10-01

This study was done to develop and evaluate a drug dosage calculation training program using cognitive loading theory based on a smartphone application. Calculation ability, dosage calculation related self-efficacy and anxiety were measured. A nonequivalent control group design was used. Smartphone application and a handout for self-study were developed and administered to the experimental group and only a handout was provided for control group. Intervention period was 4 weeks. Data were analyzed using descriptive analysis, χ²-test, t-test, and ANCOVA with the SPSS 18.0. The experimental group showed more 'self-efficacy for drug dosage calculation' than the control group (t=3.82, psmartphone application is effective in improving dosage calculation related self-efficacy and calculation ability. Further study should be done to develop additional interventions for reducing anxiety.

Dosage plasmatique et globulaire du magnesium dans l'exploration ...

African Journals Online (AJOL)

Objectives: The allergic rhinitis represents a real public health problem. The goal of this survey is to value the interest of the dosage plasmatical and globular of magnesium in the diagnosis of the allergic rhinitis. Materials and methods : Analytic and prospective survey of 80 files, on one period of 4 years and 5 months (from ...

Dosage of cesium 137 in radioactive wastes by the application of sodium tetraphenylborate; Dosage du cesium 137 dans les effluents radioactifs par le tetraphenylborate de sodium

Energy Technology Data Exchange (ETDEWEB)

Testemale, G; Girault, J [Commissariat a l' Energie Atomique, Fontenay-aux-Roses (France). Centre d' Etudes Nucleaires

1967-07-01

A simple technique of the dosage of {sup 137}Cs has been developed. The technique consists in the formation of cesium tetraphenyl borate, followed by a double extraction with isoamyl acetate, and washing of the organic phase. The counting of known parts of the cesium solution assaying of its purity by {gamma} spectrometry enable the determination of the {sup 137}Cs. The yield is about 98 per cent. (authors) [French] Une technique simple du dosage du {sup 137}Cs a ete mise au point. Elle consiste en une double extraction du tetraphenylborate de cesium forme par l'acetate d'isoamyle suivie d'un lavage de la phase organique. Des comptages sur des parties aliquotes de la solution de cesium et un controle de purete par spectrometrie {gamma} permettent la determination de cet element. Rendement: environ 98 pour cent. (auteurs)

Age- and Gene-Dosage–Dependent Cre-Induced Abnormalities in the Retinal Pigment Epithelium

Science.gov (United States)

He, Lizhi; Marioutina, Mariya; Dunaief, Joshua L.; Marneros, Alexander G.

2015-01-01

To conditionally inactivate genes in the retinal pigment epithelium (RPE) transgenic mouse strains have been developed, in which Cre recombinase (Cre) expression is driven by an RPE-specific gene promoter. The RPE is a quiescent epithelium, and continuous expression of Cre could affect its function. Here, we tested the hypothesis that continuous postnatal Cre expression in the RPE may lead to cellular abnormalities, which may depend on both age and Cre gene dosage. We therefore examined the eyes of homozygous and heterozygous VMD2-Cre mice at various ages. In VMD2-Cre heterozygous mice variable progressive age-dependent RPE abnormalities were noticed, including attenuation of phalloidin and cytoplasmic active β-catenin staining, reduced cell size, and loss of the typical honeycomb pattern of RPE morphology in those RPE cells that stained for Cre. These morphological RPE abnormalities were not noticed in Cre-negative RPE cells in VMD2-Cre or age-matched control mice. In addition, an abnormal number and morphology of cell nuclei were noticed in a subset of Cre-expressing RPE cells in aged heterozygous VMD2-Cre mice, whereas more severe nuclear abnormalities were observed already in young homozygous VMD2-Cre mice. Thus, continuous postnatal expression of Cre causes abnormalities in the RPE in an age- and Cre gene dosage-dependent manner, which needs to be considered in the interpretation of gene targeting studies in the RPE. PMID:24854863

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

Science.gov (United States)

2011-09-23

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Part 520 [Docket No. FDA-2011-N-0003] Oral Dosage Form New Animal Drugs; Tylosin AGENCY: Food and Drug Administration, HHS. ACTION: Final rule. SUMMARY: The Food and Drug Administration (FDA) is amending the animal drug...

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

Science.gov (United States)

2012-01-26

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Part 520 [Docket No. FDA-2011-N-0003] Oral Dosage Form New Animal Drugs; Deracoxib AGENCY: Food and Drug Administration, HHS. ACTION: Final rule. SUMMARY: The Food and Drug Administration (FDA) is amending the animal drug...

76 FR 18648 - Oral Dosage Form New Animal Drugs; Robenacoxib

Science.gov (United States)

2011-04-05

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Part 520 [Docket No. FDA-2011-N-0003] Oral Dosage Form New Animal Drugs; Robenacoxib AGENCY: Food and Drug Administration, HHS. ACTION: Final rule. SUMMARY: The Food and Drug Administration (FDA) is amending the animal drug...

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

Science.gov (United States)

2011-07-12

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Part 520 [Docket No. FDA-2011-N-0003] Oral Dosage Form New Animal Drugs; Amprolium AGENCY: Food and Drug Administration, HHS. ACTION: Final rule. SUMMARY: The Food and Drug Administration (FDA) is amending the animal drug...

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

Science.gov (United States)

2012-03-19

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Part 520 [Docket No. FDA-2011-N-0003] Oral Dosage Form New Animal Drugs; Pergolide AGENCY: Food and Drug Administration, HHS. ACTION: Final rule. SUMMARY: The Food and Drug Administration (FDA) is amending the animal drug...

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

Science.gov (United States)

2010-11-01

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Part 520 [Docket No. FDA-2010-N-0002] Oral Dosage Form New Animal Drugs; Domperidone AGENCY: Food and Drug Administration, HHS. ACTION: Final rule. SUMMARY: The Food and Drug Administration (FDA) is amending the animal drug...

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

Science.gov (United States)

2011-12-16

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Part 520 [Docket No. FDA-2011-N-0003] Oral Dosage Form New Animal Drugs; Estriol AGENCY: Food and Drug Administration, HHS. ACTION: Final rule. SUMMARY: The Food and Drug Administration (FDA) is amending the animal drug...

Applications of Polymers as Pharmaceutical Excipients in Solid Oral Dosage Forms.

Science.gov (United States)

Debotton, Nir; Dahan, Arik

2017-01-01

Over the last few decades, polymers have been extensively used as pharmaceutical excipients in drug delivery systems. Pharmaceutical polymers evolved from being simply used as gelatin shells comprising capsule to offering great formulation advantages including enabling controlled/slow release and specific targeting of drugs to the site(s) of action (the "magic bullets" concept), hence hold a significant clinical promise. Oral administration of solid dosage forms (e.g., tablets and capsules) is the most common and convenient route of drug administration. When formulating challenging molecules into solid oral dosage forms, polymeric pharmaceutical excipients permit masking undesired physicochemical properties of drugs and consequently, altering their pharmacokinetic profiles to improve the therapeutic effect. As a result, the number of synthetic and natural polymers available commercially as pharmaceutical excipients has increased dramatically, offering potential solutions to various difficulties. For instance, the different polymers may allow increased solubility, swellability, viscosity, biodegradability, advanced coatings, pH dependency, mucodhesion, and inhibition of crystallization. The aim of this article is to provide a wide angle prospect of the different uses of pharmaceutical polymers in solid oral dosage forms. The various types of polymeric excipients are presented, and their distinctive role in oral drug delivery is emphasized. The comprehensive know-how provided in this article may allow scientists to use these polymeric excipients rationally, to fully exploit their different features and potential influence on drug delivery, with the overall aim of making better drug products. © 2016 Wiley Periodicals, Inc.

Age and dosage-level dependence of radium retention in beagles

International Nuclear Information System (INIS)

Parks, N.J.; Pool, R.R.; Williams, J.R.; Wolf, H.G.

1978-01-01

Radium retention was measured over the lifespan of 46 beagles exposed by eight semimonthly injections at 60 to 160, 120 to 220, or 435 to 535 days of age. Injection dosage levels ranged from 0.37 to 10 μCi of 226 Ra/kg. The fractional retention of each animal is described in terms of a modified power function, R = [(t + d)/d] - /sup b/. Young adult beagles (approximately equal to 10 kg) injected at a mean age (A) of 485 days with 226 Ra at dosage levels of 10, 3.3, 1.11, and 0.37 μCi/kg had mean values for d and b of [0.897; 0.187], [2.015; 0.206], [2.778; 0.257], and [3.894; 0.274], respectively. Juvenile beagles injected with 10 μCi/kg at A = 110 days (average weight approximately equal to 6 kg) and at A = 170 days (average weight approximately equal to 10 kg) had mean values for d and b of [137; 0.277] and [5.53; 0.086], respectively. The d values are geometric means and the units are days; b values are arithmetic means. The formula for deriving the age-dependent retention function for dogs is given. The beagle results were correlated with human data in terms of age-to-equivalent fraction of adult body calcium content and were used to construct a similar age-dependent retention function for chronically exposed people. The correlation of age-dependent retention functions for beagles and humans is used to estimate scaling factors between the two species for the fraction of injected dosage associated with bone for various ages of exposure

Dosage of trace carbon in sodium (1963); Dosage de traces de carbone dans le sodium (1963)

Energy Technology Data Exchange (ETDEWEB)

Sannier, J; Vasseur, A [Commissariat a l' Energie Atomique, Saclay (France). Centre d' Etudes Nucleaires

1963-07-01

A wet method for dosing carbon in sodium has been developed. The carbon is oxidised in a vacuum using Van SLYKE'S solution. The carbonic acid formed is measured volumetrically; its purity can be controlled by chromatographic analysis. The results obtained show that this method makes it possible to measure carbon in concentrations of about 10 ppm. (authors) [French] Une methode de dosage par voie humide du carbone dans le sodium a ete mise au point. L'oxydation du carbone par la solution de Van SLYKE est realisee sous vide. Le gaz carbonique forme est dose volumetriquement; sa purete peut etre controlee par analyse chromatographique. Les resultats obtenus montrent que cette methode permet de doser des teneurs en carbone de l'ordre de 10 ppm. (auteurs)

Sex-biased gene expression during head development in a sexually dimorphic stalk-eyed fly.

Directory of Open Access Journals (Sweden)

Gerald S Wilkinson

Full Text Available Stalk-eyed flies (family Diopsidae are a model system for studying sexual selection due to the elongated and sexually dimorphic eye-stalks found in many species. These flies are of additional interest because their X chromosome is derived largely from an autosomal arm in other flies. To identify candidate genes required for development of dimorphic eyestalks and investigate how sex-biased expression arose on the novel X, we compared gene expression between males and females using oligonucleotide microarrays and RNA from developing eyestalk tissue or adult heads in the dimorphic diopsid, Teleopsis dalmanni. Microarray analysis revealed sex-biased expression for 26% of 3,748 genes expressed in eye-antennal imaginal discs and concordant sex-biased expression for 86 genes in adult heads. Overall, 415 female-biased and 482 male-biased genes were associated with dimorphic eyestalk development but not differential expression in the adult head. Functional analysis revealed that male-biased genes are disproportionately associated with growth and mitochondrial function while female-biased genes are associated with cell differentiation and patterning or are novel transcripts. With regard to chromosomal effects, dosage compensation occurs by elevated expression of X-linked genes in males. Genes with female-biased expression were more common on the X and less common on autosomes than expected, while male-biased genes exhibited no chromosomal pattern. Rates of protein evolution were lower for female-biased genes but higher for genes that moved on or off the novel X chromosome. These findings cannot be due to meiotic sex chromosome inactivation or by constraints associated with dosage compensation. Instead, they could be consistent with sexual conflict in which female-biased genes on the novel X act primarily to reduce eyespan in females while other genes increase eyespan in both sexes. Additional information on sex-biased gene expression in other tissues and

Biowaiver Monographs for Immediate Release Solid Oral Dosage Forms: Proguanil Hydrochloride.

NARCIS (Netherlands)

Plöger, Gerlinde F; Abrahamsson, Bertil; Cristofoletti, Rodrigo; Groot, D I R K W; Langguth, Peter; Mehta, Mehul U; Parr, Alan; Polli, James E; Shah, Vinod P; Tajiri, Tomokazu; Dressman, Jennifer B

2018-01-01

Literature data relevant to the decision to waive in vivo bioequivalence testing for the approval of generic immediate release solid oral dosage forms of proguanil hydrochloride are reviewed. To clarify the Biopharmaceutics Classification System (BCS) classification, experimental solubility and

Pharmaceutical development of an intravenous dosage form of diacetylmorphine hydrochloride

NARCIS (Netherlands)

Klous, Marjolein G.; Nuijen, Bastiaan; van den Brink, Wim; van Ree, Jan M.; Beijnen, Jos H.

2004-01-01

A solid dosage form for multiple use was developed for parenteral administration of diacetylmorphine in a clinical trial on co-prescription of heroin to heroin addicts. A 300-mg/mL diacetylmorphine hydrochloride solution was lyophilised as 10-mL aliquots in 30-mL glass vials, to be reconstituted to

Preparation, extraction and dosage of labelled cholesterol (D and C{sup 14}); Preparation, extraction et dosage de cholesterol marque (D et C{sup 14})

Energy Technology Data Exchange (ETDEWEB)

Bugnard, L; Chevallier, F; Coursaget, J [Commissariat a l' Energie Atomique, Saclay(France). Centre d' Etudes Nucleaires

1953-07-01

We returned in this note the techniques that we used for the preparation of labelled cholesterol. The chemical exchange of hydrogen enabling to contain deutero-cholesterol until 4 percent deuterium. The biologic synthesis, done on living rats or on their liver maintained in survival, permits, on the other hand, to get active cholesterol from acetate of containing sodium of the carbon 14. We indicated the techniques of extraction and dosage of the marked cholesterol. The radioactivity is measured with a Geiger-Muller counter. (M.B.) [French] Nous avons rapporte dans cette note les techniques que nous avons utilisees pour la preparation de cholesterol marque. L'echange chimique d'hydrogene conduit a du deuterio-cholesterol pouvant contenir jusqu'a 4 pour cent de deuterium. La synthese biologique, effectuee sur des rats vivants ou sur leur foie maintenu en survie, permet, d'autre part, d'obtenir du cholesterol radio-actif a partir d'acetate de sodium contenant du carbone 14. Nous avons indique les techniques d'extraction et de dosage du cholesterol marque. Sa radioactivite est mesuree au compteur de Geiger-Muller. (M.B.)

Gamma scintigraphy in the evaluation of pharmaceutical dosage forms

International Nuclear Information System (INIS)

Davis, S.S.; Hardy, J.G.; Newman, S.P.; Wilding, I.R.

1992-01-01

Gamma-scintigraphy is applied extensively in the development and evaluation of pharmaceutical drug delivery systems. It is used particularly for monitoring formulations in the gastrointestinal and respiratory tracts. The radiolabelling is generally achieved by the incorporation of an appropriate technetium-99m or indium-111 labelled radiopharmaceutical into the formulation. In the case of complex dosage forms, such as enteric-coated tablets, labelling is best undertaken by the addition of a non-radioactive tracer such as samarium-152 or erbium-170 followed by neutron activation of the final product. Systems investigated include tablets and multiparticulates for oral administration, enemas and suppositories, metered dose inhalers and nebulisers, and nasal sprays and drops. Gamma-scintigraphy provides information on the deposition, dispersion and movement of the formulation. The combination of such studies with the assay of drug levels in blood or urine specimens, pharmacoscintigraphy, provides information concerning the sites of drug release and absorption. Data acquired from the scintigraphic evaluation of pharmaceutical dosage forms are now being used increasingly at all stages of product development, from the assessment of prototype delivery systems to supporting the product licence application. (orig.)

Gamma scintigraphy in the evaluation of pharmaceutical dosage forms

Energy Technology Data Exchange (ETDEWEB)

Davis, S.S.; Hardy, J.G.; Newman, S.P.; Wilding, I.R. (Pharmaceutical Profiles Ltd., Nottingham (United Kingdom))

1992-11-01

Gamma-scintigraphy is applied extensively in the development and evaluation of pharmaceutical drug delivery systems. It is used particularly for monitoring formulations in the gastrointestinal and respiratory tracts. The radiolabelling is generally achieved by the incorporation of an appropriate technetium-99m or indium-111 labelled radiopharmaceutical into the formulation. In the case of complex dosage forms, such as enteric-coated tablets, labelling is best undertaken by the addition of a non-radioactive tracer such as samarium-152 or erbium-170 followed by neutron activation of the final product. Systems investigated include tablets and multiparticulates for oral administration, enemas and suppositories, metered dose inhalers and nebulisers, and nasal sprays and drops. Gamma-scintigraphy provides information on the deposition, dispersion and movement of the formulation. The combination of such studies with the assay of drug levels in blood or urine specimens, pharmacoscintigraphy, provides information concerning the sites of drug release and absorption. Data acquired from the scintigraphic evaluation of pharmaceutical dosage forms are now being used increasingly at all stages of product development, from the assessment of prototype delivery systems to supporting the product licence application. (orig.).

ORODISPERSIBLE TABLET: A Patient Friendly Dosage Form (a Review

Directory of Open Access Journals (Sweden)

C. K. Rameesa

2015-03-01

Full Text Available Background: The most common and preferred route of drug administration is through the oral route. Orodispersible tablets are gaining importance among novel oral drug delivery system as they have improved patient compliance and have some additional advantages compared to other formulation. They are also solid unit dosage forms, which disintegrate in the mouth within a minute in the presence of saliva due to superdisintegrants in the formulation. Thus this type of drug delivery helps a proper per oral administration in pediatric and geriatric population where swallowing is a matter of trouble. Various scientists have prepared orodispersible tablets by following various methods. However, the most common method is the direct compression method. Other special methods are Freeze Drying,Tablet Molding, Sublimation, Spray Drying, Mass extrusion, Phase transition process, etc. Since these tablets dissolve directly in the mouth, so, their taste is also an important factor. Various approaches have been taken in order to mask the bitter taste of the drug. A number of scientists have explored several drugs in this field. Like all other solid dosage forms, they are also evaluated in the field of hardness, friability, wetting time, moisture uptake, disintegration test and dissolution test.

Novel X-Linked Genes Revealed by Quantitative Polymerase Chain Reaction in the Green Anole, Anolis carolinensis

Czech Academy of Sciences Publication Activity Database

Rovatsos, M.; Altmanová, M.; Johnson Pokorná, Martina; Kratochvíl, L.

2014-01-01

Roč. 4, č. 11 (2014), s. 2107-2113 ISSN 2160-1836 R&D Projects: GA ČR GAP506/10/0718 Institutional support: RVO:67985904 Keywords : gene dosage * lizard * qPCR Subject RIV: EG - Zoology Impact factor: 3.198, year: 2014

HFE gene mutations and Wilson's disease in Sardinia.

Science.gov (United States)

Sorbello, Orazio; Sini, Margherita; Civolani, Alberto; Demelia, Luigi

2010-03-01

Hypocaeruloplasminaemia can lead to tissue iron storage in Wilson's disease and the possibility of iron overload in long-term overtreated patients should be considered. The HFE gene encodes a protein that is intimately involved in intestinal iron absorption. The aim of this study was to determine the prevalence of the HFE gene mutation, its role in iron metabolism of Wilson's disease patients and the interplay of therapy in copper and iron homeostasis. The records of 32 patients with Wilson's disease were reviewed for iron and copper indices, HFE gene mutations and liver biopsy. Twenty-six patients were negative for HFE gene mutations and did not present significant alterations of iron metabolism. The HFE mutation was significantly associated with increased hepatic iron content (PHFE gene wild-type. The HFE gene mutations may be an addictional factor in iron overload in Wilson's disease. Our results showed that an adjustment of dosage of drugs could prevent further iron overload induced by overtreatment only in patients HFE wild-type. 2009. Published by Elsevier Ltd.

Synthetic dosage lethality in the human metabolic network is highly predictive of tumor growth and cancer patient survival.

Science.gov (United States)

Megchelenbrink, Wout; Katzir, Rotem; Lu, Xiaowen; Ruppin, Eytan; Notebaart, Richard A

2015-09-29

Synthetic dosage lethality (SDL) denotes a genetic interaction between two genes whereby the underexpression of gene A combined with the overexpression of gene B is lethal. SDLs offer a promising way to kill cancer cells by inhibiting the activity of SDL partners of activated oncogenes in tumors, which are often difficult to target directly. As experimental genome-wide SDL screens are still scarce, here we introduce a network-level computational modeling framework that quantitatively predicts human SDLs in metabolism. For each enzyme pair (A, B) we systematically knock out the flux through A combined with a stepwise flux increase through B and search for pairs that reduce cellular growth more than when either enzyme is perturbed individually. The predictive signal of the emerging network of 12,000 SDLs is demonstrated in five different ways. (i) It can be successfully used to predict gene essentiality in shRNA cancer cell line screens. Moving to clinical tumors, we show that (ii) SDLs are significantly underrepresented in tumors. Furthermore, breast cancer tumors with SDLs active (iii) have smaller sizes and (iv) result in increased patient survival, indicating that activation of SDLs increases cancer vulnerability. Finally, (v) patient survival improves when multiple SDLs are present, pointing to a cumulative effect. This study lays the basis for quantitative identification of cancer SDLs in a model-based mechanistic manner. The approach presented can be used to identify SDLs in species and cell types in which "omics" data necessary for data-driven identification are missing.

The Effect of High and Low Antiepileptic Drug Dosage on Simulated Driving Performance in Person's with Seizures: A Pilot Study

Directory of Open Access Journals (Sweden)

Alexander M. Crizzle

2015-10-01

Full Text Available Background: Prior studies examining driving performance have not examined the effects of antiepileptic drugs (AED’s or their dosages in persons with epilepsy. AED’s are the primary form of treatment to control seizures, but they are shown to affect cognition, attention, and vision, all which may impair driving. The purpose of this study was to describe the characteristics of high and low AED dosages on simulated driving performance in persons with seizures. Method: Patients (N = 11; mean age 42.1 ± 6.3; 55% female; 100% Caucasian were recruited from the Epilepsy Monitoring Unit and had their driving assessed on a simulator. Results: No differences emerged in total or specific types of driving errors between high and low AED dosages. However, high AED drug dosage was significantly associated with errors of lane maintenance (r = .67, p < .05 and gap acceptance (r = .66, p < .05. The findings suggest that higher AED dosages may adversely affect driving performance, irrespective of having a diagnosis of epilepsy, conversion disorder, or other medical conditions. Conclusion: Future studies with larger samples are required to examine whether AED dosage or seizure focus alone can impair driving performance in persons with and without seizures.

In vivo evaluation of dosage forms: application of gamma scintigraphy to non-enteral routes of administration.

Science.gov (United States)

Meseguer, G; Gurny, R; Buri, P

1994-01-01

The trend to deliver drugs to defined areas of the body involves sophisticated carriers systems. In addition to the in vitro drug release profile one must be aware of the in vivo behaviour of the dosage form and the drug. Gamma scintigraphy is an elegant way to gain insights of the actual in vivo distribution pattern of dosage forms. This technique relies on the use of radioactive tracers included into the medicament and selected so as to enable an optimum detection by a gamma ray camera. The choice of a convenient label enables the in vivo determination of the targeting of the formulation administered through a large number of routes. The present paper reviews applications of gamma scintigraphy for the evaluation of dosage forms administered by the parenteral, rectal, buccal, nasal, pulmonary, and ophthalmic routes.

LABORATORY PROTECTION RATE OF TORN BEDNETS TREATED WITH THREE DOSAGES OF PYRETHROIDE AGAINST ANOPHELES CULICIFACIES

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G. Babaee

2007-05-01

Full Text Available Evaluated under laboratory condition. The objective of the present study was to observe the effect of impregnated torn bednets on the number of bites by An. culicifacies A glass made tunnel test was designed to The effect of torn bednets treated with three dosages of cyfluthrin 5% EW, were induce hungry female mosquitoes to pass through holes cut in the pyrethroid treated nets. A guinea pig used as bait to attract mosquitoes through circular holes in the netting. With untreated netting, 72-87% of laboratory-reared females passed through the holes overnight, 64-92% blood-fed successfully and 0.3/9-4/3% died. When the netting was treated with cyfluthrin at doses of 25, 50 and 100 mg a.i./m2, the entry Index (the proportions that passed through the holes overnight were 43.37%, 42.82% and 24.72%; mortality rates were 66.31%, 81.45% and 95.99%; and the feeding rate were 45%, 27% and 3%. In conclusion it should be stressed that efficacy of pyrethroid impregnated bednets using “Tunnel Tests” showing acceptable protection rate both in lower and higher dosages as well as cause dead in the blood-fed mosquitoes. In addition, the higher dosages of these three dosages pyrethroid provided good levels of protection against An. culicifacies.

Contraceptive Use Affects Overall Olfactory Performance: Investigation of Estradiol Dosage and Duration of Intake.

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Kathrin Kollndorfer

Full Text Available The influence of female sex steroids on cognitive performance and sensory perception has been investigated for decades. However, previous research that studied olfaction revealed inconsistent results. The main aim of this study was to investigate the effects of different ethinyl estradiol (EE concentrations of oral contraceptives and duration of intake on olfactory function. Forty-two healthy women, with regular intake of either high or low EE dosage over at least one year and up to 15 years participated in this study. Results revealed a significant concordance between a priori categorization in the two groups with high and low EE dosage and data-driven hierarchical clustering (p = 0.008. Furthermore, significantly higher olfactory performance was observed in women using low-dose products compared to women using high-dosed products (p = 0.019. These findings indicate different effects of pill use with regard to EE concentration. We therefore strongly recommend the acquisition of information about EE dosage of oral contraceptives to reduce potential confounding factors when investigating sensory systems.

75 FR 21162 - Certain Other Dosage Form New Animal Drugs; Detomidine

Science.gov (United States)

2010-04-23

.... FDA-2010-N-0002] Certain Other Dosage Form New Animal Drugs; Detomidine AGENCY: Food and Drug... NADA provides for veterinary prescription use of detomidine hydrochloride oromucosal gel for sedation... prescription use of DORMOSEDAN GEL (detomidine hydrochloride) for sedation and restraint of horses. The...

Arsenic removal from groundwater using iron electrocoagulation: effect of charge dosage rate.

Science.gov (United States)

Amrose, Susan; Gadgil, Ashok; Srinivasan, Venkat; Kowolik, Kristin; Muller, Marc; Huang, Jessica; Kostecki, Robert

2013-01-01

We demonstrate that electrocoagulation (EC) using iron electrodes can reduce arsenic below 10 μg/L in synthetic Bangladesh groundwater and in real groundwater from Bangladesh and Cambodia, while investigating the effect of operating parameters that are often overlooked, such as charge dosage rate. We measure arsenic removal performance over a larger range of current density than in any other single previous EC study (5000-fold: 0.02 - 100 mA/cm(2)) and over a wide range of charge dosage rates (0.060 - 18 Coulombs/L/min). We find that charge dosage rate has significant effects on both removal capacity (μg-As removed/Coulomb) and treatment time and is the appropriate parameter to maintain performance when scaling to different active areas and volumes. We estimate the operating costs of EC treatment in Bangladesh groundwater to be $0.22/m(3). Waste sludge (~80 - 120 mg/L), when tested with the Toxic Characteristic Leachate Protocol (TCLP), is characterized as non-hazardous. Although our focus is on developing a practical device, our results suggest that As[III] is mostly oxidized via a chemical pathway and does not rely on processes occurring at the anode. Supplementary materials are available for this article. Go to the publisher's online edition of Journal of Environmental Science and Health, Part A, to view the free supplemental file.

Chromosomal Arrangement of Phosphorelay Genes Couples Sporulation and DNA Replication.

Science.gov (United States)

Narula, Jatin; Kuchina, Anna; Lee, Dong-Yeon D; Fujita, Masaya; Süel, Gürol M; Igoshin, Oleg A

2015-07-16

Genes encoding proteins in a common regulatory network are frequently located close to one another on the chromosome to facilitate co-regulation or couple gene expression to growth rate. Contrasting with these observations, here, we demonstrate a functional role for the arrangement of Bacillus subtilis sporulation network genes on opposite sides of the chromosome. We show that the arrangement of two sporulation network genes, one located close to the origin and the other close to the terminus, leads to a transient gene dosage imbalance during chromosome replication. This imbalance is detected by the sporulation network to produce cell-cycle coordinated pulses of the sporulation master regulator Spo0A∼P. This pulsed response allows cells to decide between sporulation and continued vegetative growth during each cell cycle spent in starvation. The simplicity of this coordination mechanism suggests that it may be widely applicable in a variety of gene regulatory and stress-response settings. VIDEO ABSTRACT. Copyright © 2015 Elsevier Inc. All rights reserved.

The accuracy of warfarin dosage based on VKORC1 and CYP2C9 phenotypes in a Chinese population

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Agustinus Wijaya

2012-05-01

Full Text Available Background: The aim of this study is to assess the accuracy of warfarin dosage based on VKORC1 and CYP2C9 genotype in Chinese population.Methods: Blood samples were taken from 37 patients. We compared the warfarin dosage obtained from genotype (according to www.warfarindosing.org and treatment dosage with international normalized ratio (INR value within 2.0-3.0.Results: The majority of Chinese people in our study are VKORC1 homozygous AA (89.2%, rarely VKORC1 heterozygous AG and we cannot find a patient with homozygous GG. For CYP2C9 genotype, most patients have the wildtype variants (CYP2C9*2 CC and CYP2C9*3 AA. The warfarin dosage for patients with VKORC1 AA and CYP2C9*3 AC is lower than for patients with other genotype variants.Conclusion: There is no significant difference between pharmacogenetic algorithm (www.warfarindosing.org and our treatment dosage. Our conclusion is that the pharmacogenetic algorithm is accurate to predict the warfarin dose. (Med J Indones. 2012;21:108-12Keywords: CYP2C9, pharmacogenetic algorithm, VKORC1, warfarin

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

Science.gov (United States)

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

2013-02-01

Literature data pertaining to the decision to allow a waiver of in vivo bioequivalence testing for the approval of immediate-release (IR) solid oral dosage forms containing efavirenz as the only active pharmaceutical ingredient (API) are reviewed. Because of lack of conclusive data about efavirenz's permeability and its failure to comply with the "high solubility" criteria according to the Biopharmaceutics Classification System (BCS), the API can be classified as BCS Class II/IV. In line with the solubility characteristics, the innovator product does not meet the dissolution criteria for a "rapidly dissolving product." Furthermore, product variations containing commonly used excipients or in the manufacturing process have been reported to impact the rate and extent of efavirenz absorption. Despite its wide therapeutic index, subtherapeutic levels of efavirenz can lead to treatment failure and also facilitate the emergence of efavirenz-resistant mutants. For all these reasons, a biowaiver for IR solid oral dosage forms containing efavirenz as the sole API is not scientifically justified for reformulated or multisource drug products. Copyright © 2012 Wiley Periodicals, Inc.

Laūq: A Sustained-Release Dosage Form for Respiratory Disorders in Traditional Persian Medicine.

Science.gov (United States)

Karegar-Borzi, Hossein; Salehi, Mehdi; Rahimi, Roja

2016-01-01

Laūq is a pharmaceutical dosage form that had been mainly used for the treatment of various respiratory disorders in traditional Persian medicine. It is important from 2 aspects: a dosage form with efficient and optimum delivery of drugs to the respiratory tract and biological effects of its ingredients. Natural medicine in laūq has been demonstrated to act in respiratory disorders by their antitussive, antiallergic, anti-inflammatory, antioxidant, spasmolytic, and antibacterial activities. Some of these natural remedies act by most of the mentioned mechanisms such as Cydonia oblonga, Glycyrrhiza glabra, Crocus sativus, Hyssopus officinalis, Foeniculum vulgare, and honey. However, the evidence is limited including Cassia fistula, Papaver somniferum, and Drimia maritima. According to positive pharmacokinetic and pharmacodynamic aspects of laūqs, they may be considered as efficient dosage forms for delivery of drugs to the respiratory tract. For better compatibility of patients, it could be substituted laūqs with newer drug delivery systems like lozenges. © The Author(s) 2015.

Differential retention of metabolic genes following whole-genome duplication.

Science.gov (United States)

Gout, Jean-François; Duret, Laurent; Kahn, Daniel

2009-05-01

Classical studies in Metabolic Control Theory have shown that metabolic fluxes usually exhibit little sensitivity to changes in individual enzyme activity, yet remain sensitive to global changes of all enzymes in a pathway. Therefore, little selective pressure is expected on the dosage or expression of individual metabolic genes, yet entire pathways should still be constrained. However, a direct estimate of this selective pressure had not been evaluated. Whole-genome duplications (WGDs) offer a good opportunity to address this question by analyzing the fates of metabolic genes during the massive gene losses that follow. Here, we take advantage of the successive rounds of WGD that occurred in the Paramecium lineage. We show that metabolic genes exhibit different gene retention patterns than nonmetabolic genes. Contrary to what was expected for individual genes, metabolic genes appeared more retained than other genes after the recent WGD, which was best explained by selection for gene expression operating on entire pathways. Metabolic genes also tend to be less retained when present at high copy number before WGD, contrary to other genes that show a positive correlation between gene retention and preduplication copy number. This is rationalized on the basis of the classical concave relationship relating metabolic fluxes with enzyme expression.

Quantitative analysis of the dystrophin gene by real-time PCR

Directory of Open Access Journals (Sweden)

Maksimovic Nela

2012-01-01

Full Text Available Duchenne and Becker muscular dystrophy (DMD/BMD are severe X-linked neuromuscular disorders caused by mutations in the dystrophin gene. Our aim was to optimize a quantitative real-time PCR method based on SYBR® Green I chemistry for routine diagnostics of DMD/BMD deletion carriers. Twenty female relatives of DMD/BMD patients with previously detected partial gene deletions were studied. The relative quantity of the target exons was calculated by a comparative threshold cycle method (ΔΔCt. The carrier status of all subjects was successfully determined. The gene dosage ratio for non-carriers was 1.07±0.20, and for carriers 0.56±0.11. This assay proved to be simple, rapid, reliable and cost-effective.

78 FR 30197 - Oral Dosage Form New Animal Drugs; Clindamycin; Enrofloxacin

Science.gov (United States)

2013-05-22

...-0002] Oral Dosage Form New Animal Drugs; Clindamycin; Enrofloxacin AGENCY: Food and Drug Administration...- Tallaght, Dublin Oral Drops. 940. 24, Ireland. 200-551........ Putney, Inc., 400 Enrofloxacin Original....812 Enrofloxacin. (a) Specifications. Each tablet contains 22.7, 68.0, or 136.0 milligrams (mg) of...

Effect of lead acetate administered orally at different dosage levels ...

African Journals Online (AJOL)

The project was conducted to evaluate the effect of lead administered as lead acetate at different dosage levels via drinking water in broiler chicks. Thirty-five healthy chicks were divided into seven groups (five chicks each) and one group was kept as un-medicated control. Groups A, B, C, D, E and F were medicated with ...

When and how should we teach the basic concepts of radiation beam dosage

International Nuclear Information System (INIS)

Brewin, T.B.

1977-01-01

The difficulty that many trainees, including those medically qualified, have in achieving a sound working grasp of certain basic principles of radiation beam dosage is often underestimated. Since any failure of understanding may seriously impair the efficiency of the team treating the patient, the discussion of these problems (and especially the monitoring of the results of such discussion by means of oral and written tests) deserves a high priority. Contrary to traditional practice, there would seem to be no good reason why teaching of radiation beam dosage, and the effect on dose-rate of changes in the treatment distance or in the amount of scattered radiation, should not begin in the very first week of training and be immediately integrated with discussion of the dose-rate information available at every radiotherapy unit when the patient is treated. A preliminary course of physics lectures does not usually make the understanding of these principles any easier and can be done either concurrently or later. For many radiotherapy trainees and for many doctors in other fields, comparison with drug dosage and with the brightness and scatter of ordinary light beams, avoiding technical terms so far as possible, may achieve a better initial understanding of basic principles than is achieved by mathematical equations and theoretical physics. (author)

When and how should we teach the basic concepts of radiation beam dosage

Energy Technology Data Exchange (ETDEWEB)

Brewin, T B [Institute of Radiotherapeutics and Oncology, Glasgow (UK)

1977-06-01

The difficulty that many trainees, including those medically qualified, have in achieving a sound working grasp of certain basic principles of radiation beam dosage is often underestimated. Since any failure of understanding may seriously impair the efficiency of the team treating the patient, the discussion of these problems (and especially the monitoring of the results of such discussion by means of oral and written tests) deserves a high priority. Contrary to traditional practice, there would seem to be no good reason why teaching of radiation beam dosage, and the effect on dose-rate of changes in the treatment distance or in the amount of scattered radiation, should not begin in the very first week of training and be immediately integrated with discussion of the dose-rate information available at every radiotherapy unit when the patient is treated. A preliminary course of physics lectures does not usually make the understanding of these principles any easier and can be done either concurrently or later. For many radiotherapy trainees and for many doctors in other fields, comparison with drug dosage and with the brightness and scatter of ordinary light beams, avoiding technical terms so far as possible, may achieve a better initial understanding of basic principles than is achieved by mathematical equations and theoretical physics.

Population and sex differences in Drosophila melanogaster brain gene expression

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Catalán Ana

2012-11-01

Full Text Available Abstract Background Changes in gene regulation are thought to be crucial for the adaptation of organisms to their environment. Transcriptome analyses can be used to identify candidate genes for ecological adaptation, but can be complicated by variation in gene expression between tissues, sexes, or individuals. Here we use high-throughput RNA sequencing of a single Drosophila melanogaster tissue to detect brain-specific differences in gene expression between the sexes and between two populations, one from the ancestral species range in sub-Saharan Africa and one from the recently colonized species range in Europe. Results Relatively few genes (Cyp6g1 and CHKov1. Conclusions Analysis of the brain transcriptome revealed many genes differing in expression between populations that were not detected in previous studies using whole flies. There was little evidence for sex-specific regulatory adaptation in the brain, as most expression differences between populations were observed in both males and females. The enrichment of genes with sexually dimorphic expression on the X chromosome is consistent with dosage compensation mechanisms affecting sex-biased expression in somatic tissues.

Meta-analysis : High-dosage vitamin E supplementation may increase all-cause mortality

NARCIS (Netherlands)

Miller, ER; Pastor-Barriuso, R; Dalal, D; Riemersma, RA; Appel, LJ; Guallar, E

2005-01-01

Background: Experimental models and observational studies suggest that vitamin E supplementation may prevent cardiovascular disease and cancer. However, several trials of high-dosage vitamin E supplementation showed non-statistically significant increases in total mortality. Purpose: To perform a

New applications to computerized tomography: analysis of solid dosage forms produced by pharmaceutical industry

International Nuclear Information System (INIS)

Oliveira Junior, Jose Martins de; Martins, Antonio Cesar Germano

2009-01-01

Full text: In recent years, computerized tomography (CT) has been used as a new probe to study solid dosage forms (tablets) produced by pharmaceutical industry. This new approach to study tablet and powder, or granulation, properties used in pharmaceutical industry is very suitable. First because CT can generate information that traditional technologies used in this kind of analysis can not, such as, density distribution of internal structures and tablet dimensions, pore size distribution, particle shape information, and also investigation of official and unofficial (counterfeit) copies of solid dosage forms. Second because CT is a nondestructive technique, allowing the use of tablets or granules in others analysis. In this work we discus how CT can be used to acquire and reconstruct internal microstructure of tablets and granules. CT is a technique that is based on attenuation of X-rays passing through matter. Attenuation depends on the density and atomic number of the material that is scanned. In this work, a micro-CT X-ray scanner (manufactured by the group of Applied Nuclear Physics at University of Sorocaba) was used to obtain three-dimensional images of the tablets and granules for nondestructive analysis. These images showed a non uniform density distribution of material inside some tablets, the morphology of some granules analyzed, the integrity of the liquid-filled soft-gelatin capsule and so on. It could also be observed that the distribution of different constituents presents an osmotic controlled-release dosage form. The present work shows that it is possible to use X-ray microtomography to obtain useful qualitative and quantitative information on the structure of pharmaceutical dosage forms. (author)

THE INFLUENCE OF CALCIUM HYPOCHLORITE DOSAGE ADJUSTMENT ON TAPIOCA WASTEWATER PRE-CHLORINATION TOWARD EFFICIENCY OF ACTIVATED SLUDGE TREATMENT

Directory of Open Access Journals (Sweden)

Happy Mulyani

2016-11-01

Full Text Available The objectives of this research are to study about influence of calcium hypochlorite dosage adjustment on tapioca wastewater chlorination toward efficiency of activated sludge treatment especially at MLVSS profile and percentage of COD removal. This research mainly divided into pre-chlorination and activated sludge treatment. Pre-chlorination taken place for 60 minutes at pH 8. The variation of calcium hypochlorite dosages which used are 58, 59, and 60 mg/L. Pre-chlorination effluent with no free chlorine residual then becomes activated sludge treatment influent. Sampling has done each aeration time interval 0, 2, 4, and 6 hour for analysis of COD and MLVSS content. Research result generally shows that addition of aeration time for each variation of calcium hypochlorite dosage will increase MLVSS and decrease COD content. Smallest value of COD effluent could achieved in the activated sludge treatment with calcium hipochlorite dosage 60 mg/L addition at influent during 4 hours aeration time. Addition of 58 mg/l calcium hypochlorite results highest MLVSS and percentage of COD removal.

Clinical efficacy of dexmedetomidine in the diminution of fentanyl dosage in pediatric cardiac surgery.

Science.gov (United States)

Sun, Yingying; Ye, Hongwu; Xia, Yin; Li, Yuanhai; Yuan, Xianren; Wang, Xing

2017-06-01

This study aims to explore the clinical efficacy of dexmedetomidine (DEX) in the diminution of fentanyl dosage in pediatric cardiac surgery based on some clinical and biochemical parameters. Fifty pediatric patients (American Society of Anesthesiologists II), 1-6 years old, were randomly allocated into two groups: group F (control group), in which patients received normal saline and high dosage of fentanyl (30 μg/kg), and group D, in which patients were given DEX and low dosage of fentanyl (15 μg/kg). Some hemodynamic and clinical parameters of the two groups were recorded. Furthermore, stress hormone (serum cortisol, norepinephrine, blood glucose) levels and cytokine (interleukin 6, tumor necrosis factor alpha) levels in the two groups were compared with each other. Stress hormone levels, cytokine levels, hemodynamic parameters and the consumption of sevoflurane did not differ between the two groups. Meanwhile, the extubation time was significantly shorter in Group D than F (Pfentanyl supplemented with DEX almost had the same anesthesia effects and inflammation extent compared with high dose of fentanyl, which suggested that infusion DEX might decrease fentanyl consumption in pediatric cardiac surgery.

Neurodevelopmental disorders associated with dosage imbalance of ZBTB20 correlate with the morbidity spectrum of ZBTB20 candidate target genes

DEFF Research Database (Denmark)

Rasmussen, Malene B; Nielsen, Jakob V; Lourenço, Charles M

2014-01-01

(SRO) involved five RefSeq genes, including the transcription factor gene ZBTB20 and the dopamine receptor gene DRD3, considered as candidate genes for the syndrome. METHODS AND RESULTS: We used array comparative genomic hybridization and next-generation mate-pair sequencing to identify key structural...... patient with developmental delay and autism, we detected the first microdeletion at 3q13.31, which truncated ZBTB20 but did not involve DRD3 or the other genes within the previously defined SRO. Zbtb20 directly represses 346 genes in the developing murine brain. Of the 342 human orthologous ZBTB20...

Oxytocin efficacy is modulated by dosage and oxytocin receptor genotype in young adults with high-functioning autism: a 24-week randomized clinical trial.

Science.gov (United States)

Kosaka, H; Okamoto, Y; Munesue, T; Yamasue, H; Inohara, K; Fujioka, T; Anme, T; Orisaka, M; Ishitobi, M; Jung, M; Fujisawa, T X; Tanaka, S; Arai, S; Asano, M; Saito, D N; Sadato, N; Tomoda, A; Omori, M; Sato, M; Okazawa, H; Higashida, H; Wada, Y

2016-08-23

Recent studies have suggested that long-term oxytocin administration can alleviate the symptoms of autism spectrum disorder (ASD); however, factors influencing its efficacy are still unclear. We conducted a single-center phase 2, pilot, randomized, double-blind, placebo-controlled, parallel-group, clinical trial in young adults with high-functioning ASD, to determine whether oxytocin dosage and genetic background of the oxytocin receptor affects oxytocin efficacy. This trial consisted of double-blind (12 weeks), open-label (12 weeks) and follow-up phases (8 weeks). To examine dose dependency, 60 participants were randomly assigned to high-dose (32 IU per day) or low-dose intranasal oxytocin (16 IU per day), or placebo groups during the double-blind phase. Next, we measured single-nucleotide polymorphisms (SNPs) in the oxytocin receptor gene (OXTR). In the intention-to-treat population, no outcomes were improved after oxytocin administration. However, in male participants, Clinical Global Impression-Improvement (CGI-I) scores in the high-dose group, but not the low-dose group, were significantly higher than in the placebo group. Furthermore, we examined whether oxytocin efficacy, reflected in the CGI-I scores, is influenced by estimated daily dosage and OXTR polymorphisms in male participants. We found that >21 IU per day oxytocin was more effective than ⩽21 IU per day, and that a SNP in OXTR (rs6791619) predicted CGI-I scores for ⩽21 IU per day oxytocin treatment. No severe adverse events occurred. These results suggest that efficacy of long-term oxytocin administration in young men with high-functioning ASD depends on the oxytocin dosage and genetic background of the oxytocin receptor, which contributes to the effectiveness of oxytocin treatment of ASD.

A De Novo Whole GCK Gene Deletion Not Detected by Gene Sequencing, in a Boy with Phenotypic GCK Insufficiency

Directory of Open Access Journals (Sweden)

N. H. Birkebæk

2011-01-01

Full Text Available We report on a boy with diabetes mellitus and a phenotype indicating glucokinase (GCK insufficiency, but a normal GCK gene examination applying direct gene sequencing. The boy was referred for diabetes mellitus at 7.5 years old. His father, grandfather and great grandfather suffered type 2 DM. Several blood glucose profiles showed (BG of 6.5–10 mmol/L L. After three years on neutral insulin Hagedorn (NPH in a dose of 0.3 IU/kg/day haemoglobin A1c (HbA1c was 6.8%. Treatment was changed to sulphonylurea 750 mg a day, and after 4 years HbA1c was 7%. At that time a multiplex ligation-dependent amplification gene dosage assay (MLPA was done, revealing a whole GCK gene deletion. Medical treatment was ceased, and after one year HbA1c was 6.8%. This case underscores the importance of a MLPA examination if the phenotype of a patient is strongly indicative of GCK insufficiency and no mutation is identified using direct sequencing.

Effects of starch synthase IIa gene dosage on grain, protein and starch in endosperm of wheat.

Science.gov (United States)

Konik-Rose, Christine; Thistleton, Jenny; Chanvrier, Helene; Tan, Ihwa; Halley, Peter; Gidley, Michael; Kosar-Hashemi, Behjat; Wang, Hong; Larroque, Oscar; Ikea, Joseph; McMaugh, Steve; Regina, Ahmed; Rahman, Sadequr; Morell, Matthew; Li, Zhongyi

2007-11-01

Starch synthases (SS) are responsible for elongating the alpha-1,4 glucan chains of starch. A doubled haploid population was generated by crossing a line of wheat, which lacks functional ssIIa genes on each genome (abd), and an Australian wheat cultivar, Sunco, with wild type ssIIa alleles on each genome (ABD). Evidence has been presented previously indicating that the SGP-1 (starch granule protein-1) proteins present in the starch granule in wheat are products of the ssIIa genes. Analysis of 100 progeny lines demonstrated co-segregation of the ssIIa alleles from the three genomes with the SGP-1 proteins, providing further evidence that the SGP-1 proteins are the products of the ssIIa genes. From the progeny lines, 40 doubled haploid lines representing the eight possible genotypes for SSIIa (ABD, aBD, AbD, ABd, abD, aBd, Abd, abd) were characterized for their grain weight, protein content, total starch content and starch properties. For some properties (chain length distribution, pasting properties, swelling power, and gelatinization properties), a progressive change was observed across the four classes of genotypes (wild type, single nulls, double nulls and triple nulls). However, for other grain properties (seed weight and protein content) and starch properties (total starch content, granule morphology and crystallinity, granule size distribution, amylose content, amylose-lipid dissociation properties), a statistically significant change only occurred for the triple nulls, indicating that all three genes had to be missing or inactive for a change to occur. These results illustrate the importance of SSIIa in controlling grain and starch properties and the importance of amylopectin fine structure in controlling starch granule properties in wheat.

A duplicated PLP gene causing Pelizaeus-Merzbacher disease detected by comparative multiplex PCR

Energy Technology Data Exchange (ETDEWEB)

Inoue, K.; Sugiyama, N.; Kawanishi, C. [Yokohama City Univ., Yokohama (Japan)] [and others

1996-07-01

Pelizaeus-Merzbacher disease (PMD) is an X-linked dysmyelinating disorder caused by abnormalities in the proteolipid protein (PLP) gene, which is essential for oligodendrocyte differentiation and CNS myelin formation. Although linkage analysis has shown the homogeneity at the PLP locus in patients with PMD, exonic mutations in the PLP gene have been identified in only 10% - 25% of all cases, which suggests the presence of other genetic aberrations, including gene duplication. In this study, we examined five families with PMD not carrying exonic mutations in PLP gene, using comparative multiplex PCR (CM-PCR) as a semiquantitative assay of gene dosage. PLP gene duplications were identified in four families by CM-PCR and confirmed in three families by densitometric RFLP analysis. Because a homologous myelin protein gene, PMP22, is duplicated in the majority of patients with Charcot-Marie-Tooth 1A, PLP gene overdosage may be an important genetic abnormality in PMD and affect myelin formation. 38 ref., 5 figs., 2 tabs.

Discrete element method (DEM) simulations of stratified sampling during solid dosage form manufacturing.

Science.gov (United States)

Hancock, Bruno C; Ketterhagen, William R

2011-10-14

Discrete element model (DEM) simulations of the discharge of powders from hoppers under gravity were analyzed to provide estimates of dosage form content uniformity during the manufacture of solid dosage forms (tablets and capsules). For a system that exhibits moderate segregation the effects of sample size, number, and location within the batch were determined. The various sampling approaches were compared to current best-practices for sampling described in the Product Quality Research Institute (PQRI) Blend Uniformity Working Group (BUWG) guidelines. Sampling uniformly across the discharge process gave the most accurate results with respect to identifying segregation trends. Sigmoidal sampling (as recommended in the PQRI BUWG guidelines) tended to overestimate potential segregation issues, whereas truncated sampling (common in industrial practice) tended to underestimate them. The size of the sample had a major effect on the absolute potency RSD. The number of sampling locations (10 vs. 20) had very little effect on the trends in the data, and the number of samples analyzed at each location (1 vs. 3 vs. 7) had only a small effect for the sampling conditions examined. The results of this work provide greater understanding of the effect of different sampling approaches on the measured content uniformity of real dosage forms, and can help to guide the choice of appropriate sampling protocols. Copyright © 2011 Elsevier B.V. All rights reserved.

Onabotulinum toxin A dosage trends over time for adductor spasmodic dysphonia: A 15-year experience.

Science.gov (United States)

Tang, Christopher G; Novakovic, Daniel; Mor, Niv; Blitzer, Andrew

2016-03-01

Although onabotulinum neurotoxin A (BoNTA) has been used for over three decades for the treatment of adductor spasmodic dysphonia, no study has been performed to look at the trend of BoNTA dosages across time. The goal of this study is to evaluate the dosage trends to determine if the dosage necessary for voice improvement in patients increases over time. Charts were reviewed for patients with 15 years or more of experience. Linear regression analysis was performed to determine correlation coefficients and trends. Fifty-five patients receiving BoNTA injections by the senior author (a.b.) for over 15 years were evaluated. Thirty-nine patients (82% female) met inclusion criteria. Patients received injections over an average of 18.6 years ± 1.36 years, with the longest follow-up of 21.5 years. Of 39 patients, 16 (41%) had a negative correlation coefficient (Pearson's r) suggesting a decrease over time, whereas 23 (59%) had a positive correlation coefficient suggesting an increase over time. The mean correlation coefficient was 0.139 ± 0.534 and P  0.05 in 20 patients. R(2) for all patients were less than 0.75. Onabotulinum neurotoxin A injection dosage trends vary depending on the individual over time. Overall, the dose range appears to be stable in the majority of patients, suggesting that tolerance does not play a significant part in dose variation over time. 4. Laryngoscope, 126:678-681, 2016. © 2015 The American Laryngological, Rhinological and Otological Society, Inc.

Application of DBNPA dosage for biofouling control in spiral wound membrane systems

KAUST Repository

Siddiqui, Amber; Pinel, I.; Prest, E.I.; Bucs, Szilard; van Loosdrecht, M.C.M.; Kruithof, J.C.; Vrouwenvelder, Johannes S.

2017-01-01

in MFS was quantified by adenosine triphosphate (ATP) and total organic carbon (TOC) analysis. Continuous dosage of DBNPA (1 mg/L) prevented pressure drop increase and biofilm accumulation in the MFSs during a run time of 7 d, showing that biofouling can

A multicenter study of the effect of dietary supplementation with fish oil omega-3 fatty acids on carprofen dosage in dogs with osteoarthritis.

Science.gov (United States)

Fritsch, Dale A; Allen, Timothy A; Dodd, Chadwick E; Jewell, Dennis E; Sixby, Kristin A; Leventhal, Phillip S; Brejda, John; Hahn, Kevin A

2010-03-01

To determine the effects of feeding a diet supplemented with fish oil omega-3 fatty acids on carprofen dosage in dogs with osteoarthritis. Randomized, controlled, multisite clinical trial. 131 client-owned dogs with stable chronic osteoarthritis examined at 33 privately owned veterinary hospitals in the United States. In all dogs, the dosage of carprofen was standardized over a 3-week period to approximately 4.4 mg/kg/d (2 mg/lb/d), PO. Dogs were then randomly assigned to receive a food supplemented with fish oil omega-3 fatty acids or a control food with low omega-3 fatty acid content, and 3, 6, 9, and 12 weeks later, investigators made decisions regarding increasing or decreasing the carprofen dosage on the basis of investigator assessments of 5 clinical signs and owner assessments of 15 signs. Linear regression analysis indicated that over the 12-week study period, carprofen dosage decreased significantly faster among dogs fed the supplemented diet than among dogs fed the control diet. The distribution of changes in carprofen dosage for dogs in the control group was significantly different from the distribution of changes in carprofen dosage for dogs in the test group. Results suggested that in dogs with chronic osteoarthritis receiving carprofen because of signs of pain, feeding a diet supplemented with fish oil omega-3 fatty acids may allow for a reduction in carprofen dosage.

Derivative spectrophotometric method for simultaneous determination of clindamycin phosphate and tretinoin in pharmaceutical dosage forms.

Science.gov (United States)

Barazandeh Tehrani, Maliheh; Namadchian, Melika; Fadaye Vatan, Sedigheh; Souri, Effat

2013-04-10

A derivative spectrophotometric method was proposed for the simultaneous determination of clindamycin and tretinoin in pharmaceutical dosage forms. The measurement was achieved using the first and second derivative signals of clindamycin at (1D) 251 nm and (2D) 239 nm and tretinoin at (1D) 364 nm and (2D) 387 nm.The proposed method showed excellent linearity at both first and second derivative order in the range of 60-1200 and 1.25-25 μg/ml for clindamycin phosphate and tretinoin respectively. The within-day and between-day precision and accuracy was in acceptable range (CVpharmaceutical dosage form.

Intra-individual comparison of PET/CT with different body weight-adapted FDG dosage regimens

International Nuclear Information System (INIS)

Geismar, Jan H; Stolzmann, Paul; Sah, Bert-Ram; Burger, Irene A; Seifert, Burkhardt; Delso, Gaspar; Schulthess, Gustav K von; Veit-Haibach, Patrick; Husmann, Lars

2015-01-01

18F-2-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET)/ computed tomography (CT) imaging demands guidelines to safeguard sufficient image quality at low radiation exposure. Various FDG dose regimes have been investigated; however, body weight-adapted dose regimens and related image quality (IQ) have not yet been compared in the same patient. To investigate the relationship between FDG dosage and image quality in PET/CT in the same patient and determine prerequisites for low dosage scanning. This study included 61 patients undergoing a clinically indicated PET/CT imaging study and follow-up with a normal (NDS, 5 MBq/kg body weight [BW]) and low dosage scanning protocol (LDS, 4 MBq/kg BW), respectively, using a Discovery VCT64 scanner. Two blinded and independent readers randomly assessed IQ of PET using a 5-point Likert scale and signal-to-noise ratio (SNR) of the liver. Body mass index (BMI) was significantly lower at LDS (P = 0.021) and represented a significant predictor of SNR at both NDS (P < 0.001) and LDS (P = 0.005). NDS with a mean administered activity of 340 MBq resulted in significantly higher IQ (P < 0.001) and SNR as compared with LDS with a mean of 264 MBq (F-value = 23.5, P < 0.001, mixed model ANOVA adjusted for covariate BMI). Non-diagnostic IQ at LDS was associated with a BMI > 22 kg/m 2 . FDG dosage significantly predicts IQ and SNR in PET/CT imaging as demonstrated in the same patient with optimal IQ achieved at 5 MBq/kg BM. PET/CT imaging at 4 MBq/kg BW may only be recommended in patients with a BMI ≤ 22 kg/m 2 to maintain diagnostic IQ

[Oral films as perspective dosage form].

Science.gov (United States)

Walicová, Veronika; Gajdziok, Jan

Oral films, namely buccal mucoadhesive films and orodispersible films represent innovative formulations for administration of a wide range of drugs. Oral films show many advantageous properties and are intended for systemic drug delivery or for local treatment of the oral mucosa. In both cases, the film represents a thin layer, which could be intended to adhere to the oral mucosa by means of mucoadhesion; or to rapid dissolution and subsequent swallowing without the need of liquid intake, in the case of orodispersible films. Main constitutive excipients are film-forming polymers, which must in the case of mucoadhesive forms remain on the mucosa within the required time interval. Oral films are currently available on the pharmaceutical market and could compete with conventional oral dosage forms in the future. oral cavity oral films buccal mucoadhesive films orodispersible films film-forming polymers.

Standardization of radioimmunoassay for dosage of angiotensin II (ang-II) and its methodological evaluation

International Nuclear Information System (INIS)

Mantovani, Milene; Mecawi, Andre S.; Elias, Lucila L.K.; Antunes-Rodrigues, Jose

2011-01-01

This paper standardizes the radioimmunoassay (RIA) for dosage of ANG-II of rats, after experimental conditions of saline hypertonic (2%), treating with losartan (antagonist of ANG-II), hydric privation, and acute hemorrhage (25%). After that, the plasmatic ANG-II was extracted for dosage of RIA, whose sensitiveness was of 1.95 pg/m L, with detection of 1.95 to 1000 pg/m L. The treatment with saline reduced the concentration of ANG-II, while the administration pf losartan, the hydric administration and the hemorrhage increase the values, related to the control group. Those results indicate variations in the plasmatic concentration of ANG-II according to the experimental protocols, validating the method for evaluation of activity renin-angiotensin

Patient perception of methadone dose adequacy in methadone maintenance treatment: The role of perceived participation in dosage decisions.

Science.gov (United States)

Trujols, Joan; González-Saiz, Francisco; Manresa, María José; Alcaraz, Saul; Batlle, Francesca; Duran-Sindreu, Santiago; Pérez de Los Cobos, José

2017-05-01

In clinical practice, methadone maintenance treatment (MMT) entails tailoring the methadone dose to the patient's specific needs, thereby individualizing treatment. The aim of this study was to identify the independent factors that may significantly explain methadone dose adequacy from the patient's perspective. Secondary analysis of data collected in a treatment satisfaction survey carried out among a representative sample of MMT patients (n=122) from the region of La Rioja (Spain). As part of the original study protocol, participants completed a comprehensive battery to assess satisfaction with MMT, psychological distress, opinion of methadone as a medication, participation in dosage decisions, and perception of dose adequacy. Multivariate binary logistic regression showed that the only variable independently associated with the likelihood of a patient perceiving methadone dose as inadequate was the variable perceived-participation in methadone dosage decisions (OR=0.538, 95% CI=0.349-0.828). Patient participation in methadone dosage decisions was predictive of perceived adequacy of methadone dose beyond the contribution of other socio-demographic, clinical, and MMT variables. Patient participation in methadone dosage decision-making is valuable for developing a genuinely patient-centred MMT. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

76 FR 16533 - Certain Other Dosage Form New Animal Drugs; Detomidine; Correction

Science.gov (United States)

2011-03-24

.... FDA-2010-N-0002] Certain Other Dosage Form New Animal Drugs; Detomidine; Correction AGENCY: Food and... paragraph describing limitations to the approved conditions of use for detomidine hydrochloride oromucosal... conditions of use for detomidine hydrochloride oromucosal gel in horses. This correction is being made to...

The influence of Aspergillus niger inoculum dosage on nutritive value and metabolizable energy of apu-apu meal (Pistia stratiotes L.) on broiler chicken

Science.gov (United States)

Gloria, J.; Tafsin, M.; Hanafi, N. D.; Daulay, A. H.

2018-02-01

Apu-apu lives at tropical and subtropical fresh waterways. The apu-apu meals ultization as feed still limited. The problem of ultization apu-apu meals as ingredients is a high crude fiber and need a treatment to decrease crude fiber. This study aim to find out the influence of Aspergillus niger inoculums dosage on apu-apu meal (Pistia stratiotes L.) on metabolizable energy on broiler chicken. This research used completely randomize design (CRD). The treatments consists of Aspergillus niger inoculum dosage (CFU/g) such as P0 (0), P1 (104 CFU/g), P2 (106 CFU/g), and P3 (108 CFU/g). The variable were observed : apparent metabolizable energy (AME), true metabolizable energy (TME), apparent metabolizable energy nitrogen corrected (AMEn) and true metabolizable energy nitrogen corrected (TMEn).The results showed that the dosage of Aspergillus niger increase nutritive value of Aspergillus niger. Dosage of Aspergillus niger also influence (P<0.05) metabolizable energy of apu-apu meals. Dosage 108 CFU/g had metabolizable energy significantly higher than other treatments. Conclusion of this research is the Aspergillus niger at the dosage 108 CFU/g increased nutritive value and metabolizable energy of apu-apu meal.

Dependence of 'CT clearance' on dosage and time

International Nuclear Information System (INIS)

Kaltenborn, H.A.; Klose, K.J.; Dexheimer, C.; Steinijans, V.

1989-01-01

The contrast medium dose used in CT renal function analysis corresponds to about 1 ml/kg body weight at a measurement interval of 5 or 10 minutes. In the present study the dependence of 'CT clearance' on dosage and time was examined in 12 healthy subjects. The amount of clearance was directly proportional to the employed contrast medium dose and to the length of the measurement interval. On account of the superior signal-to-noise ratio, the higher dose (1 ml/kg body weight) will continue to be prefered in future. The measurement interval can be limited to 10 minutes. (orig.) [de

Effects of music on psychophysiological responses and opioid dosage in patients undergoing total knee replacement surgery.

Science.gov (United States)

Chen, Hsin-Ji; Chen, Tsung-Ying; Huang, Chiung-Yu; Hsieh, Yuan-Mei; Lai, Hui-Ling

2015-10-01

The present authors examined the effects of listening to music on psychophysiological parameters (blood pressure, heart rate, and respiratory rate) during preoperative and postoperative days and determined whether listening to music could lower pain intensity and opioid dosage during postoperative days in patients who underwent total knee replacements. This was a two group repeated measures design for 30 subjects aged 53-85 years who were scheduled for total knee replacement. Subjects were randomly assigned to either a music group or a control group. Psychophysiological parameters were obtained from patients' monitors. A visual analog scale was used to assess postoperative pain. Opioid dosage was recorded and converted to standardized units. Mann-Whitney U-test and generalized estimating equation analysis were used to compare groups. Respiratory rates while in the surgical waiting area were lower for the music group than for the control group (P = 0.02). There was no significant difference between these groups for blood pressure, heart rate, pain intensity, or opioid dosage. However, a within-group comparison showed that systolic blood pressure in the music group was significantly and consistently decreased during postoperative recovery (Wald = 9.21, P = 0.007). These results suggest that listening to music stabilized systolic blood pressure in patients during postoperative recovery. However, the effects of music on psychophysiological parameters, pain intensity, and opioid dosage in a surgical setting require further research. © 2015 The Authors. Japan Journal of Nursing Science © 2015 Japan Academy of Nursing Science.

Multi-platform whole-genome microarray analyses refine the epigenetic signature of breast cancer metastasis with gene expression and copy number.

Directory of Open Access Journals (Sweden)

Joseph Andrews

2010-01-01

Full Text Available We have previously identified genome-wide DNA methylation changes in a cell line model of breast cancer metastasis. These complex epigenetic changes that we observed, along with concurrent karyotype analyses, have led us to hypothesize that complex genomic alterations in cancer cells (deletions, translocations and ploidy are superimposed over promoter-specific methylation events that are responsible for gene-specific expression changes observed in breast cancer metastasis.We undertook simultaneous high-resolution, whole-genome analyses of MDA-MB-468GFP and MDA-MB-468GFP-LN human breast cancer cell lines (an isogenic, paired lymphatic metastasis cell line model using Affymetrix gene expression (U133, promoter (1.0R, and SNP/CNV (SNP 6.0 microarray platforms to correlate data from gene expression, epigenetic (DNA methylation, and combination copy number variant/single nucleotide polymorphism microarrays. Using Partek Software and Ingenuity Pathway Analysis we integrated datasets from these three platforms and detected multiple hypomethylation and hypermethylation events. Many of these epigenetic alterations correlated with gene expression changes. In addition, gene dosage events correlated with the karyotypic differences observed between the cell lines and were reflected in specific promoter methylation patterns. Gene subsets were identified that correlated hyper (and hypo methylation with the loss (or gain of gene expression and in parallel, with gene dosage losses and gains, respectively. Individual gene targets from these subsets were also validated for their methylation, expression and copy number status, and susceptible gene pathways were identified that may indicate how selective advantage drives the processes of tumourigenesis and metastasis.Our approach allows more precisely profiling of functionally relevant epigenetic signatures that are associated with cancer progression and metastasis.

The effect of different dosages of caffeine on endurance performance time

NARCIS (Netherlands)

Pasman, W.J.; Baak, M.A. van; Jeukendrup, A.E.; Haan, A. de

1995-01-01

The effect of different dosages of caffeine (0 - 5 - 9 - 13 mg · kg body weight-1) on endurance performance was examined. Nine well-trained cyclists participated in this study (VO2max 65.1 + 2.6 ml · kg-1 · min-1). Caffeine capsules were administered in random order and double-blind. One hour after

76 FR 22610 - Implantation or Injectable Dosage Form New Animal Drugs; Enrofloxacin

Science.gov (United States)

2011-04-22

.... FDA-2011-N-0003] Implantation or Injectable Dosage Form New Animal Drugs; Enrofloxacin AGENCY: Food... the indications for use of enrofloxacin solution in cattle, as a single injection, for the treatment... supplement to NADA 141-068 for BAYTRIL 100 (enrofloxacin), an injectable solution. The supplemental NADA...

Reducing glucocorticoid dosage improves serum osteocalcin in patients with rheumatoid arthritis-results from the TOMORROW study.

Science.gov (United States)

Tada, M; Inui, K; Sugioka, Y; Mamoto, K; Okano, T; Koike, T; Nakamura, H

2016-02-01

Decreasing the daily dose of glucocorticoids improved bone metabolic marker levels in patients with rheumatoid arthritis. However, changes in disease activity did not influence bone metabolism. Bone metabolism might thus remain uncontrolled even if disease activity is under good control. Decreasing glucocorticoid dosage appears important for improving bone metabolism. Patients with rheumatoid arthritis (RA) develop osteoporosis more frequently than healthy individuals. Bone resorption is increased and bone formation is inhibited in patients with RA, and glucocorticoid negatively affects bone metabolism. We aimed to investigate factors influencing bone metabolic markers in patients with RA. We started the 10-year prospective cohort Total Management of Risk Factors in Rheumatoid Arthritis Patients to Lower Morbidity and Mortality (TOMORROW) study in 2010. We compared changes in urinary cross-linked N-telopeptide of type I collagen (uNTx) and serum osteocalcin (OC), as markers of bone resorption and formation, respectively, in 202 RA patients and age- and sex-matched volunteers between 2010 and 2011. We also investigated factors influencing ΔuNTx and ΔOC in the RA group using multivariate analysis. Values of ΔuNTx were significantly lower in patients with RA than in healthy controls (-0.51 vs. 7.41 nmol bone collagen equivalents (BCE)/mmol creatinine (Cr); p = 0.0013), whereas ΔOC values were significantly higher in RA patients (0.94 vs. 0.37 ng/ml; p = 0.0065). Changes in prednisolone dosage correlated negatively with ΔOC (β = -0.229, p = 0.001), whereas changes in disease activity score, bisphosphonate therapy, and period of biologics therapy did not correlate significantly with ΔOC. No significant correlation was seen between ΔuNTx and change in prednisolone dosage. Decreased glucocorticoid dosage improved bone metabolic markers in RA, but disease activity, bisphosphonate therapy, and period of biologics therapy did not influence

Radiation dosages absorbed by the skin during videofluorographic examination of velopharyngeal function

International Nuclear Information System (INIS)

Ohara, Hirotoshi; Ogata, Hisao; Nakajima, Tatsuo; Sone, Kiyoaki

2008-01-01

Radiographic assessment has become essential in examining the function of the soft palate and pharyngeal walls in patients with velopharyngeal insufficiency. However, in our search of the literature, there was no report on the exposure dose during videofluorographic examination of velopharyngeal function in Japan. Radiation dosages from videofluorography were measured by attaching a glass dosimeter to the submental skin in 17 patients undergoing examination of velopharyngeal function. Sixteen patients underwent a complete videofluorographic examination. For these 16 patients, the mean time of examination was 96.4 sec; the mean radiation dosage absorbed by the skin was 14.4 mGy, equivalent to approximately 7 standard skull x-rays and lower than that during other fluoroscopic procedures. This dose was also lower than the threshold dose at which the skin damage occurs. In light of increasing concern among the general public over radiation exposure, we consider that these data should provide useful information to patients being asked to give informed consent for this examination. (author)

RP-HPLC Method for the Estimation of Nebivolol in Tablet Dosage Form

Directory of Open Access Journals (Sweden)

M. K. Sahoo

2009-01-01

Full Text Available A reverse phase HPLC method is described for the determination of nebivolol in tablet dosage form. Chromatography was carried on a Hypersil ODS C18 column using a mixture of methanol and water (80:20 v/v as the mobile phase at a flow rate of 1.0 mL/min with detection at 282 nm. Chlorzoxazone was used as the internal standard. The retention times were 3.175 min and 4.158 min for nebivolol and chlorzoxazone respectively. The detector response was linear in the concentration of 1-400 μg/mL. The limit of detection and limit of quantification was 0.0779 and 0.2361 μg/mL respectively. The percentage assay of nebivolol was 99.974%. The method was validated by determining its sensitivity, accuracy and precision. The proposed method is simple, fast, accurate and precise and hence can be applied for routine quality control of nebivolol in bulk and tablet dosage form.

Fluorometric determination of uranium in urine; Dosage fluorimetrique de l'uranium urinaire

Energy Technology Data Exchange (ETDEWEB)

Ronteix, C; Hugot, G [Commissariat a l' Energie Atomique, Saclay (France).Centre d' Etudes Nucleaires

1960-07-01

For the medical supervision of personnel the most sensitive analytical methods must be used. The fluorimetric method, enabling determinations to be made without previous concentration, is undoubtedly the quickest and most effective. This report is intended to help users of the method to avoid loss of time in the practical application. It therefore describes in great detail the material used, and also gives precise technical information acquired by experience. (author) [French] Pour la surveillance medicale du personnel, il est necessaire d'utiliser les methodes de dosages les plus sensibles. La methode fluorimetrique qui permet d'effectuer le dosage sans concentration prealable est, sans conteste, la plus rapide et la plus efficace. Le present rapport a pour but de permettre aux utilisateurs de cette methode, d'eviter des pertes de temps dans l'application pratique. Il contient donc, tres detaille, le materiel utilise ainsi que des precisions techniques acquises par l'experience. (auteur)

The effects of different enrofloxacin dosages on clinical efficacy and resistance development in chickens experimentally infected with Salmonella Typhimurium.

Science.gov (United States)

Li, Jun; Hao, Haihong; Cheng, Guyue; Wang, Xu; Ahmed, Saeed; Shabbir, Muhammad Abu Bakr; Liu, Zhenli; Dai, Menghong; Yuan, Zonghui

2017-09-15

To investigate the optimal dosage which can improve clinical efficacy and minimize resistance, pharmacokinetics/pharmacodynamics model of enrofloxacin was established. Effect of enrofloxacin treatments on clearance of Salmonella in experimentally infected chickens and simultaneously resistance selection in Salmonella and coliforms were evaluated in three treatment groups (100, PK/PD designed dosage of 4, 0.1 mg/kg b.w.) and a control group. Treatment duration was three rounds of 7-day treatment alternated with 7-day withdrawal. Results showed that 100 mg/kg b.w. of enrofloxacin completely eradicated Salmonella, but resistant coliforms (4.0-60.8%) were selected from the end of the second round's withdrawal period till the end of the experiment (days 28-42). PK/PD based dosage (4 mg/kg b.w.) effectively reduced Salmonella for the first treatment duration. However upon cessation of medication, Salmonella repopulated chickens and persisted till the end with reduced susceptibility (MIC CIP  = 0.03-0.25 mg/L). Low frequency (5-9.5%) of resistant coliforms was selected (days 39-42). Enrofloxacin at dosage of 0.1 mg/kg b.w. was not able to eliminate Salmonella and selected coliforms with slight decreased susceptibility (MIC ENR  = 0.25 mg/L). In conclusion, short time treatment (7 days) of enrofloxacin at high dosage (100 mg/kg b.w.) could be effective in treating Salmonella infection while minimizing resistance selection in both Salmonella and coliforms.

Clinical criteria for medical staff exposure and reference dosage within the Galician health Service

International Nuclear Information System (INIS)

Garcia Comesana, J.

2003-01-01

The generalised use of ionising radiation tests is making these tests become the prime cause of exposure to artificial radiation, receiving one sixth of the dosage through background radiation. (Author)

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

Science.gov (United States)

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.

Plasma levels and symptom complaints in patients maintained on daily dosage of methadone hydrochloride.

Science.gov (United States)

Horns, W H; Rado, M; Goldstein, A

1975-06-01

Plasma methadone levels, symptom complaints, and urine tests for illicit opiate use were followed weekly in 17 patients on a methadone maintenance program. There were very large differences between patients in the plasma level established at a given dosage, implying large differences in the rate of methadone metabolism. Despite virtually constant daily dosage, the plasma methadone levels fluctuated greatly from week to week and from day to day in individual patients. With rate exceptions there was no relationship between plasma methadone level and symptom complaints or between weekly chamges in plasma methadone level and changes in symptom complaints. Except possible to identify the ocassional patient with unusually low plasam methadone levels, the determination of methadone levels is not likely to be or practical value in methadone programs.

Enalapril dosage in progressive chronic nephropathy

DEFF Research Database (Denmark)

Elung-Jensen, Thomas; Heisterberg, Jens; Sonne, Jesper

2005-01-01

OBJECTIVE: In chronic renal failure, clearance of enalapril is reduced. Hence, a renoprotective effect may be achieved with lower doses than conventionally used. Since marked inter-patient variation in concentrations of enalaprilat has been shown in patients with renal failure despite equivalent...... dosage of enalapril, a direct comparison of the effect of high versus low plasma concentrations of enalaprilat on the progression of renal failure was undertaken. METHODS: Forty patients with a median glomerular filtration rate (GFR) of 17 (6-35) ml/min/1.73 m2 were studied in an open-label, randomised...... intervals by the plasma clearance of 51Cr-EDTA, and the individual rates of progression of renal failure were calculated as the slope of GFR versus time plot. RESULTS: In the high-concentration group, the median enalaprilat trough concentration was 92.9 ng/ml (21.8-371.0 ng/ml) and in the low...

A novel solid dosage form of rifampicin and isoniazid with improved functionality.

Science.gov (United States)

Gohel, Mukesh C; Sarvaiya, Krishnakant G

2007-08-24

The aim of the present investigation was to develop a novel dosage form of rifampicin and isoniazid to minimize degradation of rifampicin in acidic medium and to modulate the release of rifampicin in the stomach and isoniazid in the intestine. Gastroretentive tablets of rifampicin (150 mg) were prepared by the wet granulation method using hydroxypropyl methylcellulose, calcium carbonate, and polyethylene glycol 4000. The granules and tablets of rifampicin were characterized. Hard gelatin capsules (size 4) containing a compacted mass of isoniazid (150 mg) and dicalcium phosphate (75 mg) were enteric coated. Two tablets of rifampicin and 1 capsule (size 4) of isoniazid were put into a hard gelatin capsule (size 00). The in vitro drug release and in vitro drug degradation studies were performed. Rifampicin was released over 4 hours by zero-order kinetics from the novel dosage form. More than 90% of isoniazid was released in alkaline medium in 30 minutes. The results of dissolution studies with the US Pharmacopeia XXIII method revealed that a substantial amount of rifampicin was degraded from the immediate release capsule containing rifampicin and isoniazid powder owing to drug accumulation in the dissolution vessel and also to the presence of isoniazid. The degradation of rifampicin to 3-formyl rifampicin SV (3FRSV) was arrested (3.6%-4.8% degradation of rifampicin at 4 hours) because of the minimization of physical contact between the 2 drugs and controlled release of rifampicin in acidic medium in the modified Rossett-Rice apparatus. This study concludes that the problem of rifampicin degradation can be alleviated to a certain extent by this novel dosage form.

Prevalent Role of Gene Features in Determining Evolutionary Fates of Whole-Genome Duplication Duplicated Genes in Flowering Plants1[W][OA

Science.gov (United States)

Jiang, Wen-kai; Liu, Yun-long; Xia, En-hua; Gao, Li-zhi

2013-01-01

The evolution of genes and genomes after polyploidization has been the subject of extensive studies in evolutionary biology and plant sciences. While a significant number of duplicated genes are rapidly removed during a process called fractionation, which operates after the whole-genome duplication (WGD), another considerable number of genes are retained preferentially, leading to the phenomenon of biased gene retention. However, the evolutionary mechanisms underlying gene retention after WGD remain largely unknown. Through genome-wide analyses of sequence and functional data, we comprehensively investigated the relationships between gene features and the retention probability of duplicated genes after WGDs in six plant genomes, Arabidopsis (Arabidopsis thaliana), poplar (Populus trichocarpa), soybean (Glycine max), rice (Oryza sativa), sorghum (Sorghum bicolor), and maize (Zea mays). The results showed that multiple gene features were correlated with the probability of gene retention. Using a logistic regression model based on principal component analysis, we resolved evolutionary rate, structural complexity, and GC3 content as the three major contributors to gene retention. Cluster analysis of these features further classified retained genes into three distinct groups in terms of gene features and evolutionary behaviors. Type I genes are more prone to be selected by dosage balance; type II genes are possibly subject to subfunctionalization; and type III genes may serve as potential targets for neofunctionalization. This study highlights that gene features are able to act jointly as primary forces when determining the retention and evolution of WGD-derived duplicated genes in flowering plants. These findings thus may help to provide a resolution to the debate on different evolutionary models of gene fates after WGDs. PMID:23396833

Maximum a posteriori Bayesian estimation of mycophenolic Acid area under the concentration-time curve: is this clinically useful for dosage prediction yet?

Science.gov (United States)

Staatz, Christine E; Tett, Susan E

2011-12-01

This review seeks to summarize the available data about Bayesian estimation of area under the plasma concentration-time curve (AUC) and dosage prediction for mycophenolic acid (MPA) and evaluate whether sufficient evidence is available for routine use of Bayesian dosage prediction in clinical practice. A literature search identified 14 studies that assessed the predictive performance of maximum a posteriori Bayesian estimation of MPA AUC and one report that retrospectively evaluated how closely dosage recommendations based on Bayesian forecasting achieved targeted MPA exposure. Studies to date have mostly been undertaken in renal transplant recipients, with limited investigation in patients treated with MPA for autoimmune disease or haematopoietic stem cell transplantation. All of these studies have involved use of the mycophenolate mofetil (MMF) formulation of MPA, rather than the enteric-coated mycophenolate sodium (EC-MPS) formulation. Bias associated with estimation of MPA AUC using Bayesian forecasting was generally less than 10%. However some difficulties with imprecision was evident, with values ranging from 4% to 34% (based on estimation involving two or more concentration measurements). Evaluation of whether MPA dosing decisions based on Bayesian forecasting (by the free website service https://pharmaco.chu-limoges.fr) achieved target drug exposure has only been undertaken once. When MMF dosage recommendations were applied by clinicians, a higher proportion (72-80%) of subsequent estimated MPA AUC values were within the 30-60 mg · h/L target range, compared with when dosage recommendations were not followed (only 39-57% within target range). Such findings provide evidence that Bayesian dosage prediction is clinically useful for achieving target MPA AUC. This study, however, was retrospective and focussed only on adult renal transplant recipients. Furthermore, in this study, Bayesian-generated AUC estimations and dosage predictions were not compared

Safety of higher dosages of Viscum album L. in animals and humans - systematic review of immune changes and safety parameters

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Kiene Helmut

2011-08-01

Full Text Available Abstract Background Viscum album L extracts (VAE, mistletoe and isolated mistletoe lectins (ML have immunostimulating properties and a strong dose-dependent cytotoxic activity. They are frequently used in complementary cancer treatment, mainly to improve quality of life, but partly also to influence tumour growth, especially by injecting VAE locally and in high dosage. The question is raised whether these higher dosages can induce any harm or immunosuppressive effects. Methods Systematic review of all experiments and clinical studies investigating higher dosages of VAE in animals and humans (Viscum album > 1 mg in humans corresponding to > 0.02 mg/kg in animals or ML > 1 ng/kg and assessing immune parameters or infections or adverse drug reactions. Results 69 clinical studies and 48 animal experiments reported application of higher doses of VAE or ML and had assessed immune changes and/or harm. In these studies, Viscum album was applied in dosages up to 1500 mg in humans and 1400 mg/kg in animals, ML was applied up to 6.4 μg/kg in humans and in animals up to 14 μg/kg subcutaneously, 50 μg/kg nasally and 500 μg/kg orally. A variety of immune parameters showed fluctuating or rising outcomes, but no immunosuppressive effect. Side effects consisted mainly of dose-dependent flu-like symptoms (FLS, fever, local reactions at the injection site and various mild unspecific effects. Occasionally, allergic reactions were reported. After application of high doses of recombinant ML, reversible hepatotoxicity was observed in some cases. Conclusions Application of higher dosages of VAE or ML is not accompanied by immunosuppression; altogether VAE seems to exhibit low risk but should be monitored by clinicians when applied in high dosages.

Rheology as a tool for evaluation of melt processability of innovative dosage forms

DEFF Research Database (Denmark)

Aho, Johanna Maaria; Boetker, Johan P; Baldursdottir, Stefania

2015-01-01

) printing, will have an increasingly important role when designing products for flexible dosing, since dosage forms based on compacting of a given powder mixture do not enable manufacturing of optimal pharmaceutical products for personalized treatments. The melt processability of polymers and API...

A Novel Disintegration Tester for Solid Dosage Forms Enabling Adjustable Hydrodynamics.

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Kindgen, Sarah; Rach, Regine; Nawroth, Thomas; Abrahamsson, Bertil; Langguth, Peter

2016-08-01

A modified in vitro disintegration test device was designed that enables the investigation of the influence of hydrodynamic conditions on disintegration of solid oral dosage forms. The device represents an improved derivative of the compendial PhEur/USP disintegration test device. By the application of a computerized numerical control, a variety of physiologically relevant moving velocities and profiles can be applied. With the help of computational fluid dynamics, the hydrodynamic and mechanical forces present in the probe chamber were characterized for a variety of device moving speeds. Furthermore, a proof of concept study aimed at the investigation of the influence of hydrodynamic conditions on disintegration times of immediate release tablets. The experiments demonstrated the relevance of hydrodynamics for tablet disintegration, especially in media simulating the fasted state. Disintegration times increased with decreasing moving velocity. A correlation between experimentally determined disintegration times and computational fluid dynamics predicted shear stress on tablet surface was established. In conclusion, the modified disintegration test device is a valuable tool for biorelevant in vitro disintegration testing of solid oral dosage forms. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Effect of 18F-FDG dosage alternation on final PET image

International Nuclear Information System (INIS)

Yin Dayi; Yao Shulin; Chen Yingmao; Shao Mingzhe; Tian Jiahe

2002-01-01

Objective: To assess PET reconstructed image effected by different 18 F-FDG dosages with quantitative and qualitative analysis. Methods: To perform PET phantom acquisition by routine clinical parameters after filled with different doses of 18 F-FDG solution. An identical slice was extracted from reconstructed image for doing following analysis: the hot area standard uptake value (SUV), the ratio of hot area to cold area, the standard deviation on background area, the ratio of true coincidence to random. Results: 296 MBq: The image uniformity was terribly worse, T/R=0.83, other indexes were irregular. 148 MBq: The image presentation looked like the image without attenuation correction, T/R=1.64, other indexes were moderate. 74, 37 and 18.5 MBq: The images were with excellent uniformity, resolution and contrast, the background noise was suitable, all of the quantitative indexes were good. 9.25 and 4.625 MBq: The uniformity and resolution was degraded terribly because of the higher noise and lower information. Conclusion: Combining above results with other considerations, such as radiation exposure, information amount and acquisition time, the authors think the optimal dosage should be 4.625-11.1 MBq/kg

Preparation and characterization of solid oral dosage forms containing soy isoflavones

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Stela R. de Oliveira

2013-02-01

Full Text Available Soy isoflavones have been extensively used for menopausal symptoms and prevention of hormone-related cancer, osteoporosis and cardiovascular diseases. Commercially available forms of isoflavones include supplements, capsules and tablets. However, the non-standardization of soy isoflavones extracts and different dissolution profiles of these solid dosage forms highlight the need of additional studies on the development of well characterized pharmaceutical dosage forms of isoflavones. In this work, immediate release oral tablets of soy isoflavones were obtained and evaluated. Genistein and daidzein, were the main constituents of the dried soy extract. Preparation of the tables was accomplished in a rotary tableting machine following either a dry mixture for direct compression or wet granulation with different excipients. Powder, granules and tablets were evaluated for several parameters, including flow properties, Carr and Hausner indexes, hardness, friability, disintegration time and drug release profile. Also, a fast and validated HPLC analytical method for both genistein and daidzein was developed. Formulations containing sodium croscarmellose and sodium dodecyl sulfate resulted in better flowability as indicated by the flow rate and angle of repose, faster disintegration time and immediate release dissolution profile.

Effective Dosage of Midazolam to Erase the Memory of Vascular Pain During Propofol Administration.

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Boku, Aiji; Inoue, Mika; Hanamoto, Hiroshi; Oyamaguchi, Aiko; Kudo, Chiho; Sugimura, Mitsutaka; Niwa, Hitoshi

Intravenous sedation with propofol is often administered to anxious patients in dental practice. Pain on injection of propofol is a common adverse effect. This study aimed to determine the age-adjusted doses of midazolam required to erase memory of vascular pain of propofol administration and assess whether the Ramsay Sedation Scale (RSS) after the pretreatment of midazolam was useful to predict amnesia of the vascular pain of propofol administration. A total of 246 patients with dental phobia requiring dental treatment under intravenous sedation were included. Patients were classified according to their age: 30s, 40s, 50s, and 60s. Three minutes after administration of a predetermined dose of midazolam, propofol was infused continuously. After completion of the dental procedure, patients were interviewed about the memory of any pain or discomfort in the injection site or forearm. The dosage of midazolam was determined using the Dixon up-down method. The first patient was administered 0.03 mg/kg, and if memory of vascular pain remained, the dosage was increased by 0.01 mg/kg for the next patient, and then if the memory was erased, the dosage was decreased by 0.01 mg/kg. The effective dosage of midazolam in 95% of each age group for erasing the memory of propofol vascular pain (ED95) was determined using logistic analysis. The accuracy of RSS to predict the amnesia of injection pain was assessed by receiver operating characteristic (ROC) analysis. The ED95 of midazolam to erase the memory of propofol vascular pain was 0.061 mg/kg in patients in their 30s, 0.049 mg/kg in patients in their 40s, 0.033 mg/kg in patients in their 50s, and 0.033 mg/kg in patients in their 60s. The area under the ROC curve was 0.31. The ED95 of midazolam required to erase the memory of propofol vascular pain demonstrated a downward trend with age. On the other hand, it was impossible to predict the amnesia of propofol vascular pain using the RSS.

Short-Term Dosage Regimen for Stimulation-Induced Long-Lasting Desynchronization

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Thanos Manos

2018-04-01

Full Text Available In this paper, we computationally generate hypotheses for dose-finding studies in the context of desynchronizing neuromodulation techniques. Abnormally strong neuronal synchronization is a hallmark of several brain disorders. Coordinated Reset (CR stimulation is a spatio-temporally patterned stimulation technique that specifically aims at disrupting abnormal neuronal synchrony. In networks with spike-timing-dependent plasticity CR stimulation may ultimately cause an anti-kindling, i.e., an unlearning of abnormal synaptic connectivity and neuronal synchrony. This long-lasting desynchronization was theoretically predicted and verified in several pre-clinical and clinical studies. We have shown that CR stimulation with rapidly varying sequences (RVS robustly induces an anti-kindling at low intensities e.g., if the CR stimulation frequency (i.e., stimulus pattern repetition rate is in the range of the frequency of the neuronal oscillation. In contrast, CR stimulation with slowly varying sequences (SVS turned out to induce an anti-kindling more strongly, but less robustly with respect to variations of the CR stimulation frequency. Motivated by clinical constraints and inspired by the spacing principle of learning theory, in this computational study we propose a short-term dosage regimen that enables a robust anti-kindling effect of both RVS and SVS CR stimulation, also for those parameter values where RVS and SVS CR stimulation previously turned out to be ineffective. Intriguingly, for the vast majority of parameter values tested, spaced multishot CR stimulation with demand-controlled variation of stimulation frequency and intensity caused a robust and pronounced anti-kindling. In contrast, spaced CR stimulation with fixed stimulation parameters as well as singleshot CR stimulation of equal integral duration failed to improve the stimulation outcome. In the model network under consideration, our short-term dosage regimen enables to robustly induce

Short-Term Dosage Regimen for Stimulation-Induced Long-Lasting Desynchronization.

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Manos, Thanos; Zeitler, Magteld; Tass, Peter A

2018-01-01

In this paper, we computationally generate hypotheses for dose-finding studies in the context of desynchronizing neuromodulation techniques. Abnormally strong neuronal synchronization is a hallmark of several brain disorders. Coordinated Reset (CR) stimulation is a spatio-temporally patterned stimulation technique that specifically aims at disrupting abnormal neuronal synchrony. In networks with spike-timing-dependent plasticity CR stimulation may ultimately cause an anti-kindling, i.e., an unlearning of abnormal synaptic connectivity and neuronal synchrony. This long-lasting desynchronization was theoretically predicted and verified in several pre-clinical and clinical studies. We have shown that CR stimulation with rapidly varying sequences (RVS) robustly induces an anti-kindling at low intensities e.g., if the CR stimulation frequency (i.e., stimulus pattern repetition rate) is in the range of the frequency of the neuronal oscillation. In contrast, CR stimulation with slowly varying sequences (SVS) turned out to induce an anti-kindling more strongly, but less robustly with respect to variations of the CR stimulation frequency. Motivated by clinical constraints and inspired by the spacing principle of learning theory, in this computational study we propose a short-term dosage regimen that enables a robust anti-kindling effect of both RVS and SVS CR stimulation, also for those parameter values where RVS and SVS CR stimulation previously turned out to be ineffective. Intriguingly, for the vast majority of parameter values tested, spaced multishot CR stimulation with demand-controlled variation of stimulation frequency and intensity caused a robust and pronounced anti-kindling. In contrast, spaced CR stimulation with fixed stimulation parameters as well as singleshot CR stimulation of equal integral duration failed to improve the stimulation outcome. In the model network under consideration, our short-term dosage regimen enables to robustly induce long

Apparatus comprising trace element dosage and method for treating raw water in biofilter

DEFF Research Database (Denmark)

2015-01-01

the inlet (2) to the outlet (3) or in the reverse direction, - the trace element dosage device (13) is positioned upstream of the porous filter material and microbial biomass and is configured to dose trace element(s) to the water flowing through the filter. A method for treating raw water by microbial......Apparatus for treating raw water in a biofilter The present invention relates to an apparatus in which raw water is treated through microbial activity where microbial activity is controlled by nutrients and other parameters. Some of the nutrients controlling the microbial activity are trace...... elements such as certain metals (Cu, Co, Cr, Mo, Ni, W, Zn or a mixture thereof). The apparatus comprising - a volume provided with an inlet (2) for raw water and an outlet (3) for water having been subjected to microbial activity, a filter and a trace element dosage device (13) are placed in this volume...

Malavefes: A computational voice-enabled malaria fuzzy informatics software for correct dosage prescription of anti-malarial drugs

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Olugbenga O. Oluwagbemi

2018-04-01

Full Text Available Malaria is one of the infectious diseases consistently inherent in many Sub-Sahara African countries. Among the issues of concern are the consequences of wrong diagnosis and dosage administration of anti-malarial drugs on sick patients; these have resulted into various degrees of complications ranging from severe headaches, stomach and body discomfort, blurred vision, dizziness, hallucinations, and in extreme cases, death. Many expert systems have been developed to support different infectious disease diagnoses, but not sure of any yet, that have been specifically designed as a voice-based application to diagnose and translate malaria patients’ symptomatic data for pre-laboratory screening and correct prescription of proper dosage of the appropriate medication. We developed Malavefes, (a malaria voice-enabled computational fuzzy expert system for correct dosage prescription of anti-malarial drugs using Visual Basic.NET., and Java programming languages. Data collation for this research was conducted by survey from existing literature and interview from public health experts. The database for this malaria drug informatics system was implemented using Microsoft Access. The Root Sum Square (RSS was implemented as the inference engine of Malavefes to make inferences from rules, while Centre of Gravity (CoG was implemented as the defuzzification engine. The drug recommendation module was voice-enabled. Additional anti-malaria drug expiration validation software was developed using Java programming language. We conducted a user-evaluation of the performance and user-experience of the Malavefes software. Keywords: Informatics, Bioinformatics, Fuzzy, Anti-malaria, Voice computing, Dosage prescription

Cancer therapy leading to state of cancer metabolism depression for efficient operation of small dosage cytotoxic drugs

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Ponizovskiy MR

2015-04-01

Full Text Available “Prolonged medical starvation” as the method of cancer therapy was borrowed from folk healers Omelchenko A and Breuss R. Author was convinced in efficiency of this method of cancer treatment via examination of cured patients and on own experience. The mechanism of this method of cancer therapy operates via Warburg effect targeting that promotes efficient cancer treatment with small cytotoxic drugs. Just it was described the mechanism of Warburg effect as well as mechanism transmutation of mitochondrial function in cancer metabolism which are exhibited in connection with operation of described method cancer therapy. There were described the biochemical and biophysical mechanisms of formations resistance to some cytotoxic drugs and recurrence cancer disease after disease remission which occur sometimes as result of treatment with great dosage of cytotoxic drugs. Also it was described the benefits of use the method “Prolonged medical starvation” with decreased dosage of cytotoxic drugs for cancer treatment. The significance of this work that it was substantiated the mechanism operation of combination “Prolonged medical starvation” with small dosages cytotoxic drugs of cancer treatment, which mechanism leads to prevention recurrence cancer disease and resistance to anticancer drugs in comparison with intensive anticancer chemotherapy with great dosages of cytotoxic drugs in cancer therapy. Also the offered concepts of cancer therapy mechanism gave possibility to explain mechanisms of some results of experiments eliminating the doubts of the authors these experiments.

Vitamin D supplementation in inflammatory bowel disease: the role of dosage and patient compliance.

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Kojecky, V; Adamikova, A; Klimek, P

2016-01-01

Vitamin D substitution is recommended in patients with inflammatory bowel disease. Specific guidelines are lacking. The aim of this study was to assess the effect of vitamin D supplementation with respect to dosage and patient compliance. A prospective cohort study of 167 Crohn disease/ulcerative colitis outpatients. Patients were screened for serum vitamin D (25OHD2+3) at the end of summer and in late winter. Demographic data, history of vitamin D supplementation were recorded and matched with prescription records. A total of 57 subjects used vitamin D supplementation (mean dose 1104 IU/day). 25OHD2+3 levels were lower (p compliance with vitamin D supplementation was low, however this fact did not significantly contribute to the degree of vitamin D deficiency in this dosage (Tab. 3, Fig. 1, Ref. 21).

A Validated RP-HPLC Method for the Determination of Atazanavir in Pharmaceutical Dosage Form

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K. Srinivasu

2011-01-01

Full Text Available A validated RP HPLC method for the estimation of atazanavir in capsule dosage form on YMC ODS 150 × 4.6 mm, 5 μ column using mobile phase composition of ammonium dihydrogen phosphate buffer (pH 2.5 with acetonitrile (55:45 v/v. Flow rate was maintained at 1.5 mL/min with 288 nm UV detection. The retention time obtained for atazanavir was at 4.7 min. The detector response was linear in the concentration range of 30 - 600 μg/mL. This method has been validated and shown to be specific, sensitive, precise, linear, accurate, rugged, robust and fast. Hence, this method can be applied for routine quality control of atazanavir in capsule dosage forms as well as in bulk drug.

Semi-Solid and Solid Dosage Forms for the Delivery of Phage Therapy to Epithelia

Science.gov (United States)

Petrovski, Steve; Chan, Hiu Tat; Angove, Michael J.; Tucci, Joseph

2018-01-01

The delivery of phages to epithelial surfaces for therapeutic outcomes is a realistic proposal, and indeed one which is being currently tested in clinical trials. This paper reviews some of the known research on formulation of phages into semi-solid dosage forms such as creams, ointments and pastes, as well as solid dosage forms such as troches (or lozenges and pastilles) and suppositories/pessaries, for delivery to the epithelia. The efficacy and stability of these phage formulations is discussed, with a focus on selection of optimal semi-solid bases for phage delivery. Issues such as the need for standardisation of techniques for formulation as well as for assessment of efficacy are highlighted. These are important when trying to compare results from a range of experiments and across different delivery bases. PMID:29495355

Particle Engineering Via Mechanical Dry Coating in the Design of Pharmaceutical Solid Dosage Forms.

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Qu, Li; Morton, David A V; Zhou, Qi Tony

2015-01-01

Cohesive powders are problematic in the manufacturing of pharmaceutical solid dosage forms because they exhibit poor flowability, fluidization and aerosolization. These undesirable bulk properties of cohesive powders represent a fundamental challenge in the design of efficient pharmaceutical manufacturing processes. Recently, mechanical dry coating has attracted increasing attention as it can improve the bulk properties of cohesive powders in a cheaper, simpler, safer and more environment-friendly way than the existing solvent-based counterparts. In this review, mechanical dry coating techniques are outlined and their potential applications in formulation and manufacturing of pharmaceutical solid dosage forms are discussed. Reported data from the literature have shown that mechanical dry coating holds promise for the design of superior pharmaceutical solid formulations or manufacturing processes by engineering the interfaces of cohesive powders in an efficient and economical way.

Evidence for oral agmatine sulfate safety--a 95-day high dosage pilot study with rats.

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Gilad, Gad M; Gilad, Varda H

2013-12-01

Agmatine, decarboxylated arginine, exerts beneficial effects in various experimental disease models. Clinical trials indicate the safety and effectiveness of short-term (up to 21 days) high dose regimens of oral agmatine sulfate, but longer term studies are lacking. This pilot study undertook to assess the safety of a longer term high dosage oral agmatine sulfate in laboratory rats. Adult Wistar rats consumed 5.3 g/l agmatine sulfate in their drinking water for 95 days, a regimen estimated to result in a daily dosage of absorbed agmatine of about 100mg/kg. Animals' body weight, water consumption and blood pressure were periodically measured, and general cage behavior, fur appearance, urination and feces appearance monitored. These parameters were also determined at 20 days after treatment cessation (day 115). On days 95 and 115, animals were euthanized for gross necropsy assessment. Agmatine-treated rats showed slight, but significant reductions in body weight and blood pressure, and reduced water consumption during treatment, which recovered completely within 20 days after treatment cessation. Otherwise, no abnormal behaviors or organ pathologies were observed. These findings are first to suggest apparent safety of sub-chronic high dosage dietary agmatine sulfate in laboratory rats, thus lending further support to the therapeutic applications of agmatine. Copyright © 2013 Elsevier Ltd. All rights reserved.

parkin mutation dosage and the phenomenon of anticipation: a molecular genetic study of familial parkinsonism

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Schellenberg Gerard D

2005-02-01

Full Text Available Abstract Background parkin mutations are a common cause of parkinsonism. Possessing two parkin mutations leads to early-onset parkinsonism, while having one mutation may predispose to late-onset disease. This dosage pattern suggests that some parkin families should exhibit intergenerational variation in age at onset resembling anticipation. A subset of familial PD exhibits anticipation, the cause of which is unknown. The aim of this study was to determine if anticipation was due to parkin mutation dosage. Methods We studied 19 kindreds that had early-onset parkinsonism in the offspring generation, late-onset parkinsonism in the parent generation, and ≥ 20 years of anticipation. We also studied 28 early-onset parkinsonism cases without anticipation. Patients were diagnosed by neurologists at a movement disorder clinic. parkin analysis included sequencing and dosage analysis of all 12 exons. Results Only one of 19 cases had compound parkin mutations, but contrary to our postulate, the affected relative with late-onset parkinsonism did not have a parkin mutation. In effect, none of the anticipation cases could be attributed to parkin. In contrast, 21% of early-onset parkinsonism patients without anticipation had parkin mutations. Conclusion Anticipation is not linked to parkin, and may signify a distinct disease entity.

Use of fluorescence spectroscopy to control ozone dosage in recirculating aquaculture systems

DEFF Research Database (Denmark)

Spiliotopoulou, Aikaterini; Martin, Richard; Pedersen, Lars-Flemming

2017-01-01

, in order to optimise ozonation treatment. Water samples from six different Danish facilities (two rearing units from a commercial trout RAS, a commercial eel RAS, a pilot RAS and two marine water aquariums) were treated with different O3 dosages (1.0–20.0 mg/L ozone) in bench-scale experiments, following...

76 FR 81806 - Ophthalmic and Topical Dosage Form New Animal Drugs; Ivermectin Topical Solution

Science.gov (United States)

2011-12-29

.... FDA-2011-N-0003] Ophthalmic and Topical Dosage Form New Animal Drugs; Ivermectin Topical Solution... solution of ivermectin. DATES: This rule is effective December 29, 2011. FOR FURTHER INFORMATION CONTACT... ANADA 200-318 for [[Page 81807

Dry coating of solid dosage forms: an overview of processes and applications.

Science.gov (United States)

Foppoli, Anastasia Anna; Maroni, Alessandra; Cerea, Matteo; Zema, Lucia; Gazzaniga, Andrea

2017-12-01

Dry coating techniques enable manufacturing of coated solid dosage forms with no, or very limited, use of solvents. As a result, major drawbacks associated with both organic solvents and aqueous coating systems can be overcome, such as toxicological, environmental, and safety-related issues on the one hand as well as costly drying phases and impaired product stability on the other. The considerable advantages related to solventless coating has been prompting a strong research interest in this field of pharmaceutics. In the article, processes and applications relevant to techniques intended for dry coating are analyzed and reviewed. Based on the physical state of the coat-forming agents, liquid- and solid-based techniques are distinguished. The former include hot-melt coating and coating by photocuring, while the latter encompass press coating and powder coating. Moreover, solventless techniques, such as injection molding and three-dimensional printing by fused deposition modeling, which are not purposely conceived for coating, are also discussed in that they would open new perspectives in the manufacturing of coated-like dosage forms.

Continuous powder feeding for pharmaceutical solid dosage form manufacture: a short review.

Science.gov (United States)

Blackshields, Caroline A; Crean, Abina M

2018-07-01

There has been a noticeable shift from pharmaceutical batch processing towards a more continuous mode of manufacture for solid oral dosage forms. Continuous solid oral dose processes would not be possible in the absence of a highly accurate feeding system. The performance of feeders defines the content of formulations and is therefore a critical operation in continuous manufacturing of solid dosage forms. It was the purpose of this review to review the role of the initial powder feeding step in a continuous manufacturing process. Different feeding mechanisms are discussed with a particular emphasis on screw controlled loss in weight (LIW) feeding. The importance of understanding the physical properties of the raw materials and its impact on the feeding process is reviewed. Prior knowledge of materials provides an initial indication of how the powders will behave through processing and facilitates in the selection of the most suitable (i) feeder (capacity), (ii) feeding mechanism, and (iii) in the case of screw feeder - screw type. The studies identified in this review focus on the impact of material on powder feeding performance.

Warfarin dosage response related pharmacogenetics in Chinese population.

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Siyue Li

Full Text Available As the most frequently prescribed anticoagulant, warfarin has large inter-individual variability in dosage. Genetic polymorphisms could largely explain the differences in dosage requirement. rs9923231 (VKORC1, rs7294 (VKORC1, rs1057910 (CYP2C9, rs2108622 (CYP4F2, and rs699664 (GGCX involved in the warfarin action mechanism and the circulatory vitamin K were selected to investigate their polymorphism characteristics and their effects on the pharmacodynamics and pharmacokinetics of warfarin in Chinese population.220 patients with cardiac valve replacement were recruited. International normalized ratio and plasma warfarin concentrations were determined. The five genetic polymorphisms were genotyping by pyro-sequencing. The relationships of maintenance dose, plasma warfarin concentration and INR were assessed among groups categorized by genotypes.rs9923231 and rs7294 in VKORC1 had the analogous genotype frequencies (D': 0.969. 158 of 220 recruited individuals had the target INR (1.5-2.5. Patients with AA of rs9923231 and CC of rs7294 required a significantly lower maintenance dose and plasma concentration than those with AG and TC, respectively. The mean weekly maintenance dose was also significantly lower in CYP2C9 rs1057910 mutated heterozygote than in patients with the wild homozygote. Eliminating the influence from environment factors (age, body weight and gender, rs9923231 and rs1057910 could explain about 32.0% of the variability in warfarin maintenance dose; rs7294 could explain 26.7% of the variability in plasma concentration. For patients with allele G of rs9923231 and allele T of rs7294, higher plasma concentration was needed to achieve the similar goal INR.A better understanding of the genetic variants in individuals can be the foundation of warfarin dosing algorithm and facilitate the reasonable and effective use of warfarin in Chinese.

The effect of miscellaneous oral dosage forms on the environmental pollution of sulfonamides in pig holdings.

Science.gov (United States)

Stahl, Jessica; Zessel, Katrin; Schulz, Jochen; Finke, Jan Henrik; Müller-Goymann, Christel Charlotte; Kietzmann, Manfred

2016-04-01

Due to antibiotic treatment of humans and animals, the prevalence of bacterial resistances increases worldwide. Especially in livestock farming, large quantities of faeces contaminated with antibiotics pose a risk of the carryover of the active ingredient to the environment. Accordingly, the aim of the present study was the evaluation of the benefit of different oral dosage forms (powder, pellets, granula) in pigs concerning the environmental pollution of sulfadiazine. Two subtherapeutic dosages were evaluated in powder mixtures to gain information about their potential to pollute the pig barn. Furthermore, a new group of pigs was kept in the stable after powder feeding of another pig group to determine the possible absorption of environmentally distributed antibiotics. Pigs were orally treated with three dosage forms. Simultaneously, sedimentation and airborne dust were collected and plasma and urine levels were determined. All formulations result in comparable plasma and urine levels, but massive differences in environmental pollution (powder > pellets, granula). Pigs housing in a contaminated barn exhibit traces of sulfadiazine in plasma and urine. Using pharmaceutical formulations like pellets or granula, the environmental pollution of sulfonamides can significantly be diminished due to massive dust reduction during feeding.

Maximum Recommended Dosage of Lithium for Pregnant Women Based on a PBPK Model for Lithium Absorption

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Scott Horton

2012-01-01

Full Text Available Treatment of bipolar disorder with lithium therapy during pregnancy is a medical challenge. Bipolar disorder is more prevalent in women and its onset is often concurrent with peak reproductive age. Treatment typically involves administration of the element lithium, which has been classified as a class D drug (legal to use during pregnancy, but may cause birth defects and is one of only thirty known teratogenic drugs. There is no clear recommendation in the literature on the maximum acceptable dosage regimen for pregnant, bipolar women. We recommend a maximum dosage regimen based on a physiologically based pharmacokinetic (PBPK model. The model simulates the concentration of lithium in the organs and tissues of a pregnant woman and her fetus. First, we modeled time-dependent lithium concentration profiles resulting from lithium therapy known to have caused birth defects. Next, we identified maximum and average fetal lithium concentrations during treatment. Then, we developed a lithium therapy regimen to maximize the concentration of lithium in the mother’s brain, while maintaining the fetal concentration low enough to reduce the risk of birth defects. This maximum dosage regimen suggested by the model was 400 mg lithium three times per day.

Effects of maternal psychotropic drug dosage on birth outcomes

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Michielsen LA

2013-12-01

Full Text Available Laura A Michielsen,1 Frank MMA van der Heijden,1 Paddy KC Janssen,2 Harold JH Kuijpers11Vincent van Gogh Institute for Psychiatry, Venlo, the Netherlands; 2Department of Pharmacy, VieCuri Medical Centre, Venlo, the NetherlandsBackground: The aim of this retrospective study was to explore the relationship between psychotropic medication dosage and birth outcomes.Methods: A total of 136 women were enrolled, who had an active mental disorder, were taking medication to prevent a relapse, or had a history of postpartum depression or psychosis. Medication use was evaluated for the three trimesters and during labor. Based on the defined daily dose, medication use was classified into three groups. Primary outcome variables included the infant gestational age at birth, birth weight, and Apgar scores at one and 5 minutes.Results: Our study showed a significantly higher incidence of Apgar score ≤7 at 5 minutes in women taking psychotropic drugs as compared with the group taking no medication, respectively (16.3% versus 0.0%, P=0.01. There was no significant difference between the two groups in Apgar score at one minute or in gestational age and birth weight. The results showed no significant differences in gestational age, birth weight, or Apgar scores for a low–intermediate or high dose of a selective serotonin reuptake inhibitor and for a low or intermediate dose of an antipsychotic.Conclusion: This study does not indicate a relationship between doses of selective serotonin reuptake inhibitors and antipsychotics and adverse neonatal outcomes.Keywords: pregnancy, psychotropic medication, dosage, birth outcomes

Evaluating dosage effects for the positive action program: How implementation impacts internalizing symptoms, aggression, school hassles, and self-esteem.

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Smokowski, Paul R; Guo, Shenyang; Wu, Qi; Evans, Caroline B R; Cotter, Katie L; Bacallao, Martica

2016-01-01

Positive Action (PA) is a school-based intervention for elementary-, middle-, and high-school students that aims to decrease problem behaviors (e.g., violence, substance use) and increase positive behaviors (e.g., academic achievement, school engagement). PA has a long history of documented success achieving these aims, making it an Evidence Based Practice (EBP). Intervention research on EBP's has established the importance of implementation fidelity, especially with regard to program dosage; failure to properly implement an EBP can have negative consequences on targeted outcomes, especially if participants are exposed to a low dosage of the program (e.g., fewer lessons than specified). Much of the current research on PA has neglected to examine how program dosage impacts PA's effect on targeted outcomes. Using propensity score models, multiple imputation, and a 2-level hierarchical linear model, the current study fills this gap and examines how different dosages of PA as measured by years participating in PA and number of PA lessons, impacts adolescent internalizing symptoms, aggression, perceptions of school hassles, and self-esteem over a 3-year period. The current sample included middle school students in grades 6, 7, and 8 (N = 5,894). The findings indicate that students who received 3 years of the PA intervention and a high number of PA lessons had a significantly higher self-esteem score than those who received 0 years of PA or zero lessons. Participants who received 1 year of PA also reported significantly lower school hassle scores than those who received 0 years. Dosage had no statistically significant effects on aggression or internalizing score. Implications are discussed. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Evaluation on the influence of electrocardiograph modulated milliampere on image quality and exposure dosage of volume CT heart scan

International Nuclear Information System (INIS)

Zhang Sen; Du Xiangke; Li Jianyin

2006-01-01

Objective: To find out whether the use of ECG modulated current (mA) will influence image quality and to decide whether the electrocardiograph (ECG) modulated mA will effectively reduce the exposure dosage. Methods: The cardiac pulsating phantom was set at three speed levels, i.e. high, medium, and low speed so as to simulate different heart rates. The phantom was scanned with ECG modulated mA turned on and off, and the exposure dosage of each scan sequence was documented. The images were reconstructed with reconstruction algorithm that matched the different levels of heart rate. CT values and their corresponding standard deviations at uniform areas on the images and the variation of the CT values at different locations were measured. The results from the two groups with and without ECG modulated mA were analyzed. Results: Under the same level of heart rate, the exposure dosage was remarkably reduced when the ECG modulated mA was on than when it was off. Statistical analysis showed no significant difference (P>0.05) between the images from the two groups. Conclusion: When scanning the heart with volume CT (VCT), the application of ECG modulated mA can effectively reduce the exposure dosage without sacrificing the image quality. (authors)

Artificial Neural Networks in Evaluation and Optimization of Modified Release Solid Dosage Forms

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Zorica Djurić

2012-10-01

Full Text Available Implementation of the Quality by Design (QbD approach in pharmaceutical development has compelled researchers in the pharmaceutical industry to employ Design of Experiments (DoE as a statistical tool, in product development. Among all DoE techniques, response surface methodology (RSM is the one most frequently used. Progress of computer science has had an impact on pharmaceutical development as well. Simultaneous with the implementation of statistical methods, machine learning tools took an important place in drug formulation. Twenty years ago, the first papers describing application of artificial neural networks in optimization of modified release products appeared. Since then, a lot of work has been done towards implementation of new techniques, especially Artificial Neural Networks (ANN in modeling of production, drug release and drug stability of modified release solid dosage forms. The aim of this paper is to review artificial neural networks in evaluation and optimization of modified release solid dosage forms.

Feasibility study on low-dosage digital tomosynthesis (DTS) using a multislit collimation technique

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Park, S. Y.; Kim, G. A.; Park, C. K.; Cho, H. S.; Seo, C. W.; Lee, D. Y.; Kang, S. Y.; Kim, K. S.; Lim, H. W.; Lee, H. W.; Park, J. E.; Kim, W. S.; Jeon, D. H.; Woo, T. H.

2018-04-01

In this study, we investigated an effective low-dose digital tomosynthesis (DTS) where a multislit collimator placed between the X-ray tube and the patient oscillates during projection data acquisition, partially blocking the X-ray beam to the patient thereby reducing the radiation dosage. We performed a simulation using the proposed DTS with two sets of multislit collimators both having a 50% duty cycle and investigated the image characteristics to demonstrate the feasibility of this proposed approach. In the simulation, all projections were taken at a tomographic angle of θ = ± 50° and an angle step of Δθ =2°. We utilized an iterative algorithm based on a compressed-sensing (CS) scheme for more accurate DTS reconstruction. Using the proposed DTS, we successfully obtained CS-reconstructed DTS images with no bright-band artifacts around the multislit edges of the collimator, thus maintaining the image quality. Therefore, the use of multislit collimation in current real-world DTS systems can reduce the radiation dosage to patients.

Prediction of required ozone dosage for pilot recirculating aquaculture systems based on laboratory studies

DEFF Research Database (Denmark)

Spiliotopoulou, Aikaterini; Rojas-Tirado, Paula Andrea; Kaarsholm, Kamilla Marie Speht

2017-01-01

In recirculating aquaculture systems (RAS), the water quality changes continuously. Organic and inorganic compounds accumulates creating toxic conditions for the farmed organisms. Ozone improves water quality diminishing significantly both bacteria load and dissolved organic matter. However......, in a non-meticulously designed system, residual ozone might reach the culture tanks causing significant harm to cultured species or excess costs. The aim of the study was to predict the suitable ozone dosage in pilot RAS, for water treatment purposes, based on laboratory studies. The ozone effect on water...... quality of freshwater RAS and system’s ozone demand was investigated. Bench-scale ozonation experiments revealed the ozone demand of the system to be 180 mg O3/h. Three different ozone dosages were applied to four replicated systems with fixed feed loading (1.56 kg feed/m3 make up water). Results...

Drop-on-Demand System for Manufacturing of Melt-based Solid Oral Dosage: Effect of Critical Process Parameters on Product Quality.

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Içten, Elçin; Giridhar, Arun; Nagy, Zoltan K; Reklaitis, Gintaras V

2016-04-01

The features of a drop-on-demand-based system developed for the manufacture of melt-based pharmaceuticals have been previously reported. In this paper, a supervisory control system, which is designed to ensure reproducible production of high quality of melt-based solid oral dosages, is presented. This control system enables the production of individual dosage forms with the desired critical quality attributes: amount of active ingredient and drug morphology by monitoring and controlling critical process parameters, such as drop size and product and process temperatures. The effects of these process parameters on the final product quality are investigated, and the properties of the produced dosage forms characterized using various techniques, such as Raman spectroscopy, optical microscopy, and dissolution testing. A crystallization temperature control strategy, including controlled temperature cycles, is presented to tailor the crystallization behavior of drug deposits and to achieve consistent drug morphology. This control strategy can be used to achieve the desired bioavailability of the drug by mitigating variations in the dissolution profiles. The supervisor control strategy enables the application of the drop-on-demand system to the production of individualized dosage required for personalized drug regimens.

Genetic interactions between Shox2 and Hox genes during the regional growth and development of the mouse limb.

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Neufeld, Stanley J; Wang, Fan; Cobb, John

2014-11-01

The growth and development of the vertebrate limb relies on homeobox genes of the Hox and Shox families, with their independent mutation often giving dose-dependent effects. Here we investigate whether Shox2 and Hox genes function together during mouse limb development by modulating their relative dosage and examining the limb for nonadditive effects on growth. Using double mRNA fluorescence in situ hybridization (FISH) in single embryos, we first show that Shox2 and Hox genes have associated spatial expression dynamics, with Shox2 expression restricted to the proximal limb along with Hoxd9 and Hoxa11 expression, juxtaposing the distal expression of Hoxa13 and Hoxd13. By generating mice with all possible dosage combinations of mutant Shox2 alleles and HoxA/D cluster deletions, we then show that their coordinated proximal limb expression is critical to generate normally proportioned limb segments. These epistatic interactions tune limb length, where Shox2 underexpression enhances, and Shox2 overexpression suppresses, Hox-mutant phenotypes. Disruption of either Shox2 or Hox genes leads to a similar reduction in Runx2 expression in the developing humerus, suggesting their concerted action drives cartilage maturation during normal development. While we furthermore provide evidence that Hox gene function influences Shox2 expression, this regulation is limited in extent and is unlikely on its own to be a major explanation for their genetic interaction. Given the similar effect of human SHOX mutations on regional limb growth, Shox and Hox genes may generally function as genetic interaction partners during the growth and development of the proximal vertebrate limb. Copyright © 2014 by the Genetics Society of America.

Precise integration of inducible transcriptional elements (PrIITE) enables absolute control of gene expression

DEFF Research Database (Denmark)

Pinto, Rita; Hansen, Lars; Hintze, John

2017-01-01

to be a limitation. Here, we report that the combined use of genome editing tools and last generation Tet-On systems can resolve these issues. Our principle is based on precise integration of inducible transcriptional elements (coined PrIITE) targeted to: (i) exons of an endogenous gene of interest (GOI) and (ii......Tetracycline-based inducible systems provide powerful methods for functional studies where gene expression can be controlled. However, the lack of tight control of the inducible system, leading to leakiness and adverse effects caused by undesirable tetracycline dosage requirements, has proven......) a safe harbor locus. Using PrIITE cells harboring a GFP reporter or CDX2 transcription factor, we demonstrate discrete inducibility of gene expression with complete abrogation of leakiness. CDX2 PrIITE cells generated by this approach uncovered novel CDX2 downstream effector genes. Our results provide...

Multiway real-time PCR gene expression profiling in yeast Saccharomyces cerevisiae reveals altered transcriptional response of ADH-genes to glucose stimuli.

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Ståhlberg, Anders; Elbing, Karin; Andrade-Garda, José Manuel; Sjögreen, Björn; Forootan, Amin; Kubista, Mikael

2008-04-16

The large sensitivity, high reproducibility and essentially unlimited dynamic range of real-time PCR to measure gene expression in complex samples provides the opportunity for powerful multivariate and multiway studies of biological phenomena. In multiway studies samples are characterized by their expression profiles to monitor changes over time, effect of treatment, drug dosage etc. Here we perform a multiway study of the temporal response of four yeast Saccharomyces cerevisiae strains with different glucose uptake rates upon altered metabolic conditions. We measured the expression of 18 genes as function of time after addition of glucose to four strains of yeast grown in ethanol. The data are analyzed by matrix-augmented PCA, which is a generalization of PCA for 3-way data, and the results are confirmed by hierarchical clustering and clustering by Kohonen self-organizing map. Our approach identifies gene groups that respond similarly to the change of nutrient, and genes that behave differently in mutant strains. Of particular interest is our finding that ADH4 and ADH6 show a behavior typical of glucose-induced genes, while ADH3 and ADH5 are repressed after glucose addition. Multiway real-time PCR gene expression profiling is a powerful technique which can be utilized to characterize functions of new genes by, for example, comparing their temporal response after perturbation in different genetic variants of the studied subject. The technique also identifies genes that show perturbed expression in specific strains.

Multiway real-time PCR gene expression profiling in yeast Saccharomyces cerevisiae reveals altered transcriptional response of ADH-genes to glucose stimuli

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Andrade-Garda José

2008-04-01

Full Text Available Abstract Background The large sensitivity, high reproducibility and essentially unlimited dynamic range of real-time PCR to measure gene expression in complex samples provides the opportunity for powerful multivariate and multiway studies of biological phenomena. In multiway studies samples are characterized by their expression profiles to monitor changes over time, effect of treatment, drug dosage etc. Here we perform a multiway study of the temporal response of four yeast Saccharomyces cerevisiae strains with different glucose uptake rates upon altered metabolic conditions. Results We measured the expression of 18 genes as function of time after addition of glucose to four strains of yeast grown in ethanol. The data are analyzed by matrix-augmented PCA, which is a generalization of PCA for 3-way data, and the results are confirmed by hierarchical clustering and clustering by Kohonen self-organizing map. Our approach identifies gene groups that respond similarly to the change of nutrient, and genes that behave differently in mutant strains. Of particular interest is our finding that ADH4 and ADH6 show a behavior typical of glucose-induced genes, while ADH3 and ADH5 are repressed after glucose addition. Conclusion Multiway real-time PCR gene expression profiling is a powerful technique which can be utilized to characterize functions of new genes by, for example, comparing their temporal response after perturbation in different genetic variants of the studied subject. The technique also identifies genes that show perturbed expression in specific strains.

[National and regional market penetration rates of generic's high dosage buprenorphine: its evolution from 2006 to 2008, using reimbursed drug database].

Science.gov (United States)

Boczek, Christelle; Frauger, Elisabeth; Micallef, Joëlle; Allaria-Lapierre, Véronique; Reggio, Patrick; Sciortino, Vincent

2012-01-01

To assess the national market penetration rate (PR) of generic high-dosage buprenorphine (HDB) in 2008 and its evolution since their marketing (2006), and making a point for each dosage and at regional level. Retrospective study over data using national and regional health reimbursement database over three years (2006-2008). In 2008, the generic HDB's national MPR was 31%. The PR for each dosage were 45% for 0.4 mg, 36% for 2 mg and 19% for 8 mg. The (PR) based on Defined Daily Dose (DDD) was 23% in 2008, 15% in 2007 and 4% in 2006. In 2008, at the regional level, disparities were observed in the adjusted penetration rate from 15% in Île de France to 39% in Champagne Ardennes Lorraine. The national PR of generic HDB has increased. There are differences in MPR in terms of dosage and area. However, this PR is still low (in 2008, 82% of the delivered drugs are generics). © 2012 Société Française de Pharmacologie et de Thérapeutique.

The influences of adrenaline dosing frequency and dosage on outcomes of adult in-hospital cardiac arrest: A retrospective cohort study.

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Wang, Chih-Hung; Huang, Chien-Hua; Chang, Wei-Tien; Tsai, Min-Shan; Yu, Ping-Hsun; Wu, Yen-Wen; Hung, Kuan-Yu; Chen, Wen-Jone

2016-06-01

To investigate the influence of dosing frequency and dosage of adrenaline on outcomes of cardiopulmonary resuscitation (CPR). We conducted a retrospective observational study in a single medical centre and included adult patients who had suffered an in-hospital cardiac arrest between 2006 and 2012. We used multivariable logistic regression analysis to evaluate the associations between independent variables and outcomes. Adrenaline average dosing frequency was calculated as the total dosage of adrenaline administered during CPR divided by the duration of CPR. Body weight (BW) was analysed as an interaction term to investigate the effect of adrenaline dosage on outcomes. Favourable neurological outcome was defined as a score of 1 or 2 on the Cerebral Performance Category scale at hospital discharge. We included 896 patients in the analysis. After adjusting for multiple confounding factors, including CPR duration, the results indicated that higher adrenaline dosing frequency was associated with lower rates of survival (odds ratio (OR): 0.05, 95% confidence interval (CI): 0.01-0.23) and favourable neurological outcome at hospital discharge (OR: 0.02, 95% CI: 0.002-0.16). A significant interaction was noted between total adrenaline dosage and BW, which indicated that, with the same adrenaline dosage, the outcomes for patients with BW≥82.5kg would be worse than those for patients with lower BW. Higher adrenaline average dosing frequency may be associated with worse outcomes after CPR. Besides, according to current recommendations, patients with BW above 82.5kg may not receive adequate dose of adrenaline. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

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

Science.gov (United States)

2011-01-20

.... FDA-2010-N-0002] Implantation or Injectable Dosage Form New Animal Drugs; Oxytetracycline and Flunixin... combination drug injectable solution containing oxytetracycline and flunixin meglumine in cattle. [[Page 3489... veterinary prescription use of HEXASOL (oxytetracycline and flunixin meglumine) Injection for the treatment...

Human ETS2 gene on chromosome 21 is not rearranged in Alzheimer disease

International Nuclear Information System (INIS)

Sacchi, N.; Nalbantoglu, J.; Sergovich, F.R.; Papas, T.S.

1988-01-01

The human ETS2 gene, a member of the ETS gene family, with sequence homology with the retroviral ets sequence of the avian erythroblastosis retrovirus E26 is located on chromosome 21. Molecular genetic analysis of Down syndrome (DS) patients with partial trisomy 21 allowed us to reinforce the supposition that ETS2 may be a gene of the minimal DS genetic region. It was originally proposed that a duplication of a portion of the DS region represents the genetic basis of Alzheimer disease, a condition associated also with DS. No evidence of either rearrangements or duplications of ETS2 could be detected in DNA from fibroblasts and brain tissue of Alzheimer disease patients with either the sporadic or the familiar form of the disease. Thus, an altered ETS2 gene dosage does not seem to be a genetic cause or component of Alzheimer disease

Dropwise additive manufacturing of pharmaceutical products for melt-based dosage forms.

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Içten, Elçin; Giridhar, Arun; Taylor, Lynne S; Nagy, Zoltan K; Reklaitis, Gintaras V

2015-05-01

The US Food and Drug Administration introduced the quality by design approach and process analytical technology guidance to encourage innovation and efficiency in pharmaceutical development, manufacturing, and quality assurance. As part of this renewed emphasis on the improvement of manufacturing, the pharmaceutical industry has begun to develop more efficient production processes with more intensive use of online measurement and sensing, real-time quality control, and process control tools. Here, we present dropwise additive manufacturing of pharmaceutical products (DAMPP) as an alternative to conventional pharmaceutical manufacturing methods. This mini-manufacturing process for the production of pharmaceuticals utilizes drop on demand printing technology for automated and controlled deposition of melt-based formulations onto edible substrates. The advantages of drop-on-demand technology, including reproducible production of small droplets, adjustable drop sizing, high placement accuracy, and flexible use of different formulations, enable production of individualized dosing even for low-dose and high-potency drugs. In this work, DAMPP is used to produce solid oral dosage forms from hot melts of an active pharmaceutical ingredient and a polymer. The dosage forms are analyzed to show the reproducibility of dosing and the dissolution behavior of different formulations. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

Biowaiver Monographs for Immediate-Release Solid Oral Dosage Forms: Folic Acid.

Science.gov (United States)

Hofsäss, Martin A; Souza, Jacqueline de; Silva-Barcellos, Neila M; Bellavinha, Karime R; Abrahamsson, Bertil; Cristofoletti, Rodrigo; Groot, D W; Parr, Alan; Langguth, Peter; Polli, James E; Shah, Vinod P; Tajiri, Tomokazu; Mehta, Mehul U; Dressman, Jennifer B

2017-12-01

This work presents a review of literature and experimental data relevant to the possibility of waiving pharmacokinetic bioequivalence studies in human volunteers for approval of immediate-release solid oral pharmaceutical forms containing folic acid as the single active pharmaceutical ingredient. For dosage forms containing 5 mg folic acid, the highest dose strength on the World Health Organization Essential Medicines List, the dose/solubility ratio calculated from solubility studies was higher than 250 mL, corresponding to a classification as "not highly soluble." Small, physiological doses of folic acid (≤320 μg) seem to be absorbed completely via active transport, but permeability data for higher doses of 1-5 mg are inconclusive. Following a conservative approach, folic acid is classified as a Biopharmaceutics Classification System class IV compound until more reliable data become available. Commensurate with its solubility characteristics, the results of dissolution studies indicated that none of the folic acid products evaluated showed rapid dissolution in media at pH 1.2 or 4.5. Therefore, according to the current criteria of the Biopharmaceutics Classification System, the biowaiver approval procedure cannot be recommended for immediate-release solid oral dosage forms containing folic acid. Copyright © 2017 American Pharmacists Association®. All rights reserved.

Prediction of dosage-based parameters from the puff dispersion of airborne materials in urban environments using the CFD-RANS methodology

Science.gov (United States)

Efthimiou, G. C.; Andronopoulos, S.; Bartzis, J. G.

2018-02-01

One of the key issues of recent research on the dispersion inside complex urban environments is the ability to predict dosage-based parameters from the puff release of an airborne material from a point source in the atmospheric boundary layer inside the built-up area. The present work addresses the question of whether the computational fluid dynamics (CFD)-Reynolds-averaged Navier-Stokes (RANS) methodology can be used to predict ensemble-average dosage-based parameters that are related with the puff dispersion. RANS simulations with the ADREA-HF code were, therefore, performed, where a single puff was released in each case. The present method is validated against the data sets from two wind-tunnel experiments. In each experiment, more than 200 puffs were released from which ensemble-averaged dosage-based parameters were calculated and compared to the model's predictions. The performance of the model was evaluated using scatter plots and three validation metrics: fractional bias, normalized mean square error, and factor of two. The model presented a better performance for the temporal parameters (i.e., ensemble-average times of puff arrival, peak, leaving, duration, ascent, and descent) than for the ensemble-average dosage and peak concentration. The majority of the obtained values of validation metrics were inside established acceptance limits. Based on the obtained model performance indices, the CFD-RANS methodology as implemented in the code ADREA-HF is able to predict the ensemble-average temporal quantities related to transient emissions of airborne material in urban areas within the range of the model performance acceptance criteria established in the literature. The CFD-RANS methodology as implemented in the code ADREA-HF is also able to predict the ensemble-average dosage, but the dosage results should be treated with some caution; as in one case, the observed ensemble-average dosage was under-estimated slightly more than the acceptance criteria. Ensemble

Real-time PCR quantification of human complement C4A and C4B genes

Directory of Open Access Journals (Sweden)

Fust George

2006-01-01

Full Text Available Abstract Background The fourth component of human complement (C4, an essential factor of the innate immunity, is represented as two isoforms (C4A and C4B in the genome. Although these genes differ only in 5 nucleotides, the encoded C4A and C4B proteins are functionally different. Based on phenotypic determination, unbalanced production of C4A and C4B is associated with several diseases, such as systemic lupus erythematosus, type 1 diabetes, several autoimmune diseases, moreover with higher morbidity and mortality of myocardial infarction and increased susceptibility for bacterial infections. Despite of this major clinical relevance, only low throughput, time and labor intensive methods have been used so far for the quantification of C4A and C4B genes. Results A novel quantitative real-time PCR (qPCR technique was developed for rapid and accurate quantification of the C4A and C4B genes applying a duplex, TaqMan based methodology. The reliable, single-step analysis provides the determination of the copy number of the C4A and C4B genes applying a wide range of DNA template concentration (0.3–300 ng genomic DNA. The developed qPCR was applied to determine C4A and C4B gene dosages in a healthy Hungarian population (N = 118. The obtained data were compared to the results of an earlier study of the same population. Moreover a set of 33 samples were analyzed by two independent methods. No significant difference was observed between the gene dosages determined by the employed techniques demonstrating the reliability of the novel qPCR methodology. A Microsoft Excel worksheet and a DOS executable are also provided for simple and automated evaluation of the measured data. Conclusion This report describes a novel real-time PCR method for single-step quantification of C4A and C4B genes. The developed technique could facilitate studies investigating disease association of different C4 isotypes.

Heritable and lineage-specific gene knockdown in zebrafish embryo.

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Mei Dong

Full Text Available BACKGROUND: Reduced expression of developmentally important genes and tumor suppressors due to haploinsufficiency or epigenetic suppression has been shown to contribute to the pathogenesis of various malignancies. However, methodology that allows spatio-temporally knockdown of gene expression in various model organisms such as zebrafish has not been well established, which largely limits the potential of zebrafish as a vertebrate model of human malignant disorders. PRINCIPAL FINDING: Here, we report that multiple copies of small hairpin RNA (shRNA are expressed from a single transcript that mimics the natural microRNA-30e precursor (mir-shRNA. The mir-shRNA, when microinjected into zebrafish embryos, induced an efficient knockdown of two developmentally essential genes chordin and alpha-catenin in a dose-controllable fashion. Furthermore, we designed a novel cassette vector to simultaneously express an intronic mir-shRNA and a chimeric red fluorescent protein driven by lineage-specific promoter, which efficiently reduced the expression of a chromosomally integrated reporter gene and an endogenously expressed gata-1 gene in the developing erythroid progenitors and hemangioblasts, respectively. SIGNIFICANCE: This methodology provides an invaluable tool to knockdown developmental important genes in a tissue-specific manner or to establish animal models, in which the gene dosage is critically important in the pathogenesis of human disorders. The strategy should be also applicable to other model organisms.

Transmission microscopy of unmodified biological materials: comparative radiation dosages with electrons and ultrasoft X-ray photons

International Nuclear Information System (INIS)

Sayre, D.; Feder, R.; Spiller, E.; Kirz, J.; Kim, D.M.

1977-01-01

The minimum radiation dosage in a specimen consistent with transmission microscopy at resolution d and specimen thickness t is calculated for model specimens resembling biological materials in their natural state. The calculations cover 10 4 -10 7 eV electrons and 1.3-90 A photons in a number of microscopy modes. The results indicate that over a considerable part of the (t,d)-plane transmission microscopy on such specimens can be carried out at lower dosage with photons than with electrons. Estimates of the maximum resolutions obtainable with electrons and photons, consistent with structural survival of the specimen, are obtained, as are data on optimal operating conditions for microscopy with the two particles

Assessment of Digoxin-Specific Fab Fragment Dosages in Digoxin Poisoning.

Science.gov (United States)

Nordt, Sean Patrick; Clark, Richard F; Machado, Carol; Cantrell, F Lee

2016-01-01

Digoxin poisoning still remains a common cause of morbidity and mortality. Fortunately, digoxin-specific Fab fragments are commercially available as an antidote. However, these Fab fragments are several thousand dollars per vial. There is a standardized formula to calculate appropriate Fab fragment dosage based on the serum digoxin concentration. This can greatly reduce the amount of Fab fragment administered. There is also an empiric dosing guideline recommending 6-10 vials be given; however, this may result in higher amounts of Fab fragments being administered than required. We performed this study to assess the amounts of digoxin-specific Fab fragments administered in the treatment of digoxin poisonings recorded in a poison control system database from January 1, 2000, to December 31, 2009, in which digoxin serum concentrations were available. This was a retrospective study of 278 patients, 107 with acute poisonings (group A) and 171 following chronic poisoning (group B). In group A, the calculated Fab dose was higher than the calculated dose based on available concentrations in 39 (36%) of group A and 15 (9%) of group B patients. The average wholesale price cost of the excessive dosages ranged from $4818 to as high as $50,589 per patient. Our data suggests that clinician education on digoxin poisoning and the use of the standardized formula to calculate the Fab dose may decrease over utilization and decrease costs associated with the administration of digoxin-specific Fab fragments in the treatment of digoxin poisonings.

Identification and characterization of novel mutations of the major Fanconi anemia gene FANCA in the Japanese population.

Science.gov (United States)

Yagasaki, Hiroshi; Hamanoue, Satoshi; Oda, Tsukasa; Nakahata, Tatsutoshi; Asano, Shigetaka; Yamashita, Takayuki

2004-12-01

Fanconi anemia (FA) is a rare autosomal recessive disorder of hematopoiesis, with at least 11 complementation groups. FANCA, a gene for group A, accounts for the majority of FA patients. Previous studies of FANCA mutations revealed high allelic heterogeneity, frequent occurrence of large deletions, and interpopulation differences. However, systematic mutational analysis, including gene dosage assay to detect large deletions, has not been documented for Asian populations. A newly developed TaqMan quantitative PCR-based gene dosage assay, combined with sequencing of exons and cDNA fragments, allowed for detection of 48 mutant alleles of FANCA in 27 (77%) of 35 unrelated Japanese FA families with no detectable mutations in FANCC or FANCG. We identified 29 different mutations (21 nucleotide substitutions or small deletions/insertions and eight large deletions), at least 20 of which were novel. The FANCA mutational spectrum of the Japanese was different from that of other ethnic groups so far studied. This is the largest scale of mutation analysis of FANCA in the Japanese population. Characterization of these mutations provided new information regarding the mutagenesis mechanisms and structure-function relationship of FANCA. Specifically, our data suggest that diverse mechanisms including nonhomologous recombination as well as Alu-mediated homologous recombination are involved in the generation of large deletions in FANCA. Copyright 2004 Wiley-Liss, Inc.

Influence of prenatal EGCG treatment and Dyrk1a dosage reduction on craniofacial features associated with Down syndrome.

Science.gov (United States)

McElyea, Samantha D; Starbuck, John M; Tumbleson-Brink, Danika M; Harrington, Emily; Blazek, Joshua D; Ghoneima, Ahmed; Kula, Katherine; Roper, Randall J

2016-11-15

Trisomy 21 (Ts21) affects craniofacial precursors in individuals with Down syndrome (DS). The resultant craniofacial features in all individuals with Ts21 may significantly affect breathing, eating and speaking. Using mouse models of DS, we have traced the origin of DS-associated craniofacial abnormalities to deficiencies in neural crest cell (NCC) craniofacial precursors early in development. Hypothetically, three copies of Dyrk1a (dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 1A), a trisomic gene found in most humans with DS and mouse models of DS, may significantly affect craniofacial structure. We hypothesized that we could improve DS-related craniofacial abnormalities in mouse models using a Dyrk1a inhibitor or by normalizing Dyrk1a gene dosage. In vitro and in vivo treatment with Epigallocatechin-3-gallate (EGCG), a Dyrk1a inhibitor, modulated trisomic NCC deficiencies at embryonic time points. Furthermore, prenatal EGCG treatment normalized some craniofacial phenotypes, including cranial vault in adult Ts65Dn mice. Normalization of Dyrk1a copy number in an otherwise trisomic Ts65Dn mice normalized many dimensions of the cranial vault, but did not correct all craniofacial anatomy. These data underscore the complexity of the gene–phenotype relationship in trisomy and suggest that changes in Dyrk1a expression play an important role in morphogenesis and growth of the cranial vault. These results suggest that a temporally specific prenatal therapy may be an effective way to ameliorate some craniofacial anatomical changes associated with DS.

Design of a gastroretentive mucoadhesive dosage form of furosemide for controlled release

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Sharad S. Darandale

2012-10-01

Full Text Available The aim of the present study was to develop and characterize a gastroretentive dosage form suitable for controlled drug release. It consists of a drug loaded polymeric film made up of a bilayer of immediate (IR and controlled release (CR layers folded into a hard gelatin capsule. Gastroretention results from unfolding and swelling of the film and its bioadhesion to the gastric mucosa. Furosemide, a drug with a narrow absorption window, was selected as the model drug. Inclusion of hydroxypropyl β-cyclodextrin in both layers and Carbopol® 971P NF in the CR layer of the bilayer film resulted in optimum drug release, bioadhesion and mechanical properties. The film with zig-zag folding in the capsule was shown to unfold and swell under acidic conditions and provide IR of drug over 1 h and CR for up to 12 h in acidic medium. X-ray diffraction, differential scanning calorimetry and scanning electron microscopy revealed uniform dispersion of furosemide in the polymeric matrices. The results indicate the dosage form is gastroretentive and can provide controlled release of drugs with narrow therapeutic windows.

Semi-quantitative prediction of a multiple API solid dosage form with a combination of vibrational spectroscopy methods.

Science.gov (United States)

Hertrampf, A; Sousa, R M; Menezes, J C; Herdling, T

2016-05-30

Quality control (QC) in the pharmaceutical industry is a key activity in ensuring medicines have the required quality, safety and efficacy for their intended use. QC departments at pharmaceutical companies are responsible for all release testing of final products but also all incoming raw materials. Near-infrared spectroscopy (NIRS) and Raman spectroscopy are important techniques for fast and accurate identification and qualification of pharmaceutical samples. Tablets containing two different active pharmaceutical ingredients (API) [bisoprolol, hydrochlorothiazide] in different commercially available dosages were analysed using Raman- and NIR Spectroscopy. The goal was to define multivariate models based on each vibrational spectroscopy to discriminate between different dosages (identity) and predict their dosage (semi-quantitative). Furthermore the combination of spectroscopic techniques was investigated. Therefore, two different multiblock techniques based on PLS have been applied: multiblock PLS (MB-PLS) and sequential-orthogonalised PLS (SO-PLS). NIRS showed better results compared to Raman spectroscopy for both identification and quantitation. The multiblock techniques investigated showed that each spectroscopy contains information not present or captured with the other spectroscopic technique, thus demonstrating that there is a potential benefit in their combined use for both identification and quantitation purposes. Copyright © 2016 Elsevier B.V. All rights reserved.

Modeled dosage-response relationship on the net photosynthetic rate for the sensitivity to acid rain of 21 plant species.

Science.gov (United States)

Deng, Shihuai; Gou, Shuzhen; Sun, Baiye; Lv, Wenlin; Li, Yuanwei; Peng, Hong; Xiao, Hong; Yang, Gang; Wang, Yingjun

2012-08-01

This study investigated the sensitivity of plant species to acid rain based on the modeled dosage-response relationship on the net photosynthetic rate (P (N)) of 21 types of plant species, subjected to the exposure of simulated acid rain (SAR) for 5 times during a period of 50 days. Variable responses of P (N) to SAR occurred depending on the type of plant. A majority (13 species) of the dosage-response relationship could be described by an S-shaped curve and be fitted with the Boltzmann model. Model fitting allowed quantitative evaluation of the dosage-response relationship and an accurate estimation of the EC(10), termed as the pH of the acid rain resulting in a P (N) 10 % lower than the reference value. The top 9 species (Camellia sasanqua, Cinnamomum camphora, etc. EC(10) ≤ 3.0) are highly endurable to very acid rain. The rare, relict plant Metasequoia glyptostroboides was the most sensitive species (EC(10) = 5.1) recommended for protection.

Serial Expression Analysis: a web tool for the analysis of serial gene expression data

Science.gov (United States)

Nueda, Maria José; Carbonell, José; Medina, Ignacio; Dopazo, Joaquín; Conesa, Ana

2010-01-01

Serial transcriptomics experiments investigate the dynamics of gene expression changes associated with a quantitative variable such as time or dosage. The statistical analysis of these data implies the study of global and gene-specific expression trends, the identification of significant serial changes, the comparison of expression profiles and the assessment of transcriptional changes in terms of cellular processes. We have created the SEA (Serial Expression Analysis) suite to provide a complete web-based resource for the analysis of serial transcriptomics data. SEA offers five different algorithms based on univariate, multivariate and functional profiling strategies framed within a user-friendly interface and a project-oriented architecture to facilitate the analysis of serial gene expression data sets from different perspectives. SEA is available at sea.bioinfo.cipf.es. PMID:20525784

High gonadotropin dosage does not affect euploidy and pregnancy rates in IVF PGS cycles with single embryo transfer.

Science.gov (United States)

Barash, Oleksii O; Hinckley, Mary D; Rosenbluth, Evan M; Ivani, Kristen A; Weckstein, Louis N

2017-11-01

Does high gonadotropin dosage affect euploidy and pregnancy rates in PGS cycles with single embryo transfer? High gonadotropin dosage does NOT affect euploidy and pregnancy rates in PGS cycles with single embryo transfer. PGS has been proven to be the most effective and reliable method for embryo selection in IVF cycles. Euploidy and blastulation rates decrease significantly with advancing maternal age. In order to recruit an adequate number of follicles, the average dosage of gonadotropins administered during controlled ovarian stimulation in IVF cycles often increases significantly with advancing maternal age. A retrospective study of SNP (Single Nucleotide Polymorphism) PGS outcome data from blastocysts biopsied on day 5 or day 6 was conducted to identify differences in euploidy and clinical pregnancy rates. Seven hundred and ninety four cycles of IVF treatment with PGS between January 2013 and January 2017 followed by 651 frozen embryo transfers were included in the study (506 patients, maternal age (y.o.) - 37.2 ± 4.31). A total of 4034 embryos were analyzed (5.1 ± 3.76 per case) for euploidy status. All embryos were vitrified after biopsy, and selected embryos were subsequently thawed for a hormone replacement frozen embryo transfer cycle. All cycles were analyzed by total gonadotropin dosage (5000 IU), by number of eggs retrieved (1-5, 5-10, 10-15 and >15 eggs) and patient's age (cycles) euploidy rates ranged from 62.3% (cycle) to 67.5% (>5000 IU were used in the IVF cycle) (OR = 0.862, 95% CI 0.687-1.082, P = 0.2) and from 69.5% (1-5 eggs retrieved) to 60.0% (>15 eggs retrieved) (OR = 0.658, 95% CI 0.405-1.071, P = 0.09). Similar data were obtained in the oldest group of patients (≥41 y.o. - 189 IVF cycles): euploidy rates ranged from 30.7 to 26.4% (OR = 0.811, 95% CI 0.452-1.454, P = 0.481) when analyzed by total dosage of gonadotropins used in the IVF cycle and from 40.0 to 30.7% (OR = 0.531, 95% CI 0.204-1.384, P = 0.19), when assessed by the total

Sequence-specific targeting of dosage compensation in Drosophila favors an active chromatin context.

Directory of Open Access Journals (Sweden)

Artyom A Alekseyenko

Full Text Available The Drosophila MSL complex mediates dosage compensation by increasing transcription of the single X chromosome in males approximately two-fold. This is accomplished through recognition of the X chromosome and subsequent acetylation of histone H4K16 on X-linked genes. Initial binding to the X is thought to occur at "entry sites" that contain a consensus sequence motif ("MSL recognition element" or MRE. However, this motif is only ∼2 fold enriched on X, and only a fraction of the motifs on X are initially targeted. Here we ask whether chromatin context could distinguish between utilized and non-utilized copies of the motif, by comparing their relative enrichment for histone modifications and chromosomal proteins mapped in the modENCODE project. Through a comparative analysis of the chromatin features in male S2 cells (which contain MSL complex and female Kc cells (which lack the complex, we find that the presence of active chromatin modifications, together with an elevated local GC content in the surrounding sequences, has strong predictive value for functional MSL entry sites, independent of MSL binding. We tested these sites for function in Kc cells by RNAi knockdown of Sxl, resulting in induction of MSL complex. We show that ectopic MSL expression in Kc cells leads to H4K16 acetylation around these sites and a relative increase in X chromosome transcription. Collectively, our results support a model in which a pre-existing active chromatin environment, coincident with H3K36me3, contributes to MSL entry site selection. The consequences of MSL targeting of the male X chromosome include increase in nucleosome lability, enrichment for H4K16 acetylation and JIL-1 kinase, and depletion of linker histone H1 on active X-linked genes. Our analysis can serve as a model for identifying chromatin and local sequence features that may contribute to selection of functional protein binding sites in the genome.

Phenotypic Consequences of Altering the Copy Number of abiA, a Gene Responsible for Aborting Bacteriophage Infections in Lactococcus lactis†

OpenAIRE

Dinsmore, Polly K.; Klaenhammer, Todd R.

1994-01-01

The abiA gene (formerly hsp) encodes an abortive phage infection mechanism which inhibits phage DNA replication. To analyze the effects of varying the abiA gene dosage on bacteriophage resistance in Lactococcus lactis, various genetic constructions were made. An IS946-based integration vector, pTRK75, was used to integrate a single copy of abiA into the chromosomes of two lactococcal strains, MG1363 and NCK203. In both strains, a single copy of abiA did not confer any significant phage resist...

75 FR 26647 - Ophthalmic and Topical Dosage Form New Animal Drugs; Ivermectin Topical Solution

Science.gov (United States)

2010-05-12

.... FDA-2010-N-0002] Ophthalmic and Topical Dosage Form New Animal Drugs; Ivermectin Topical Solution... are treated with a topical solution of ivermectin. DATES: This rule is effective May 12, 2010. FOR... ANADA 200-340 for PRIVERMECTIN (ivermectin), a topical solution used on cattle to control infestations...

The effect of two dosage of BCAA supplementation on wrestlers’ serum indexes on cellular injury

Directory of Open Access Journals (Sweden)

Ramin Amirsasan

2012-01-01

Full Text Available Background: A few studies were done to examine the effect of different dosage of branched-chain amino acid (BCAA supplementation on serum indexes of muscle injury in wrestlers. The purpose of this research was to compare the effects of two dosage of branched-chain amino acid supplementation on muscle serumic damage indexes after heavy resistance exercise in wrestlers.Materials and Method: Twenty-nine young wrestlers were randomly selected and divided into three groups. All subjects were participated in heavy resistance exercise (3 sets, 10 repetitions, 80% 1RM. The BCAA was given at doses of 210 and 450 mg/kg for supplemental groups 1 and 2 respectively, 30 minutes before and after to exercise test and dextrin was given at dose of 210 mg/kg for control group. To identify enzymes activity (IU/L, venous blood samples were obtained 30 min prior to exercise and at 24 and 48 hrs after exercise. Data were statistically analyzed using ANOVA with repeated measures and Bonfferoni post hoc test (p≥ 0.05.Results: Based on this study results, CPK, LDH, CPKMB activity were significantly increased (p<0.05 in all groups. CPK, LDH, CPKMB indexes having the highest activity in the control group, but there were no significant differences between all groups. Conclusion: These results provide evidence that the use of two different dosage of BCAA could not decrease muscle damage associated with heavy resistance exercise

Formulation and process considerations affecting the stability of solid dosage forms formulated with methacrylate copolymers.

Science.gov (United States)

Petereit, H U; Weisbrod, W

1999-01-01

General considerations concerning the stability of coated dosage forms are discussed, in order to avoid predictable interactions which may cause long-term stability problems. As polymers themselves maintain a high chemical stability and a low reactivity, instability phenomena mainly have to be explained by interactions of low molecular weight substances or physical changes. Possible interactions of functional groups can be predicted easily and insulating subcoates are proper countermeasures. Impurities, remaining in the polymeric material from the manufacturing process, may accelerate the hydrolysis of sensitive drugs. Instabilities of coated dosage forms are mainly based on physical interactions, caused by improper formulations of coating suspensions (i.e. plasticizers or pigments) or the film coating process. Residual moisture or solvents, probably enclosed in the core and migrating over time, may increase the permeability of coatings, due to plasticizing effects. The functionality of coatings from aqueous dispersions is linked to coalescence of latex particles. Thus any incomplete film formation, caused by too high or too low coating temperatures, may result in high permeable coatings. During storage, preferably under stress conditions this process will continue and thus change the release profile. Therefore bed temperatures of 10-20 degrees C above MFT must ensure the formation of homogeneous polymer layers during the coating process. Stability test procedures and packaging materials also need to be adapted to the physicochemical properties of the dosage form, in order to get meaningful results in stability tests.

Historical and Clinical Experiences of Gene Therapy  for Solid Cancers in China

Directory of Open Access Journals (Sweden)

Bo Li

2017-02-01

Full Text Available Based on the theoretical and clinical development of modern medicines, gene therapy has been a promising treatment strategy for cancer and other diseases. The practice of gene therapy is nearly 27 years old, since the first authorized gene transfer study took place at the National Institute of Health in 1989. However, gene therapy was not readily adopted worldwide, until recently. Several gene therapy clinical trials have been carried out in China since 1998, and medical research in China has flourished. In this report, we review the history of gene therapy in China, focusing on treatment protocol, the administration cycle, dosage calculation, and the evaluation of therapeutic effects, in order to provide more information for the additional development of this promising treatment strategy.

Genome-Wide Association Study with Sequence Variants Identifies Candidate Genes for Mastitis Resistance in Dairy Cattle

DEFF Research Database (Denmark)

Sahana, Goutam; Guldbrandtsen, Bernt; Bendixen, Christian

Six genomic regions affecting clinical mastitis were identified through a GWAS study with imputed BovineHD chip genotype data in the Nordic Holstein cattle population. The association analyses were carried out using a SNP-by-SNP analysis by fitting the regression of allele dosage and a polygenic...... Effect Predictor (VEP) vers. 2.6 using ENSEMBL vers. 67 databases. Candidate polymorphisms affecting clinical mastitis were selected based on their association with the traits and functional annotations. A strong positional candidate gene for mastitis resistance on chromosome-6 is the NPFFR2 which...... Factor Receptor Alpha (LIFR) emerged as a strong candidate gene for mastitis resistance. The LIFR gene is involved in acute phase response and is expressed in saliva and mammary gland....

A cluster-analytic profiling of heroin-dependent patients based on level, clinical adequacy, and patient-desired adjustment of buprenorphine dosage during buprenorphine-naloxone maintenance treatment in sixteen Spanish centers.

Science.gov (United States)

Alcaraz, Saul; González-Saiz, Francisco; Trujols, Joan; Vergara-Moragues, Esperanza; Siñol, Núria; Pérez de Los Cobos, José

2018-06-01

Buprenorphine dosage is a crucial factor influencing outcomes of buprenorphine treatment for heroin use disorders. Therefore, the aim of the present study is to identify naturally occurring profiles of heroin-dependent patients regarding individualized management of buprenorphine dosage in clinical practice of buprenorphine-naloxone maintenance treatment. 316 patients receiving buprenorphine-naloxone maintenance treatment were surveyed at 16 Spanish centers during the stabilization phase of this treatment. Patients were grouped using cluster analysis based on three key indicators of buprenorphine dosage management: dose, adequacy according to physician, and adjustment according to patient. The clusters obtained were compared regarding different facets of patient clinical condition. Four clusters were identified and labeled as follows (buprenorphine average dose and percentage of participants in each cluster are given in brackets): "Clinically Adequate and Adjusted to Patient Desired Low Dosage" (2.60 mg/d, 37.05%); "Clinically Adequate and Adjusted to Patient Desired High Dosage" (10.71 mg/d, 29.18%); "Clinically Adequate and Patient Desired Reduction of Low Dosage" (3.38 mg/d, 20.0%); and "Clinically Inadequate and Adjusted to Patient Desired Moderate Dosage" (7.55 mg/d, 13.77%). Compared to patients from the other three clusters, participants in the latter cluster reported more frequent use of heroin and cocaine during last week, lower satisfaction with buprenorphine-naloxone as a medication, higher prevalence of buprenorphine-naloxone adverse effects and poorer psychological adjustment. Our results show notable differences between clusters of heroin-dependent patients regarding buprenorphine dosage management. We also identified a group of patients receiving clinically inadequate buprenorphine dosage, which was related to poorer clinical condition. Copyright © 2018 Elsevier B.V. All rights reserved.

Spectrographic determination of chlorine and fluorine; Dosage du chlore et du fluor par spectrographie d'emission en atmosphere inerte

Energy Technology Data Exchange (ETDEWEB)

Contamin, G [Commissariat a l' Energie Atomique, Grenoble (France). Centre d' Etudes Nucleaires

1965-04-01

Experimental conditions have been investigated in order to obtain the highest sensitivity in spectrographic determination of chlorine and fluorine using the Fassel method of excitation in an inert atmosphere. The influence of the nature of the atmosphere, of the discharge conditions and of the matrix material has been investigated. The following results have been established: 1. chlorine determination is definitely possible: a working curve has been drawn between 10 {mu}g and 100 {mu}g, the detection limit being around 5 {mu}g; 2. fluorine determination is not satisfactory: the detection limit is still of the order of 80 {mu}g. The best operating conditions have been defined for both elements. (author) [French] Nous avons recherche quelles etaient les conditions permettant d'obtenir la meilleure sensibilite dans le dosage spectrographique du chlore et du fluor par la methode d'excitation en atmosphere inerte (methode de Fassel). Nous avons etudie l'influence de l'atmosphere gazeuse, des conditions de la decharge et du materiau de pastillage. Les points suivants ont ete etablis: 1. le dosage du chlore est possible: une courbe de dosage a ete tracee entre 10 {mu}g et 100 {mu}g et la limite de detection est de l'ordre de 5 {mu}g; 2. le dosage du fluor n'est pas satisfaisant: la limite de detection obtenue etant encore de l'ordre de 80 {mu}g. Les conditions operatoires ont ete precisees pour ces deux elements. (auteur)

Quantification of expression and methylation of the Igf2r imprinted gene in segmental trisomic mouse model

Czech Academy of Sciences Publication Activity Database

Vacík, Tomáš; Forejt, Jiří

2003-01-01

Roč. 82, - (2003), s. 261-268 ISSN 0888-7543 R&D Projects: GA MŠk LN00A079; GA ČR GV204/98/K015 Grant - others:HHMI(US) 555000306 Institutional research plan: CEZ:AV0Z5052915 Keywords : Genomic imprinting * dosage-sensitive genes * Ts43H segmental trisomy of chromosome 17 Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.488, year: 2003

Role of SeqA and Dam in Escherichia coli gene expression: A global/microarray analysis

DEFF Research Database (Denmark)

Løbner-Olesen, Anders; Marinus, M.G.; Hansen, Flemming G.

2003-01-01

High-density oligonucleotide arrays were used to monitor global transcription patterns in Escherichia coli with various levels of Dam and SeqA proteins. Cells lacking Dam methyltransferase showed a modest increase in transcription of the genes belonging to the SOS regulon. Bacteria devoid...... of the SeqA protein, which preferentially binds hemimethylated DNA, were found to have a transcriptional profile almost identical to WT bacteria overexpressing Dam methyltransferase. The latter two strains differed from WT in two ways. First, the origin proximal genes were transcribed with increased...... frequency due to increased gene dosage. Second, chromosomal domains of high transcriptional activity alternate with regions of low activity, and our results indicate that the activity in each domain is modulated in the same way by SeqA deficiency or Dam overproduction. We suggest that the methylation status...

What is the optimum maximal gonadotropin dosage used in microdose flare-up cycles in poor responders?

Science.gov (United States)

Berkkanoglu, Murat; Ozgur, Kemal

2010-07-01

To find out the optimum maximal dosage of recombinant follicle stimulating hormone (rFSH) in microdose gonadotropin-releasing hormone analog (GnRH-a) flare cycles in poor responders. Prospective randomized study. Private infertility clinic. A total of 119 women were taken into the study. The study group underwent a microdose protocol with a GnRH-agonist followed by rFSH administration. On the third day of GnRH-a administration, 119 patients were randomized in three groups to receive daily fixed doses of 300 IU of rFSH (group A, n = 38), or 450 IU of rFSH (group B, n = 39), or 600 IU of rFSH (group C, n = 42). Peak E(2) levels, days of stimulation with rFSH, total rFSH dosage, total number of oocytes retrieved, M2 oocytes retrieved, total number of embryos, number of embryos transferred, number of Grade-1 embryos transferred, clinical pregnancy rate (positive fetal cardiac activity), and cancellation rates of stimulation and embryo transfer. Clinical pregnancy rates were 13.1%, 15.3%, and 16.1% for group A, group B, and group C, respectively. There were no significant differences in the age, peak serum E(2) concentration, days of stimulation with rFSH, total number of M2 oocytes retrieved, number of embryos transferred, clinical pregnancy rates, and cancellation rates of stimulation and embryo transfer between the three groups except for total rFSH dosage. There is no need to use doses above 300 IU of rFSH to increase the pregnancy rate in microdose cycles. In addition, because the duration of stimulation does not differ between the groups, the usage of 300 IU rFSH in microdose cycles results in less total amount of rFSH consumed in a cycle compared with higher dosages, and this would obviously cost less money to the patients. Copyright 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Effect of an increased dosage of statins on spinal degenerative joint disease: a retrospective cohort study.

Science.gov (United States)

Cheng, Yuan-Yang; Kao, Chung-Lan; Lin, Shih-Yi; Chang, Shin-Tsu; Wei, Tz-Shiang; Chang, Shih-Ni; Lin, Ching-Heng

2018-02-08

It has been proven that statin can protect synovial joints from developing osteoarthritis through its anti-inflammatory effects. However, studies on the effect of statins on spinal degenerative joint diseases are few and limited to in vitro studies. Therefore, we investigated the relationship between the statin dosage and the development of spinal degenerative joint diseases. A retrospective cohort study. Patients registered in Taiwan National Health Insurance Research Database. Patients aged 40-65 years old from 2001 to 2010 were included. Those who received statin treatment before 2001, were diagnosed with spinal degenerative joint diseases or received any spinal surgery before 2004 or had any spinal trauma before 2011 were excluded. A total of 7238 statin users and 164 454 non-users were identified and followed up for the next 7 years to trace the development of spinal degenerative joint disease. The incident rate of spinal degenerative joint diseases and HRs among the groups treated with different statin dosages. A higher dosage of statins was associated with a significantly lower risk of developing spinal degenerative joint disease in patients with hypercholesterolaemia. Compared with the group receiving less than 5400 mg of a statin, the HR of the 11 900-28 000 mg group was 0.83 (95% CI 0.70 to 0.99), and that of the group receiving more than 28 000 mg was 0.81 (95% CI 0.68 to 0.97). Results of subgroup analysis showed a significantly lower risk in men, those aged 50-59 years and those with a monthly income less than US$600. Our study's findings clearly indicated that a higher dosage of statins can reduce the incidence of spinal degenerative joint disease in patients with hypercholesterolaemia, and it can be beneficial for people with a higher risk of spine degeneration. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise

Possible gene dosage effect of glutathione-S-transferases on atopic asthma: using real-time PCR for quantification of GSTM1 and GSTT1 gene copy numbers

DEFF Research Database (Denmark)

Brasch-Andersen, Charlotte; Christiansen, L; Tan, Q

2004-01-01

-S-transferase (GST) involved in the antioxidant defense were tested for association to asthma using 246 Danish atopic families in a family-based transmission disequilibrium test (TDT) design. A real-time PCR assay for relative quantification of gene copy number of GSTM1 and GSTT1 was developed. The assay made......Asthma is a complex genetic disorder characterized by chronic inflammation in the airways. As oxidative stress is a key component of inflammation, variations in genes involved in antioxidant defense could therefore be likely candidates for asthma. Three enzymes from the superfamily glutathione...

Cumulative dosages of antipsychotic drugs are associated with increased mortality rate in patients with Alzheimer's dementia

DEFF Research Database (Denmark)

Nielsen, R E; Lolk, A; Valentin, J B

2016-01-01

OBJECTIVE: We wished to investigate the effects of cumulative dosages of antipsychotic drug in Alzheimer's dementia, when controlling for known risk factors, including current antipsychotic exposure, on all-cause mortality. METHOD: We utilized a nationwide, population-based, retrospective cohort...... study design with mortality as outcome in individual patients diagnosed with Alzheimer's dementia. RESULTS: We included a total of 45 894 patients and followed them for 3 803 996 person-years in total, presenting 27 894 deaths in the study population. Cumulative antipsychotic exposure increased...... or equal to 730 DDDs: HR 1.06, 95% CI (0.95-1.18), P = 0.322, when controlling for proxy markers of severity, somatic and mental comorbid disorders. CONCLUSION: In this nationwide cohort study of 45 894 patients diagnosed with Alzheimer's dementia, we found that cumulative dosages of antipsychotic drugs...

Effects of increasing age, dosage, and duration of PTH treatment on BMD increase--a meta-analysis

DEFF Research Database (Denmark)

Schwarz, Peter; Jorgensen, Niklas Rye; Mosekilde, Leif

2012-01-01

were included. By metaregression analysis, we found that the increase in spine BMD (Z-score) after PTH treatment was blunted by increasing age (R (2) = 0.27; 2p = 0.01, slope -0.023 Z-scores per year, 11 studies). By increasing PTH dosage (μg/d), spine BMD increased significantly (2p = 0.......002) with a slope of +0.011 Z-scores/μg/d of teriparatide. Furthermore, the duration of treatment was positively correlated to spine BMD (P ......We studied the effects of increasing age, dosage, and duration of parathyroid hormone (PTH) treatment on changes in bone mineral density (BMD). Randomized placebo controlled trials on PTH treatment in men or women were retrieved from PubMed (1951 to present), Web of Science (1945 to present...

Plasma concentrations of caspofungin at two different dosage regimens in a patient with hepatic dysfunction

NARCIS (Netherlands)

van der Elst, K.C.; Bruggemann, R.J.M.; Rodgers, M.G.; Alffenaar, J.W.C.

2012-01-01

The currently recommended dosage regimen of caspofungin (50 mg/day) was developed for patients with invasive candidiasis. With invasive aspergillosis, successful outcomes occur in less than half the patients. We evaluate the pharmacokinetics in a patient with elevated liver enzyme levels after liver

Plasma concentrations of caspofungin at two different dosage regimens in a patient with hepatic dysfunction

NARCIS (Netherlands)

van der Elst, K. C. M.; Bruggemann, R. J. M.; Rodgers, M. G. G.; Alffenaar, J. W. C.

The currently recommended dosage regimen of caspofungin (50 mg/day) was developed for patients with invasive candidiasis. With invasive aspergillosis, successful outcomes occur in less than half the patients. We evaluate the pharmacokinetics in a patient with elevated liver enzyme levels after liver

A circadian gene expression atlas in mammals: implications for biology and medicine.

Science.gov (United States)

Zhang, Ray; Lahens, Nicholas F; Ballance, Heather I; Hughes, Michael E; Hogenesch, John B

2014-11-11

To characterize the role of the circadian clock in mouse physiology and behavior, we used RNA-seq and DNA arrays to quantify the transcriptomes of 12 mouse organs over time. We found 43% of all protein coding genes showed circadian rhythms in transcription somewhere in the body, largely in an organ-specific manner. In most organs, we noticed the expression of many oscillating genes peaked during transcriptional "rush hours" preceding dawn and dusk. Looking at the genomic landscape of rhythmic genes, we saw that they clustered together, were longer, and had more spliceforms than nonoscillating genes. Systems-level analysis revealed intricate rhythmic orchestration of gene pathways throughout the body. We also found oscillations in the expression of more than 1,000 known and novel noncoding RNAs (ncRNAs). Supporting their potential role in mediating clock function, ncRNAs conserved between mouse and human showed rhythmic expression in similar proportions as protein coding genes. Importantly, we also found that the majority of best-selling drugs and World Health Organization essential medicines directly target the products of rhythmic genes. Many of these drugs have short half-lives and may benefit from timed dosage. In sum, this study highlights critical, systemic, and surprising roles of the mammalian circadian clock and provides a blueprint for advancement in chronotherapy.

Assessment of tobramycin RIA for drug monitoring and dosage regimen. Comparison with other assay technics

International Nuclear Information System (INIS)

Takahashi, S.; Shinozaki, K.; Tsujino, D.; Ohhara, H.; Tanaka, Y.; Arai, S.; Someya, K.; Sasaki, Y.

1983-01-01

Because of wide range of inter-individual difference of pharmacokinetic parameter, importance of monitoring blood concentration of aminoglycoside antibiotics in each patient has been recognized. With the purpose to use for monitoring of serum tobramycin (TOB) levels and for adequate dosage regimen RIA of TOB was evaluated in comparison with other assay technics. Gamma Coat TOB RIA kits (Clinical Assay-Travenol Japan) were used for RIA of TOB. The TOB concentrations in the same samples were also measured by two kinds of enzyme immunoassay (EIA) (EMIT EIA and SLFIA EIA), High Performance Liquid Chromatography (HPLC) and bioassay (BA). RIA of TOB is a useful assay method with high sensitivity and reasonably good precision to be used for drug monitoring and adequate dosage regimen. Modification of the method for rapid assay of a small number of samples will increase the clinical usefulness in individualized drug monitoring

Predicting AEA dosage by Foam Index and adsorption on Fly Ash

OpenAIRE

Jacobsen, Stefan; Ollendorff, Margrethe; Geiker, Mette Rica; Tunstall, Lori; Scherer, George W.

2012-01-01

Abstract: The unpredictable air entrainment in fly ash concrete caused by carbon in fly ash was studied by measuring adsorption of Air Entraining Agents (AEA) on the fly ash and by Foam Index (FI) testing. The FI test measures the mass ratio of AEA/binder required to obtain stable foam when shaking a mixture of water, binder powder and AEA, while increasing AEA-dosage stepwise. A review of concrete air entrainment and new studies combining adsorption (TGA, NMR) of AEA on fly ash with various ...

Determination of Tannin and Saponin Dosage for Defaunation Improvement Feed Fermentability

OpenAIRE

Wahyuni, I.M. D; Muktiani, A; Christianto, M

2014-01-01

The research was conducted to evaluate the effect of addition of tannin, saponin or combination of tannin and saponin to the concentrate of the ration on the microbial population and fermentability of feed in vitro and to assess the best dosage of uses. The research was arranged according to completely randomized design with four treatments and 3 replications. The treatments were ration without tannin and saponin (T0), ration with 1.2% saponin (T1), ration with 0.5% tannin and 0.9% saponin (T...

Preparation, extraction and dosage of labelled cholesterol (D and C14)

International Nuclear Information System (INIS)

Bugnard, L.; Chevallier, F.; Coursaget, J.

1953-01-01

We returned in this note the techniques that we used for the preparation of labelled cholesterol. The chemical exchange of hydrogen enabling to contain deutero-cholesterol until 4 percent deuterium. The biologic synthesis, done on living rats or on their liver maintained in survival, permits, on the other hand, to get active cholesterol from acetate of containing sodium of the carbon 14. We indicated the techniques of extraction and dosage of the marked cholesterol. The radioactivity is measured with a Geiger-Muller counter. (M.B.) [fr

Saccharomyces cerevisiae ribosomal protein L37 is encoded by duplicate genes that are differentially expressed.

Science.gov (United States)

Tornow, J; Santangelo, G M

1994-06-01

A duplicate copy of the RPL37A gene (encoding ribosomal protein L37) was cloned and sequenced. The coding region of RPL37B is very similar to that of RPL37A, with only one conservative amino-acid difference. However, the intron and flanking sequences of the two genes are extremely dissimilar. Disruption experiments indicate that the two loci are not functionally equivalent: disruption of RPL37B was insignificant, but disruption of RPL37A severely impaired the growth rate of the cell. When both RPL37 loci are disrupted, the cell is unable to grow at all, indicating that rpL37 is an essential protein. The functional disparity between the two RPL37 loci could be explained by differential gene expression. The results of two experiments support this idea: gene fusion of RPL37A to a reporter gene resulted in six-fold higher mRNA levels than was generated by the same reporter gene fused to RPL37B, and a modest increase in gene dosage of RPL37B overcame the lack of a functional RPL37A gene.

The NSL Complex Regulates Housekeeping Genes in Drosophila

Science.gov (United States)

Raja, Sunil Jayaramaiah; Holz, Herbert; Luscombe, Nicholas M.; Manke, Thomas; Akhtar, Asifa

2012-01-01

MOF is the major histone H4 lysine 16-specific (H4K16) acetyltransferase in mammals and Drosophila. In flies, it is involved in the regulation of X-chromosomal and autosomal genes as part of the MSL and the NSL complexes, respectively. While the function of the MSL complex as a dosage compensation regulator is fairly well understood, the role of the NSL complex in gene regulation is still poorly characterized. Here we report a comprehensive ChIP–seq analysis of four NSL complex members (NSL1, NSL3, MBD-R2, and MCRS2) throughout the Drosophila melanogaster genome. Strikingly, the majority (85.5%) of NSL-bound genes are constitutively expressed across different cell types. We find that an increased abundance of the histone modifications H4K16ac, H3K4me2, H3K4me3, and H3K9ac in gene promoter regions is characteristic of NSL-targeted genes. Furthermore, we show that these genes have a well-defined nucleosome free region and broad transcription initiation patterns. Finally, by performing ChIP–seq analyses of RNA polymerase II (Pol II) in NSL1- and NSL3-depleted cells, we demonstrate that both NSL proteins are required for efficient recruitment of Pol II to NSL target gene promoters. The observed Pol II reduction coincides with compromised binding of TBP and TFIIB to target promoters, indicating that the NSL complex is required for optimal recruitment of the pre-initiation complex on target genes. Moreover, genes that undergo the most dramatic loss of Pol II upon NSL knockdowns tend to be enriched in DNA Replication–related Element (DRE). Taken together, our findings show that the MOF-containing NSL complex acts as a major regulator of housekeeping genes in flies by modulating initiation of Pol II transcription. PMID:22723752

An integrated system for dissolution studies and magnetic resonance imaging of controlled release, polymer-based dosage forms-a tool for quantitative assessment of hydrogel formation processes.

Science.gov (United States)

Kulinowski, Piotr; Dorozyński, Przemysław; Jachowicz, Renata; Weglarz, Władysław P

2008-11-04

Controlled release (CR) dosage forms are often based on polymeric matrices, e.g., sustained-release tablets and capsules. It is crucial to visualise and quantify processes of the hydrogel formation during the standard dissolution study. A method for imaging of CR, polymer-based dosage forms during dissolution study in vitro is presented. Imaging was performed in a non-invasive way by means of the magnetic resonance imaging (MRI). This study was designed to simulate in vivo conditions regarding temperature, volume, state and composition of dissolution media. Two formulations of hydrodynamically balanced systems (HBS) were chosen as model CR dosage forms. HBS release active substance in stomach while floating on the surface of the gastric content. Time evolutions of the diffusion region, hydrogel formation region and "dry core" region were obtained during a dissolution study of L-dopa as a model drug in two simulated gastric fluids (i.e. in fed and fasted state). This method seems to be a very promising tool for examining properties of new formulations of CR, polymer-based dosage forms or for comparison of generic and originator dosage forms before carrying out bioequivalence studies.

Long-term (5 years), high daily dosage of dietary agmatine--evidence of safety: a case report.

Science.gov (United States)

Gilad, Gad M; Gilad, Varda H

2014-11-01

There is presently a great interest in the therapeutic potential of agmatine, decarboxylated arginine, for various diseases. Recent clinical studies have already shown that oral agmatine sulfate given for up to 3 weeks provides a safe and, as compared with current therapeutics, more effective treatment for neuropathic pain. These studies have ushered in the use of dietary agmatine as a nutraceutical. However, in view of information paucity, assessment of long-term safety of oral agmatine treatment is now clearly required. The authors of this report undertook to assess their own health status during ongoing consumption of a high daily dosage of oral agmatine over a period of 4-5 years. A daily dose of 2.67 g agmatine sulfate was encapsulated in gelatin capsules; the regimen consists of six capsules daily, each containing 445 mg, three in the morning and three in the evening after meals. Clinical follow-up consists of periodic physical examinations and laboratory blood and urine analyses. All measurements thus far remain within normal values and good general health status is sustained throughout the study period, up to 5 years. This case study shows for the first time that the recommended high dosage of agmatine may be consumed for at least 5 years without evidence of any adverse effects. These initial findings are highly important as they provide significant evidence for the extended long-term safety of a high daily dosage of dietary agmatine--a cardinal advantage for its utility as a nutraceutical.

The Impact of Wine Style and Sugar Addition in liqueur d’expedition (dosage Solutions on Traditional Method Sparkling Wine Composition

Directory of Open Access Journals (Sweden)

Belinda Kemp

2017-01-01

Full Text Available The purpose of this study was to investigate the effect of wine style and cane sugar addition in the liqueur d’expedition (dosage solution on volatile aroma compounds (VOCs in traditional method sparkling wine. There were 24 bottles of each treatment produced. Treatments were sparkling wine zero dosage (ZD; NV sparkling wine + sugar (BS; unoaked still Chardonnay wine + sugar (UC; Pinot noir 2009 sparkling wine + sugar (PN; Niagara produced Brandy + sugar (B and Icewine (IW. The control treatment in the sensory analysis was an oaked still Chardonnay wine + sugar (OC because the zero-dosage wine was not suitable for a difference test that compared wines with sugar to one without. Standard wine chemical parameters were analysed before disgorging and after liqueur d’expedition was added and included; pH, titratable acidity (TA g/L, alcohol (v/v %, residual sugar (RS g/L, free and total SO2 and total phenolics (A.U.. Volatile aroma compounds (VOCs analysed by Headspace Solid- Phase Micro-Extraction Gas Chromatography-Mass Spectrometry (HS-SPME-GC-MS included two alcohols, and six ethyl esters. ZD wines had the highest foam height and highest dissolved oxygen level. Sugar affected VOC concentrations in all treatments at five weeks post-disgorging, but by 15 weeks after liqueur d’expedition addition, the wine with added sugar had similar VOC concentrations to the ZD wines. The type of wines used in the dosage solutions had more influence on VOC concentrations than sugar addition.

Spectrographic determination of chlorine and fluorine; Dosage du chlore et du fluor par spectrographie d'emission en atmosphere inerte

Energy Technology Data Exchange (ETDEWEB)

Contamin, G. [Commissariat a l' Energie Atomique, Grenoble (France). Centre d' Etudes Nucleaires

1965-04-01

Experimental conditions have been investigated in order to obtain the highest sensitivity in spectrographic determination of chlorine and fluorine using the Fassel method of excitation in an inert atmosphere. The influence of the nature of the atmosphere, of the discharge conditions and of the matrix material has been investigated. The following results have been established: 1. chlorine determination is definitely possible: a working curve has been drawn between 10 {mu}g and 100 {mu}g, the detection limit being around 5 {mu}g; 2. fluorine determination is not satisfactory: the detection limit is still of the order of 80 {mu}g. The best operating conditions have been defined for both elements. (author) [French] Nous avons recherche quelles etaient les conditions permettant d'obtenir la meilleure sensibilite dans le dosage spectrographique du chlore et du fluor par la methode d'excitation en atmosphere inerte (methode de Fassel). Nous avons etudie l'influence de l'atmosphere gazeuse, des conditions de la decharge et du materiau de pastillage. Les points suivants ont ete etablis: 1. le dosage du chlore est possible: une courbe de dosage a ete tracee entre 10 {mu}g et 100 {mu}g et la limite de detection est de l'ordre de 5 {mu}g; 2. le dosage du fluor n'est pas satisfaisant: la limite de detection obtenue etant encore de l'ordre de 80 {mu}g. Les conditions operatoires ont ete precisees pour ces deux elements. (auteur)

A Simple RP-HPLC Method for Quantitation of Itopride HCl in Tablet Dosage Form.

Science.gov (United States)

Thiruvengada, Rajan Vs; Mohamed, Saleem Ts; Ramkanth, S; Alagusundaram, M; Ganaprakash, K; Madhusudhana, Chetty C

2010-10-01

An isocratic reversed phase high-performance liquid chromatographic method with ultraviolet detection at 220 nm has been developed for the quantification of itopride hydrochloride in tablet dosage form. The quantification was carried out using C(8) column (250 mm × 4.6 mm), 5-μm particle size SS column. The mobile phase comprised of two solvents (Solvent A: buffer 1.4 mL ortho-phosphoric acid adjusted to pH 3.0 with triethyl amine and Solvent B: acetonitrile). The ratio of Solvent A: Solvent B was 75:25 v/v. The flow rate was 1.0 mL (-1)with UV detection at 220 nm. The method has been validated and proved to be robust. The calibration curve was linear in the concentration range of 80-120% with coefficient of correlation 0.9995. The percentage recovery for itopride HCl was 100.01%. The proposed method was validated for its selectivity, linearity, accuracy, and precision. The method was found to be suitable for the quality control of itopride HCl in tablet dosage formulation.

A fuzzy logic urea dosage controller design for two-cell selective catalytic reduction systems.

Science.gov (United States)

You, Kun; Wei, Lijiang; Jiang, Kai

2017-12-22

Diesel engines have dominated in the heavy-duty vehicular and marine power source. However, the induced air pollution is a big problem. As people's awareness of environmental protection increasing, the emission regulations of diesel-engine are becoming more stringent. In order to achieve the emission regulations, the after-treatment system is a necessary choice. Specifically, the selective catalytic reduction (SCR) system has been widely applied to reduce the NO X emissions of diesel engine. Different from single-cell SCR systems, the two-cell systems have various benefits from the modeling and control perspective. In this paper, the urea dosage controller design for two-cell SCR systems was investigated. Firstly, the two-cell SCR modeling was introduced. Based on the developed model, the design procedure for the fuzzy logic urea dosage controller was well addressed. Secondly, simulations and comparisons were employed via an experimental verification of the whole vehicle simulator. And the results showed that the designed controller simultaneously achieved high NO X reduction rate and low tail-pipe ammonia slip. Copyright © 2017 ISA. Published by Elsevier Ltd. All rights reserved.

ANTITUBERCULOSIS DRUG DOSAGE FORMS: RANGE, KEY BENEFITS AND PROSPECTS OF TECHNOLOGICAL IMPROVEMENT

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M. E. Kim

2016-01-01

Full Text Available Interest to research in the development of new formulations of antituberculosis drugs due to the high incidence of tuberculosis in the Republic of Kazakhstan and the Russian Federation nowadays, including with acquired drug resistance. The reason for the development of acquired drug resistance is to interrupt the treatment of patients is the high toxicity of antituberculosis drugs. The improving the efficiency of antituberculosis therapy remains one of the most pressing.The aim this study was to review the dosage forms of antituberculosis drugs currently used and the ways to improve them.Methods. The study was conducted on the basis of scientific analysis (eLibrary database, PubMed, Cyberleninca, patent (kzpatents, reference (Klifar, Drugs register and technical literature.Results. It was revealed that the antituberculosis drugs are available in the form of tablets, capsules, granules for oral use and injection solutions. The advantages and disadvantages of oral dosage forms of antituberculosis drugs: tablets, capsules, granules, syrups, suspensions are described. The importance of the development and implementation in practice of pediatric formulations of antituberculosis drugs is mentioned. The state of current research inhaled formulations for the treatment of tuberculosis is described. The prospects of directional inhalation exposure by immobilization of antituberculosis drugs in liposomes, niosomes, nanocapsules, micelles, micro- and nanoparticles are mentioned. The prospect of the rectal formulations use is described. The increase in interest in the molecular encapsulation of medicinal substances with cyclodextrins in connection with the possibility of increasing the bioavailability of active ingredients, reduce the harmful effects on the gastrointestinal tract, extension, elimination of interaction of incompatible components in combination preparations, the protection of unstable substances is

Micropellets coated with Kollicoat® Smartseal 30D for taste masking in liquid oral dosage forms.

Science.gov (United States)

Dashevskiy, Andriy; Mohylyuk, Valentyn; Ahmed, Abid Riaz; Kolter, Karl; Guth, Felicitas; Bodmeier, Roland

2017-09-01

The objective of this study was to develop delivery systems for taste masking based on multiparticulates coated with Kollicoat ® Smartseal 30D formulated as liquid oral suspensions. Coating of particles containing bitter drugs with Kollicoat ® Smartseal reduced drug leaching into aqueous medium, especially when increasing pH, therefore can be used for the formulation of liquid dosage forms. Application of an intermediate layer of ion exchange resins between drug layer and coating can further decrease drug leaching into aqueous vehicle that is beneficial in terms of taste masking. Using optimized compositions of liquid vehicles such as addition of sugar alcohols and ion exchange resin, reconstitutable or ready-to-use liquid dosage forms with micropellets can be developed with bitter taste protection after redispersion lasting longer than 3 weeks, which exceeds the usual period of application.

Influence of the fuel and dosage on the performance of double-compartment microbial fuel cells.

Science.gov (United States)

Asensio, Y; Fernandez-Marchante, C M; Lobato, J; Cañizares, P; Rodrigo, M A

2016-08-01

This manuscript focuses on the evaluation of the use of different types and dosages of fuels in the performance of double-compartment microbial fuel cell equipped with carbon felt electrodes and cationic membrane. Five types of fuels (ethanol, glycerol, acetate, propionate and fructose) have been tested for the same organic load (5,000 mg L(-1) measured as COD) and for one of them (acetate), the range of dosages between 500 and 20,000 mg L(-1) of COD was also studied. Results demonstrate that production of electricity depends strongly on the fuel used. Carboxylic acids are much more efficient than alcohols or fructose for the same organic load and within the range 500-5,000 mg L(-1) of acetate the production of electricity increases linearly with the amount of acetate fed but over these concentrations a change in the population composition may explain a worse performance. Copyright © 2016 Elsevier Ltd. All rights reserved.

Effect of Injection Minimal Dosages of Depot Medroxyprogesterone acetate (DMPA to Body Weight and Blood Chemistry Male Rat Strain Sprague-Dawley

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Nukman Moeloek

2009-11-01

Full Text Available Many family planning program focus more on men. Until now, vasectomy has been the commonly used method for male contraception. However, this method creates inconvenience such as irreversibility and psychological problems. One of the alternatives contraception is the combination of depot medroxyprogesterone acetate (DMPA and androgen. The minimum dosage of DMPA could suppress testosterone level that leads to reduced spermatogenesis and sperm viability. Nevertheless, until now it is not known whether minimum dosages of DMPA have an effect to body weight and blood chemistry. Therefore, this research aimed at determinate the effect of minimal dosages of DMPA to body mass and blood chemistry using male rats (Rattus norvegicus L. strain Sprague-Dawley as model. This research using completely randomized design, unequal size sample, castration treatments and several doses DMPA (1.25, 0.625, and 0.313 milligram. Injecting of DMPA conducted intramuscularly on week 0 and week 12. Normality/homogeneity Data normality were analyzed before ANOVA test. Then, abnormal data were tested using Kruskal-Wallis test. The result shows that injection of DMPA in various doses do not have an effect on body weight and blood chemistry such as erytrocytes, haemoglobin, hematocrite, HDL, LDL, total cholesterol, SGOT, SGPT and triglyseride (p>0,05. Furthermore, it is concluded that that no effect of minimal dosages of DMPA to body mass and blood chemistry of rat.

Automatic dosage of hydrogen peroxide in solar photo-Fenton plants: Development of a control strategy for efficiency enhancement

Energy Technology Data Exchange (ETDEWEB)

Ortega-Gomez, E. [Department of Chemical Engineering, University of Almeria, 04120 Almeria (Spain); CIESOL, Joint Centre of the University of Almeria-CIEMAT, 04120 Almeria (Spain); Moreno Ubeda, J.C. [Department of Language and Computation, University of Almeria, 04120 Almeria (Spain); Alvarez Hervas, J.D. [Department of Language and Computation, University of Almeria, 04120 Almeria (Spain); Department of Language and Computation, University of Sevilla, 41092 Sevilla (Spain); Casas Lopez, J.L.; Santos-Juanes Jorda, L. [Department of Chemical Engineering, University of Almeria, 04120 Almeria (Spain); CIESOL, Joint Centre of the University of Almeria-CIEMAT, 04120 Almeria (Spain); Sanchez Perez, J.A., E-mail: jsanchez@ual.es [Department of Chemical Engineering, University of Almeria, 04120 Almeria (Spain); CIESOL, Joint Centre of the University of Almeria-CIEMAT, 04120 Almeria (Spain)

2012-10-30

Highlights: Black-Right-Pointing-Pointer Dissolved oxygen monitoring is used for automatic dosage of H{sub 2}O{sub 2} in photo-Fenton. Black-Right-Pointing-Pointer PI with anti-windup minimises H{sub 2}O{sub 2} consumption. Black-Right-Pointing-Pointer The H{sub 2}O{sub 2} consumption was reduced up to 50% with respect to manual addition strategies. Black-Right-Pointing-Pointer Appropriate H{sub 2}O{sub 2} dosage is achieved by PI with anti-windup under disturbances. - Abstract: The solar photo-Fenton process is widely used for the elimination of pollutants in aqueous effluent and, as such, is amply cited in the literature. In this process, hydrogen peroxide represents the highest operational cost. Up until now, manual dosing of H{sub 2}O{sub 2} has led to low process performance. Consequently, there is a need to automate the hydrogen peroxide dosage for use in industrial applications. As it has been demonstrated that a relationship exists between dissolved oxygen (DO) concentration and hydrogen peroxide consumption, DO can be used as a variable in optimising the hydrogen peroxide dosage. For this purpose, a model was experimentally obtained linking the dynamic behaviour of DO to hydrogen peroxide consumption. Following this, a control system was developed based on this model. This control system - a proportional and integral controller (PI) with an anti-windup mechanism - has been tested experimentally. The assays were carried out in a pilot plant under sunlight conditions and with paracetamol used as the model pollutant. In comparison with non-assisted addition methods (a sole initial or continuous addition), a decrease of 50% in hydrogen peroxide consumption was achieved when the automatic controller was used, driving an economic saving and an improvement in process efficiency.

Polymorphisms of the GR and HSD11B1 genes influence body mass index and weight gain during hormone replacement treatment in patients with Addison's disease.

Science.gov (United States)

Molnár, Ágnes; Kövesdi, Annamária; Szücs, Nikolette; Tóth, Miklós; Igaz, Péter; Rácz, Károly; Patócs, Attila

2016-08-01

Glucocorticoid substitution is essential in patients with chronic primary adrenocortical insufficiency (Addison's disease) and both over-treatment and inadequate dosage have deleterious effects. Individual sensitivity to glucocorticoids is partly genetically determined. To test the hypothesis whether the well-characterized SNPs of the GR and HSD11B1 genes may modulate the individual sensitivity to exogenous glucocorticoids and may influence clinical and/or laboratory parameters and the glucocorticoid substitution dosage in patients with Addison's disease. 68 patients with primary adrenocortical insufficiency were involved. Clinical and laboratory data, as well as the dosage of the hormone replacement therapy were collected. Peripheral blood DNA was isolated, and the GR and HSD11B1 SNPs were examined using allele-specific PCR or Taqman assay on Real Time PCR. The allele frequency of the GR N363S polymorphism was higher in patients compared to the control group and the disease appeared significantly earlier in patients harbouring the GR A3669G compared to noncarriers. These patients had higher ACTH level measured at the time of diagnosis. Homozygous BclI carriers had higher body mass index (BMI) and lower total hydrocortisone equivalent supplementation dose needed than heterozygous or noncarriers. The BMI and weight gain during hormone replacement therapy were also higher in carriers of the HSD11B1 rs4844880 treated with glucocorticoids other than dexamethasone. The BclI polymorphism of the GR gene and the rs4844880 of the HSD11B1 gene may contribute to weight gain and may affect the individual need of glucocorticoid substitution dose in these patients. © 2016 John Wiley & Sons Ltd.

Noninvasive prenatal diagnosis for single gene disorders.

Science.gov (United States)

Allen, Stephanie; Young, Elizabeth; Bowns, Benjamin

2017-04-01

Noninvasive prenatal diagnosis for single gene disorders is coming to fruition in its clinical utility. The presence of cell-free DNA in maternal plasma has been recognized for many years, and a number of applications have developed from this. Noninvasive prenatal diagnosis for single gene disorders has lagged behind due to complexities of technology development, lack of investment and the need for validation samples for rare disorders. Publications are emerging demonstrating a variety of technical approaches and feasibility of clinical application. Techniques for analysis of cell-free DNA including digital PCR, next-generation sequencing and relative haplotype dosage have been used most often for assay development. Analysis of circulating fetal cells in the maternal blood is still being investigated as a viable alternative and more recently transcervical trophoblast cells. Studies exploring ethical and social issues are generally positive but raise concerns around the routinization of prenatal testing. Further work is necessary to make testing available to all patients with a pregnancy at risk of a single gene disorder, and it remains to be seen if the development of more powerful technologies such as isolation and analysis of single cells will shift the emphasis of noninvasive prenatal diagnosis. As testing becomes possible for a wider range of conditions, more ethical questions will become relevant.

Higher dosage nicotine patches increase one-year smoking cessation rates : results from the European CEASE trial

NARCIS (Netherlands)

Tonnesen, P; Paoletti, P; Gustavsson, G; Russell, MA; Saracci, R; Gulsvik, A; Rijcken, B

The Collaborative European Anti-Smoking Evaluation (CEASE) was a European multicentre, randomized, double-blind placebo controlled smoking cessation study, The objectives were to determine whether higher dosage and longer duration of nicotine patch therapy would increase the success rate. Thirty-six

Improved sentinel node visualization in breast cancer by optimizing the colloid particle concentration and tracer dosage

NARCIS (Netherlands)

Valdés Olmos, R. A.; Tanis, P. J.; Hoefnagel, C. A.; Nieweg, O. E.; Muller, S. H.; Rutgers, E. J.; Kooi, M. L.; Kroon, B. B.

2001-01-01

Faint lymph uptake may hamper sentinel node (SN) identification by scintigraphy and subsequent gamma probe localization. The aim of the present study was to evaluate an adjustment in the colloid particle concentration and tracer dosage to optimize mammary lymphoscintigraphy. Scintigraphy was

Cohort-specific imputation of gene expression improves prediction of warfarin dose for African Americans.

Science.gov (United States)

Gottlieb, Assaf; Daneshjou, Roxana; DeGorter, Marianne; Bourgeois, Stephane; Svensson, Peter J; Wadelius, Mia; Deloukas, Panos; Montgomery, Stephen B; Altman, Russ B

2017-11-24

Genome-wide association studies are useful for discovering genotype-phenotype associations but are limited because they require large cohorts to identify a signal, which can be population-specific. Mapping genetic variation to genes improves power and allows the effects of both protein-coding variation as well as variation in expression to be combined into "gene level" effects. Previous work has shown that warfarin dose can be predicted using information from genetic variation that affects protein-coding regions. Here, we introduce a method that improves dose prediction by integrating tissue-specific gene expression. In particular, we use drug pathways and expression quantitative trait loci knowledge to impute gene expression-on the assumption that differential expression of key pathway genes may impact dose requirement. We focus on 116 genes from the pharmacokinetic and pharmacodynamic pathways of warfarin within training and validation sets comprising both European and African-descent individuals. We build gene-tissue signatures associated with warfarin dose in a cohort-specific manner and identify a signature of 11 gene-tissue pairs that significantly augments the International Warfarin Pharmacogenetics Consortium dosage-prediction algorithm in both populations. Our results demonstrate that imputed expression can improve dose prediction and bridge population-specific compositions. MATLAB code is available at https://github.com/assafgo/warfarin-cohort.

Paracetamol in therapeutic dosages and acute liver injury: causality assessment in a prospective case series

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Castellote José

2011-07-01

Full Text Available Abstract Background Acute liver injury (ALI induced by paracetamol overdose is a well known cause of emergency hospital admission and death. However, there is debate regarding the risk of ALI after therapeutic dosages of the drug. The aim is to describe the characteristics of patients admitted to hospital with jaundice who had previous exposure to therapeutic doses of paracetamol. An assessment of the causality role of paracetamol was performed in each case. Methods Based on the evaluation of prospectively gathered cases of ALI with detailed clinical information, thirty-two cases of ALI in non-alcoholic patients exposed to therapeutic doses of paracetamol were identified. Two authors assessed all drug exposures by using the CIOMS/RUCAM scale. Each case was classified into one of five categories based on the causality score for paracetamol. Results In four cases the role of paracetamol was judged to be unrelated, in two unlikely, and these were excluded from evaluation. In seven of the remaining 26 cases, the RUCAM score associated with paracetamol was higher than that associated with other concomitant medications. The estimated incidence of ALI related to the use of paracetamol in therapeutic dosages was 0.4 per million inhabitants older than 15 years of age and per year (99%CI, 0.2-0.8 and of 10 per million paracetamol users-year (95% CI 4.3-19.4. Conclusions Our results indicate that paracetamol in therapeutic dosages may be considered in the causality assessment in non-alcoholic patients with liver injury, even if the estimated incidence of ALI related to paracetamol appears to be low.

Chronic exposure to low doses of pharmaceuticals disturbs the hepatic expression of circadian genes in lean and obese mice

Energy Technology Data Exchange (ETDEWEB)

Anthérieu, Sébastien; Le Guillou, Dounia; Coulouarn, Cédric; Begriche, Karima [INSERM, U991, Université de Rennes 1, 35000 Rennes (France); Trak-Smayra, Viviane [Pathology Department, Saint-Joseph University, Beirut (Lebanon); Martinais, Sophie [INSERM, U991, Université de Rennes 1, 35000 Rennes (France); Porceddu, Mathieu [Mitologics SAS, Hôpital Robert Debré, 48 Boulevard Sérurier, 75019 Paris (France); Robin, Marie-Anne [INSERM, U991, Université de Rennes 1, 35000 Rennes (France); Fromenty, Bernard, E-mail: bernard.fromenty@inserm.fr [INSERM, U991, Université de Rennes 1, 35000 Rennes (France)

2014-04-01

Drinking water can be contaminated with pharmaceuticals. However, it is uncertain whether this contamination can be harmful for the liver, especially during obesity. Hence, the goal of our study was to determine whether chronic exposure to low doses of pharmaceuticals could have deleterious effects on livers of lean and obese mice. To this end, lean and ob/ob male mice were treated for 4 months with a mixture of 11 drugs provided in drinking water at concentrations ranging from 10 to 10{sup 6} ng/l. At the end of the treatment, some liver and plasma abnormalities were observed in ob/ob mice treated with the cocktail containing 10{sup 6} ng/l of each drug. For this dosage, a gene expression analysis by microarray showed altered expression of circadian genes (e.g. Bmal1, Dbp, Cry1) in lean and obese mice. RT-qPCR analyses carried out in all groups of animals confirmed that expression of 8 different circadian genes was modified in a dose-dependent manner. For some genes, a significant modification was observed for dosages as low as 10{sup 2}–10{sup 3} ng/l. Drug mixture and obesity presented an additive effect on circadian gene expression. These data were validated in an independent study performed in female mice. Thus, our study showed that chronic exposure to trace pharmaceuticals disturbed hepatic expression of circadian genes, particularly in obese mice. Because some of the 11 drugs can be found in drinking water at such concentrations (e.g. acetaminophen, carbamazepine, ibuprofen) our data could be relevant in environmental toxicology, especially for obese individuals exposed to these contaminants. - Highlights: • The contamination of drinking water with drugs may have harmful effects on health. • Some drugs can be more hepatotoxic in the context of obesity and fatty liver. • Effects of chronic exposure of trace drugs were studied in lean and obese mouse liver. Drugs and obesity present additive effects on circadian gene expression and toxicity. • Trace

The knowledge, attitudes and beliefs of patients and their healthcare professionals around oral dosage form modification: A systematic review of the qualitative literature.

Science.gov (United States)

Mc Gillicuddy, Aoife; Kelly, Maria; Crean, Abina M; Sahm, Laura J

The objective of this systematic review was to synthesize the available qualitative evidence on the knowledge, attitudes and beliefs of adult patients, healthcare professionals and carers about oral dosage form modification. A systematic review and synthesis of qualitative studies was undertaken, utilising the thematic synthesis approach. The following databases were searched from inception to September 2015: PubMed, Medline (EBSCO), EMBASE, CINAHL, PsycINFO, Web of Science, ProQuest Databases, Scopus, Turning Research Into Practice (TRIP), Cochrane Central Register of Controlled Trials (CENTRAL) and the Cochrane Database of Systematic Reviews (CDSR). Citation tracking and searching the references lists of included studies was also undertaken. Grey literature was searched using the OpenGrey database, internet searching and personal knowledge. An updated search was undertaken in June 2016. Studies meeting the following criteria were eligible for inclusion; (i) used qualitative data collection and analysis methods; (ii) full-text was available in English; (iii) included adult patients who require oral dosage forms to be modified to meet their needs or; (iv) carers or healthcare professionals of patients who require oral dosage forms to be modified. Two reviewers independently appraised the quality of the included studies using the Critical Appraisal Skills Programme Checklist. A thematic synthesis was conducted and analytical themes were generated. Of 5455 records screened, seven studies were eligible for inclusion; three involved healthcare professionals and the remaining four studies involved patients. Four analytical themes emerged from the thematic synthesis: (i) patient-centred individuality and variability; (ii) communication; (iii) knowledge and uncertainty and; (iv) complexity. The variability of individual patient's requirements, poor communication practices and lack of knowledge about oral dosage form modification, when combined with the complex and multi

New exercise-integrated technology can monitor the dosage and quality of exercise performed against an elastic resistance band by adolescents with patellofemoral pain

DEFF Research Database (Denmark)

Rathleff, Michael S; Bandholm, Thomas; McGirr, Kate A

2016-01-01

QUESTION: Is the exercise-integrated Bandcizer™ system feasible for recording exercise dosage (time under tension (TUT) and repetitions) and pain scores among adolescents with patellofemoral pain? Do adolescents practise the exercises as prescribed (TUT and repetitions)? Do adolescents accurately...... report the exercises they do in an exercise diary? DESIGN: Observational feasibility study. PARTICIPANTS: Twenty adolescents between 15 and 19 years of age with patellofemoral pain. INTERVENTION: Participants were prescribed three exercise sessions per week (one with and two without supervision) for 6......% of the instructed exercise dosage based on TUT. The exercise dosage reported in the exercise diaries was 2.3 times higher than the TUT data from the electronic system. Pain intensity was successfully collected in 100% of the exercise sets. CONCLUSION: The system was feasible for adolescents with patellofemoral pain...

PFOS prenatal exposure induce mitochondrial injury and gene expression change in hearts of weaned SD rats

International Nuclear Information System (INIS)

Xia, Wei; Wan, Yanjian; Li, Yuan-yuan; Zeng, Huaicai; Lv, Ziquan; Li, Gengqi; Wei, Zhengzheng; Xu, Shun-qing

2011-01-01

Xenobiotics exposure in early life may have adverse effects on animals' development through mitochondrial injury or dysfunction. The current study demonstrated the possibility of cardiac mitochondrial injury in prenatal PFOS-exposed weaned rat heart. Pregnant Sprague-Dawley (SD) rats were exposed to perfluorooctane sulfonate (PFOS) at doses of 0.1, 0.6 and 2.0 mg/kg/d and 0.05% Tween 80 as control by gavage from gestation days 2-21. The dams were allowed to give nature delivery and then heart tissues from weaned (postnatal day 21) offspring rats were analyzed for mitochondrial injury through ultrastructure observation by electron microscope, global gene expression profile by microarray, as well as related mRNA and proteins expression levels by quantitative PCR and western blot. Ultrastructural analysis revealed significant vacuolization and inner membrane injury occurred at the mitochondria of heart tissues from 2.0 mg/kg/d dosage group. Meanwhile, the global gene expression profile showed significant difference in level of some mRNA expression associated with mitochondrial function at 2.0 mg/kg/d dosage group, compared to the control. Furthermore, dose-response trends for the expression of selected genes were analyzed by quantitative PCR and western blot analysis. The selected genes were mainly focused on those encoding for proteins involved in energy production, control of ion levels, and maintenance of heart function. The down-regulation of mitochondrial ATP synthetase (ATP5E, ATP5I and ATP5O) implicated a decrease in energy supply. This was accompanied by down-regulation of gene transcripts involved in energy consumption such as ion transporting ATPase (ATP1A3 and ATP2B2) and inner membrane protein synthesis (SLC25A3, SLC25A4, SLC25A10, SLC25A29). The up-regulation of gene transcripts encoding for uncoupling proteins (UCP1 and UCP3), epidermal growth factor receptor (EGFR) and connective tissue growth factor (CTGF), was probably a protective process to maintain

A new resource for characterizing X-linked genes in Drosophila melanogaster: systematic coverage and subdivision of the X chromosome with nested, Y-linked duplications.

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Cook, R Kimberley; Deal, Megan E; Deal, Jennifer A; Garton, Russell D; Brown, C Adam; Ward, Megan E; Andrade, Rachel S; Spana, Eric P; Kaufman, Thomas C; Cook, Kevin R

2010-12-01

Interchromosomal duplications are especially important for the study of X-linked genes. Males inheriting a mutation in a vital X-linked gene cannot survive unless there is a wild-type copy of the gene duplicated elsewhere in the genome. Rescuing the lethality of an X-linked mutation with a duplication allows the mutation to be used experimentally in complementation tests and other genetic crosses and it maps the mutated gene to a defined chromosomal region. Duplications can also be used to screen for dosage-dependent enhancers and suppressors of mutant phenotypes as a way to identify genes involved in the same biological process. We describe an ongoing project in Drosophila melanogaster to generate comprehensive coverage and extensive breakpoint subdivision of the X chromosome with megabase-scale X segments borne on Y chromosomes. The in vivo method involves the creation of X inversions on attached-XY chromosomes by FLP-FRT site-specific recombination technology followed by irradiation to induce large internal X deletions. The resulting chromosomes consist of the X tip, a medial X segment placed near the tip by an inversion, and a full Y. A nested set of medial duplicated segments is derived from each inversion precursor. We have constructed a set of inversions on attached-XY chromosomes that enable us to isolate nested duplicated segments from all X regions. To date, our screens have provided a minimum of 78% X coverage with duplication breakpoints spaced a median of nine genes apart. These duplication chromosomes will be valuable resources for rescuing and mapping X-linked mutations and identifying dosage-dependent modifiers of mutant phenotypes.

Study of Bokashi’s Type and Dosages to Growth and Harvest Yield Honey Dews (Cucumis Melo L. In Low Land

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Ana Amiroh

2016-12-01

Full Text Available Recently, most cultivation and planting of Melon (Cucumis melo L. by farmers using inorganic fertilizers with an excessive dosage, and this causes the lowland productivity decrease with consequent. The soil organic matter decreased as low as time increasing. Application and using of mature organic matter are an alternative to solve these problems in order the lowland become more conducive and productive for growth of melon. But increasing pests and diseases attaching to the plants may caused by adding immature organic matters into soil. Sources to make bokashi like as paddy straw and water hyacinth is immense but it’s not yet used. This research was aimed to study, know and usage of paddy straw and water hyacinth bokashi’s on melon growing at lowland. Experiment was conducted at Lowland Experiment Station of Agricultural Faculty, Brawijaya, in Jatikerto Village, Kromengan Distric, Malang, from April-June 2015. Experiment was applied in a Randomized Block Design (RBD with double factors Types and Dosages of Bokashis. There is seven combinations of treatment with three replications, each treatment consisted four individual plants. Result showed there is significant difference between types and dosages of bokashi on plant length at 28, 35, 42 dan 49 days after planting (d,a,p respectively. The significant difference between treatment also shown by leaf area at 28 - 49 (d.a.p.. Application of paddy straw bokashi was better than hyacinth bokashi on melon growth. The best yield shows that by using paddy straw bokashi with 5 ton/ha of dosage gives melon with 2,56 kg /plant fresh weight.

Hybrid incompatibilities are affected by dominance and dosage in the haplodiploid wasp Nasonia

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Beukeboom, Leo W.; Koevoets, Tosca; Morales, Hernán E.; Ferber, Steven; van de Zande, Louis

2015-01-01

Study of genome incompatibilities in species hybrids is important for understanding the genetic basis of reproductive isolation and speciation. According to Haldane's rule hybridization affects the heterogametic sex more than the homogametic sex. Several theories have been proposed that attribute asymmetry in hybridization effects to either phenotype (sex) or genotype (heterogamety). Here we investigate the genetic basis of hybrid genome incompatibility in the haplodiploid wasp Nasonia using the powerful features of haploid males and sex reversal. We separately investigate the effects of heterozygosity (ploidy level) and sex by generating sex reversed diploid hybrid males and comparing them to genotypically similar haploid hybrid males and diploid hybrid females. Hybrid effects of sterility were more pronounced than of inviability, and were particularly strong in haploid males, but weak to absent in diploid males and females, indicating a strong ploidy level but no sex specific effect. Molecular markers identified a number of genomic regions associated with hybrid inviability in haploid males that disappeared under diploidy in both hybrid males and females. Hybrid inviability was rescued by dominance effects at some genomic regions, but aggravated or alleviated by dosage effects at other regions, consistent with cytonuclear incompatibilities. Dosage effects underlying Bateson–Dobzhansky–Muller (BDM) incompatibilities need more consideration in explaining Haldane's rule in diploid systems. PMID:25926847

COMPARISON OF THE NEW IRON DOSAGE METHODS FOR DRINKING WATER PRODUCTION

DEFF Research Database (Denmark)

Kowalski, Krysztof; Søgaard, Erik Gydesen

Arsenic is considered as one of the most concerned pollutants in the world due to its adverse health effects. Therefore, its content in drinking water has been recommended to be limited to 10 μg/L (WHO 2006). On of the conventional methods for arsenic removal is based on the addition of ferrous......, it can be controlled, which brings main advantage in large scale water processing. However, both techniques have limitations, which results in different area of implementation. The aim of this work is to compare and evaluate new iron dosage methods by comparing the water treatment plants where ZVI...

Study of hydrogels based on polyacrilamide as new controlled release dosage forms produced by frontal polymerization

OpenAIRE

Sechi, Rossana; Gavini, Elisabetta; Mariani, Alberto; Bidali, Simone; Bonferoni, Maria Cristina; Sanna, Vanna Annunziata; Rassu, Giovanna; Pirisino, Gerolamo Antonio; Giunchedi, Paolo

2006-01-01

The work purpose was the evaluation of the potential application of the Frontal Polymerization (FP) technique as a new method for the preparation of controlled release dosage forms based on polyacrilamide, in which the drug loading and the polymer preparation occur at the same time.

Population Level Purifying Selection and Gene Expression Shape Subgenome Evolution in Maize.

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Pophaly, Saurabh D; Tellier, Aurélien

2015-12-01

The maize ancestor experienced a recent whole-genome duplication (WGD) followed by gene erosion which generated two subgenomes, the dominant subgenome (maize1) experiencing fewer deletions than maize2. We take advantage of available extensive polymorphism and gene expression data in maize to study purifying selection and gene expression divergence between WGD retained paralog pairs. We first report a strong correlation in nucleotide diversity between duplicate pairs, except for upstream regions. We then show that maize1 genes are under stronger purifying selection than maize2. WGD retained genes have higher gene dosage and biased Gene Ontologies consistent with previous studies. The relative gene expression of paralogs across tissues demonstrates that 98% of duplicate pairs have either subfunctionalized in a tissuewise manner or have diverged consistently in their expression thereby preventing functional complementation. Tissuewise subfunctionalization seems to be a hallmark of transcription factors, whereas consistent repression occurs for macromolecular complexes. We show that dominant gene expression is a strong determinant of the strength of purifying selection, explaining the inferred stronger negative selection on maize1 genes. We propose a novel expression-based classification of duplicates which is more robust to explain observed polymorphism patterns than the subgenome location. Finally, upstream regions of repressed genes exhibit an enrichment in transposable elements which indicates a possible mechanism for expression divergence. © The Author 2015. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Spectrophotometric simultaneous determination of Rabeprazole Sodium and Itopride Hydrochloride in capsule dosage form

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Sabnis, Shweta S.; Dhavale, Nilesh D.; Jadhav, Vijay. Y.; Gandhi, Santosh V.

2008-03-01

A new simple, economical, rapid, precise and accurate method for simultaneous determination of rabeprazole sodium and itopride hydrochloride in capsule dosage form has been developed. The method is based on ratio spectra derivative spectrophotometry. The amplitudes in the first derivative of the corresponding ratio spectra at 231 nm (minima) and 260 nm were selected to determine rabeprazole sodium and itopride hydrochloride, respectively. The method was validated with respect to linearity, precision and accuracy.

Impact of Room Location on UV-C Irradiance and UV-C Dosage and Antimicrobial Effect Delivered by a Mobile UV-C Light Device.

Science.gov (United States)

Boyce, John M; Farrel, Patricia A; Towle, Dana; Fekieta, Renee; Aniskiewicz, Michael

2016-06-01

OBJECTIVE To evaluate ultraviolet C (UV-C) irradiance, UV-C dosage, and antimicrobial effect achieved by a mobile continuous UV-C device. DESIGN Prospective observational study. METHODS We used 6 UV light sensors to determine UV-C irradiance (W/cm2) and UV-C dosage (µWsec/cm2) at various distances from and orientations relative to the UV-C device during 5-minute and 15-minute cycles in an ICU room and a surgical ward room. In both rooms, stainless-steel disks inoculated with methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus (VRE), and Clostridium difficile spores were placed next to sensors, and UV-C dosages and log10 reductions of target organisms achieved during 5-minute and 15-minute cycles were determined. Mean irradiance and dosage readings were compared using ANOVA. RESULTS Mean UV-C irradiance was nearly 1.0E-03 W/cm2 in direct sight at a distance of 1.3 m (4 ft) from the device but was 1.12E-05 W/cm2 on a horizontal surface in a shaded area 3.3 m (10 ft) from the device (P4 to 1-3 for MRSA, >4 to 1-2 for VRE and >4 to 0 log10 for C. difficile spores, depending on the distance from, and orientation relative to, the device with 5-minute and 15-minute cycles. CONCLUSION UV-C irradiance, dosage, and antimicrobial effect received from a mobile UV-C device varied substantially based on location in a room relative to the UV-C device. Infect Control Hosp Epidemiol 2016;37:667-672.

Avascular necrosis of the femoral head post heart-transplantation and steroid dosage.

Science.gov (United States)

Foley-Nolan, D; Daly, C; Barry, C; Woods, A; Neligan, M; Coughlan, R J

1992-12-01

Avascular necrosis (avn) post heart-transplantation has been considered to be due to the high doses of steroids used to immunosuppress these patients in attempting to prevent transplant rejection. This study shows that avascular necrosis occurs even when low dose steroids regimes are used and demonstrates no significant correlation between steroid dosage and the development of avn. Patients with symptomatic avn benefit from early diagnosis and management of their condition in that the need for total joint arthroplasty can be prevented in many cases.

Efficacy of a DNA Vaccine Carrying Eimeria maxima Gam56 Antigen Gene against Coccidiosis in Chickens

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Xu, Jinjun; Zhang, Yan

2013-01-01

To control coccidiosis without using prophylactic medications, a DNA vaccine targeting the gametophyte antigen Gam56 from Eimeria maxima in chickens was constructed, and the immunogenicity and protective effects were evaluated. The ORF of Gam56 gene was cloned into an eukaryotic expression vector pcDNA3.1(zeo)+. Expression of Gam56 protein in COS-7 cells transfected with recombinant plasmid pcDNA-Gam56 was confirmed by indirect immunofluorescence assay. The DNA vaccine was injected intramuscularly to yellow feathered broilers of 1-week old at 3 dosages (25, 50, and 100 µg/chick). Injection was repeated once 1 week later. One week after the second injection, birds were challenged orally with 5×104 sporulated oocysts of E. maxima, then weighed and killed at day 8 post challenge. Blood samples were collected and examined for specific peripheral blood lymphocyte proliferation activity and serum antibody levels. Compared with control groups, the administration of pcDNA-Gam56 vaccine markedly increased the lymphocyte proliferation activity (P<0.05) at day 7 and 14 after the first immunization. The level of lymphocyte proliferation started to decrease on day 21 after the first immunization. A similar trend was seen in specific antibody levels. Among the 3 pcDNA-Gam56 immunized groups, the median dosage group displayed the highest lymphocyte proliferation and antibody levels (P<0.05). The median dosage group had the greatest relative body weight gain (89.7%), and the greatest oocyst shedding reduction (53.7%). These results indicate that median dosage of DNA vaccine had good immunogenicity and immune protection effects, and may be used in field applications for coccidiosis control. PMID:23710081

The Importance of Superplastizer Dosage in the Mix Design of Lightweight Aggregate Concrete Reinforced With Plypropylene Fiber

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Shafigh Payam

2016-01-01

Full Text Available This paper reports the results of a study conducted to investigate the effect of superplasticizer (SP dosage on the slump, density, compressive strength and splitting tensile strength under different curing conditions of a lightweight aggregate concrete reinforced with polypropylene (PP fiber. The lightweight aggregate used in this study was oil palm shell, which is an agricultural solid waste, originating from the palm oil industry. The results indicated that an increase in superplasticizer increased the workability, however, all the mechanical properties declined significantly. The reduction in the 28-day compressive and splitting tensile strengths was about 14. This study showed that although additional SP can improve the workability of the concrete, it may have a negative effect on the other properties of concrete. Therefore, the SP dosage in concrete mixtures containing PP fiber should be limited to a certain amount.

75 FR 20268 - Implantation or Injectable Dosage Form New Animal Drugs; Change of Sponsor; Propofol

Science.gov (United States)

2010-04-19

... 21 CFR Part 522 Animal drugs. Therefore, under the Federal Food, Drug, and Cosmetic Act and under... use in dogs and cats--(1) Amount. The drug is administered by intravenous injection as follows: (i) Dogs. For induction of general anesthesia without the use of preanesthetics the dosage is 5.5 to 7.0 mg...

A progressive review of Sandhana kalpana (Biomedical fermentation): An advanced innovative dosage form of Ayurveda

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Chaudhary, Anand; Singh, Neetu; Dalvi, Madhuri; Wele, Asmita

2011-01-01

Sandhana kalpana (biomedical fermented formulations) are one of the best dosage forms of Ayurveda in practice since thousands of years. In order to prepare these medicaments, certain sets of conditions are prearranged, which lead to fermentation. Thus, products bequeath with self-generated ethyl alcohol, which potentiate these preparations (Asava–Arishta), pharmaceutically and therapeutically. Commonly, medicinal and commercial components of these formulations are prompting many researchers to contribute in manufacturing, quality control, safety, and efficacy of these formulations. To cope up with this, literature related to Asava–Arishta has been surveyed from the Vedic period to recent publications of Government of India, ie, Ayurvedic Formulary of India, and presented briefly here. In this review paper, we have discussed pioneering facts such as nature and amount of carbohydrate, type of containers, optimum temperature, variety and relevance of initiator of fermentation, manufacturing, regulatory rules, and business aspects of Asava-Arishta. After going through this basic information, any academician or researcher may show a way to further strengthen this dosage form. PMID:22529661

Low-dosage epoetin in maintenance haemodialysis: costs and quality-of-life improvement.

Science.gov (United States)

Harris, D C

1994-01-01

Decisions about epoetin (recombinant human erythropoetin) dosage and target haematocrit in dialysis patients have been determined largely by the high acquisition cost of epoetin, but are made with incomplete knowledge about which target haematocrit gives the optimum clinical benefit. Haematopoietic response to epoetin may be determined by pharmacodynamic factors such as rate and frequency of administration, as well as by individual patient characteristics such as ethnicity. Resistance to epoetin may be due to iron or vitamin deficiency, natural or exogenous inhibitors of erythropoiesis and bone marrow fibrosis. The high acquisition cost of epoetin must be considered along with a number of other factors that can influence the true cost of epoetin treatment. Hidden costs of epoetin treatment include administration costs, changes in other treatments, extra laboratory tests and adverse events. Administration costs and extra laboratory surveillance add little to overall cost. Depletion of iron stores, hypertension, increased blood coagulability and reduced dialyser efficiency resulting from epoetin treatment may all add a small additional component to the true cost. Severe complications with significant cost implications are rare. Amongst the various components of true cost, only the acquisition cost can definitely be reduced by low dosage treatment. Balanced against the true and potential costs of epoetin are a number of benefits which can result in potential savings. The need for blood transfusion is all but abolished, avoiding the cost of transfusion and its complications. Sensitisation against histocompatibility antigens is reduced by avoiding transfusion, and so the waiting time for cadaveric transplantation may be reduced. Rates of hospitalisation for all causes, especially those associated with anaemia, may be reduced by epoetin treatment. By improving well-being, epoetin may allow patients to be transferred to minimal-care units or home where dialysis can be

Development and Statistical Validation of Spectrophotometric Methods for the Estimation of Nabumetone in Tablet Dosage Form

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A. R. Rote

2010-01-01

Full Text Available Three new simple, economic spectrophotometric methods were developed and validated for the estimation of nabumetone in bulk and tablet dosage form. First method includes determination of nabumetone at absorption maxima 330 nm, second method applied was area under curve for analysis of nabumetone in the wavelength range of 326-334 nm and third method was First order derivative spectra with scaling factor 4. Beer law obeyed in the concentration range of 10-30 μg/mL for all three methods. The correlation coefficients were found to be 0.9997, 0.9998 and 0.9998 by absorption maxima, area under curve and first order derivative spectra. Results of analysis were validated statistically and by performing recovery studies. The mean percent recoveries were found satisfactory for all three methods. The developed methods were also compared statistically using one way ANOVA. The proposed methods have been successfully applied for the estimation of nabumetone in bulk and pharmaceutical tablet dosage form.

Effect of low-molecular-weight beta-cyclodextrin polymer on release of drugs from mucoadhesive buccal film dosage forms.

Science.gov (United States)

Arakawa, Yotaro; Kawakami, Shigeru; Yamashita, Fumiyoshi; Hashida, Mitsuru

2005-09-01

We investigated the effect of low-molecular-weight beta-cyclodextrin (beta-CyD) polymer on in vitro release of two drugs with different lipophilicities (i.e., lidocaine and ketoprofen) from mucoadhesive buccal film dosage forms. When beta-CyD polymer was added to hydroxypropylcellulose (HPC) or polyvinylalcohol (PVA) film dosage forms, the release of lidocaine into artificial saliva (pH 5.7) was reduced by 40% of the control. In contrast, the release of ketoprofen from the polymer film was enhanced by addition of beta-CyD polymer to the vehicle. When lidocaine and ketoprofen was incubated with beta-CyD polymer in the artificial saliva, concentration of free lidocaine molecules decreased in a beta-CyD polymer concentration-dependent manner. The association constant with beta-CyD polymer was 6.9+/-0.6 and 520+/-90 M(-1) for lidocaine and ketoprofen, respectively. Retarded release of the hydrophilic lidocaine by beta-CyD polymer might be due to the decrease in thermodynamic activity by inclusion complex formation, whereas enhanced release of the lipophilic ketoprofen by the beta-CyD polymer might be due to prevention of recrystallization occurring after contacting the film with aqueous solution. Thus, effects of low-molecular-weight beta-CyD polymer to the drug release rate from film dosage forms would vary according to the strength of interaction with and the solubility of active ingredient.

PREPARATION AND CHARACTERIZATION OF CO-PROCESSED EXCIPIENT-PREGELATINIZED CASSAVA STARCH PROPIONATE AS A MATRIX IN THE GASTRORETENTIVE DOSAGE FORM

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Junaedi

2011-11-01

Full Text Available The gastroretentive dosage form is designed to prolong the gastric residence time of the drug delivery system whichalso results in the development of an appropriate excipient. The purpose of this study is to develop and characterize coprocessedexcipient made from carrageenan (kappa-iota = 1:1 and pregelatinized cassava starch propionate (PCSP inratios of 1:1, 1:2, and 1:3. PCSP was prepared with propionic anhydride in an aqueous medium. The product was mixedwith carrageenan (kappa-iota = 1:1, as well as characterized physicochemical and functional properties. The coprocessedexcipient was then used as a mucoadhesive granule and floating tablet. The USP Basket was selected toperform the dissolution test of the granules in HCl buffer (pH 1.2 and distilled water for 8 hours each. Mucoadhesiveproperties were evaluated using bioadhesive through a vitro test and wash-off test. As for the floating tablet, the USPPaddle was selected to perform the dissolution test of the tablets in 0.1 N HCl for 10 hours. The floating lag time andfloating time were tested in 0.1 N HCl for 24 hours. The result of these studies indicated that co-processed excipientcarrageenan-PCSP can retard dosage form in gastric and drug controlled release, thus making it a suitable material forthe gastroretentive dosage form.

Oral Solid Dosage Form Disintegration Testing - The Forgotten Test.

Science.gov (United States)

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. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

Maintenance of Xist Imprinting Depends on Chromatin Condensation State and Rnf12 Dosage in Mice.

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Atsushi Fukuda

2016-10-01

Full Text Available In female mammals, activation of Xist (X-inactive specific transcript is essential for establishment of X chromosome inactivation. During early embryonic development in mice, paternal Xist is preferentially expressed whereas maternal Xist (Xm-Xist is silenced. Unlike autosomal imprinted genes, Xist imprinting for Xm-Xist silencing was erased in cloned or parthenogenetic but not fertilized embryos. However, the molecular mechanism underlying the variable nature of Xm-Xist imprinting is poorly understood. Here, we revealed that Xm-Xist silencing depends on chromatin condensation states at the Xist/Tsix genomic region and on Rnf12 expression levels. In early preimplantation, chromatin decondensation via H3K9me3 loss and histone acetylation gain caused Xm-Xist derepression irrespective of embryo type. Although the presence of the paternal genome during pronuclear formation impeded Xm-Xist derepression, Xm-Xist was robustly derepressed when the maternal genome was decondensed before fertilization. Once Xm-Xist was derepressed by chromatin alterations, the derepression was stably maintained and rescued XmXpΔ lethality, indicating that loss of Xm-Xist imprinting was irreversible. In late preimplantation, Oct4 served as a chromatin opener to create transcriptional permissive states at Xm-Xist/Tsix genomic loci. In parthenogenetic embryos, Rnf12 overdose caused Xm-Xist derepression via Xm-Tsix repression; physiological Rnf12 levels were essential for Xm-Xist silencing maintenance in fertilized embryos. Thus, chromatin condensation and fine-tuning of Rnf12 dosage were crucial for Xist imprint maintenance by silencing Xm-Xist.

Cohort-specific imputation of gene expression improves prediction of warfarin dose for African Americans

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Assaf Gottlieb

2017-11-01

Full Text Available Abstract Background Genome-wide association studies are useful for discovering genotype–phenotype associations but are limited because they require large cohorts to identify a signal, which can be population-specific. Mapping genetic variation to genes improves power and allows the effects of both protein-coding variation as well as variation in expression to be combined into “gene level” effects. Methods Previous work has shown that warfarin dose can be predicted using information from genetic variation that affects protein-coding regions. Here, we introduce a method that improves dose prediction by integrating tissue-specific gene expression. In particular, we use drug pathways and expression quantitative trait loci knowledge to impute gene expression—on the assumption that differential expression of key pathway genes may impact dose requirement. We focus on 116 genes from the pharmacokinetic and pharmacodynamic pathways of warfarin within training and validation sets comprising both European and African-descent individuals. Results We build gene-tissue signatures associated with warfarin dose in a cohort-specific manner and identify a signature of 11 gene-tissue pairs that significantly augments the International Warfarin Pharmacogenetics Consortium dosage-prediction algorithm in both populations. Conclusions Our results demonstrate that imputed expression can improve dose prediction and bridge population-specific compositions. MATLAB code is available at https://github.com/assafgo/warfarin-cohort

Peril in the market-classification and dosage of species used as anti-diabetics in Lima, Peru.

Science.gov (United States)

Bussmann, Rainer W; Paniagua-Zambrana, Narel; Chamorro, Marinoli Rivas; Moreira, Natalia Molina; del Rosario Cuadros Negri, María Luisa; Olivera, Jose

2013-05-30

Peru is what Peruvian anthropologist Lupe Camino calls the “health axis” of the old Central Andean culture area stretching from Ecuador to Bolivia. In particular in the North of the country the traditional use of medicinal dates back as far as the first millennium B.C. Both healers, and the wider population, often buy their medicinal plants in local markets, but there is very little comparative information available about which plants are sold under which vernacular name at any given time, for which indication, and which dosage information and information about side effects is given by vendors. For this study we used two traditionally used species groups “Hercampuri” Gentianella spec. (Gentianaceae) and “Pasuchaca” Geranium spec. (Geraniaceae.), found in the Mercado Aviación in Lima, as small, clearly circumscribed plant group frequently used to treat symptoms of diabetes as a test case to study the taxonomy, indications, dosage, indicated side effects, and additional species used as admixtures and hypothesized that: 1. A wide variety of different species is sold under the same common name, and often several common names exist for one species. 2. There is no consistency in the dosage, or a relationship between dosage and species marketed under one name. 3. However, there is consistency in the knowledge about usage and side effects. Surveys focusing on medicinal plants sold and their properties were conducted at the Mercado Aviaciónin Lima in December 2012. Vouchers of all specimens were deposited at the National Herbarium of Peru. Our surveys in Mercado Aviación in Lima yielded four species of Gentianella, two of Geranium, and three additional species from three genera used as common additives that were sold as anti-diabetic. These results indicate that even in case of only a few plant species, used for a very clearly circumscribed application, patients run a considerable risk when purchasing their remedies in the market. The possible side effects in

Genome-wide mapping of furfural tolerance genes in Escherichia coli.

Science.gov (United States)

Glebes, Tirzah Y; Sandoval, Nicholas R; Reeder, Philippa J; Schilling, Katherine D; Zhang, Min; Gill, Ryan T

2014-01-01

Advances in genomics have improved the ability to map complex genotype-to-phenotype relationships, like those required for engineering chemical tolerance. Here, we have applied the multiSCale Analysis of Library Enrichments (SCALEs; Lynch et al. (2007) Nat. Method.) approach to map, in parallel, the effect of increased dosage for >10(5) different fragments of the Escherichia coli genome onto furfural tolerance (furfural is a key toxin of lignocellulosic hydrolysate). Only 268 of >4,000 E. coli genes (∼ 6%) were enriched after growth selections in the presence of furfural. Several of the enriched genes were cloned and tested individually for their effect on furfural tolerance. Overexpression of thyA, lpcA, or groESL individually increased growth in the presence of furfural. Overexpression of lpcA, but not groESL or thyA, resulted in increased furfural reduction rate, a previously identified mechanism underlying furfural tolerance. We additionally show that plasmid-based expression of functional LpcA or GroESL is required to confer furfural tolerance. This study identifies new furfural tolerant genes, which can be applied in future strain design efforts focused on the production of fuels and chemicals from lignocellulosic hydrolysate.

Genome-wide mapping of furfural tolerance genes in Escherichia coli.

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Tirzah Y Glebes

Full Text Available Advances in genomics have improved the ability to map complex genotype-to-phenotype relationships, like those required for engineering chemical tolerance. Here, we have applied the multiSCale Analysis of Library Enrichments (SCALEs; Lynch et al. (2007 Nat. Method. approach to map, in parallel, the effect of increased dosage for >10(5 different fragments of the Escherichia coli genome onto furfural tolerance (furfural is a key toxin of lignocellulosic hydrolysate. Only 268 of >4,000 E. coli genes (∼ 6% were enriched after growth selections in the presence of furfural. Several of the enriched genes were cloned and tested individually for their effect on furfural tolerance. Overexpression of thyA, lpcA, or groESL individually increased growth in the presence of furfural. Overexpression of lpcA, but not groESL or thyA, resulted in increased furfural reduction rate, a previously identified mechanism underlying furfural tolerance. We additionally show that plasmid-based expression of functional LpcA or GroESL is required to confer furfural tolerance. This study identifies new furfural tolerant genes, which can be applied in future strain design efforts focused on the production of fuels and chemicals from lignocellulosic hydrolysate.

Determination of radium in urine; Dosage du radium dans l'urine

Energy Technology Data Exchange (ETDEWEB)

Fourniguet, H; Jeanmaire, L; Jammet, H [Commissariat a l' Energie Atomique, Saclay (France).Centre d' Etudes Nucleaires

1959-07-01

A procedure for the quantitative analysis of radium in urine is described. The radium is carried by a barium sulfate precipitate. The precipitate is mixed with zinc sulfide and the activity measured by scintillation counting. It is thus possible to detect an amount of radium less than 1 pico-curie in the sample. (author) [French] Cet article decrit une technique de dosage du radium dans l'urine. Le radium entraine par un precipite de sulfate de baryum est compte par scintillation apres melange du precipite avec du sulfure de zinc. Cette methode permet de deceler moins de 1 picocurie de radium dans l'echantillon. (auteur)

The presence of mathematics and computer anxiety in nursing students and their effects on medication dosage calculations.

Science.gov (United States)

Glaister, Karen

2007-05-01

To determine if the presence of mathematical and computer anxiety in nursing students affects learning of dosage calculations. The quasi-experimental study compared learning outcomes at differing levels of mathematical and computer anxiety when integrative and computer based learning approaches were used. Participants involved a cohort of second year nursing students (n=97). Mathematical anxiety exists in 20% (n=19) of the student nurse population, and 14% (n=13) experienced mathematical testing anxiety. Those students more anxious about mathematics and the testing of mathematics benefited from integrative learning to develop conditional knowledge (F(4,66)=2.52 at pComputer anxiety was present in 12% (n=11) of participants, with those reporting medium and high levels of computer anxiety performing less well than those with low levels (F(1,81)=3.98 at pmathematical and computer anxiety when planning an educational program to develop competency in dosage calculations.

Enhancement of bioavailability of ketoprofen using dry elixir as a novel dosage form.

Science.gov (United States)

Ahn, H J; Kim, K M; Kim, C K

1998-07-01

To enhance the dissolution rate and bioavailability of poorly water-soluble ketoprofen, a novel oral dosage form of ketoprofen, termed ketoprofen dry elixir, was developed by the spray-drying technique. Ketoprofen, dextrin, and sodium lauryl sulfate were dissolved in an ethanol-water mixture (20:25 w/w) and thereafter spray-dried to form the ketoprofen dry elixir. Comparative studies on the in vitro dissolution and in vivo adsorption of ketoprofen in the form of dry elixir and powder were carried out. Ketoprofen in the dry elixir completely dissolved within 5 min. On the other hand, only about 50.1% of ketoprofen powder alone dissolved during 60 min. The initial dissolution rate of ketoprofen in the dry elixir markedly increased in distilled water at 37 degrees C, becoming fourfold higher than that of ketoprofen powder alone. The maximal plasma concentration of ketoprofen (Cmax) and the area under the concentration-time curve from zero to 8 hr (AUC0-8 hr) after the oral administration of dry elixir increased about 3.2- (24.6 versus 7.6 micrograms/ml) and 2.2-(38.4 versus 17.3 micrograms hr/ml) fold compared with powder alone. It was obvious that ketoprofen dry elixir might be a useful solid dosage form to improve the dissolution rate and bioavailability of poorly water-soluble ketoprofen.

Effect of two dosages of Metarhizium anisopliae var. acridum against Rhammatocerus schistocercoides Rehn

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Faria Marcos Rodrigues de

2002-01-01

Full Text Available The fungus Metarhizium anisopliae var. acridum, strain CG 423, was tested under field conditions against the gregarious grasshopper Rhammatocerus schistocercoides (Rehn (Orthoptera: Acrididae. Conidia formulated in a racemic mixture of soybean oil and kerosene were sprayed under field conditions using an ultralow-volume hand-held atomizer Ulva Plus adjusted to deliver 2.9 L/ha. Bands composed of 2nd instar nymphs were treated with either 5.0x10(12 or 1.0x10(13 viable conidia/ha. The number of insects in each band was estimated at day one following spraying and by the end of the field trial (15 to 16 days post-treatment. Reductions in population size reached, in average, 65.8% and 80.4% for bands treated with the higher and lower dosage, respectively. For both dosages, total mortality rates of insects collected at two days post-application, and kept in cages for 14 days under lab conditions, showed no significant differences as compared to that obtained with insects collected immediately after spraying. Healthy insects were fed to native grasses sprayed on the field with 1.0x10(13 viable conidia/ha. Mortality levels of the nymphs fed on grasses collected two and four days post-application were not affected when compared to nymphs fed on grasses collected immediately following application.

Should we adjust erythropoiesis-stimulating agent dosage to postdialysis hemoglobin levels? A pilot study

OpenAIRE

Castillo Nieves; García-García Patricia; Rivero Antonio; Jiménez-Sosa Alejandro; Macía Manuel; Getino María; Méndez María; García-Pérez Javier; Navarro-González Juan F

2012-01-01

Abstract Background Predialysis hemoglobin (Hb) may overestimate the true erithropoiesis-stimulating agents (ESA) requeriments. We tested whether predialysis Hb is a reliable predictor of the postdialysis level to better control ESA dosage, and evaluated the relation between ESA, Hb and cardiovascular events (CVE). Methods Cohort study including 67 stable hemodialysis patients. Pre- and post-dialysis Hb concentrations were measured, and ESA doses were calculated. A model to predict post-dialy...

Radio-chemical dosage of {sup 90}Sr in large volumes of drinking water; Dosage radiochimique du {sup 90}Sr sur des volumes importants d'eaux potables

Energy Technology Data Exchange (ETDEWEB)

Jeanmaire, L; Patti, F; Bullier, D [Commissariat a l' Energie Atomique, Fontenay-aux-Roses (France). Centre d' Etudes Nucleaires

1965-07-01

I. Principle of the method: 1. Fixing on a resin of all the cations present in the water. 2. Elution using 5 N nitric acid and precipitation of strontium as the carbonate. 3. Concentration of the strontium using the fuming nitric acid method. 4. Purification of the strontium on a resin by selective elution with ammonium citrate. 5. The strontium-90 is measured by separation at the {sup 90}Y equilibrium in the form of the oxalate which is then counted. II. Advantages of the method The concentration of the radio-activity starting from large volumes (100 l) is generally tedious but this method which makes use of a fixation on a cationic resin makes it very simple. The rest of the method consists of a series of simple chemical operations using ion-exchange on resins and coprecipitation. Finally, it is possible to dose stable strontium. (authors) [French] I. Principe du dosage 1. Fixation sur resine de tous les cations presents dans l'eau, 2. Elution par l'acide nitrique 5 N et precipitation du strontium sous forme de carbonate. 3. Concentration du strontium par la methode a l'acide nitrique fumant. 4. Purification du strontium sur resine par elution selective au citrate d'ammonium. 5. Le strontium-90 est dose par separation a l'equilibre du {sup 90}Y sous forme d'oxalate qui est compte. II. Interet de la methode La concentration de la radioactivite a partir de volumes importants (100 l) est generalement fastidieuse, la technique proposee rend cette phase tres simple en utilisant une fixation sur resine cationique. Le reste de la technique est une suite d'operations chimiques simples a realiser, faisant appel a l'echange d'ions sur resine et a la coprecipitation. Enfin, il est possible de realiser le dosage du strontium stable. (auteurs)

Estimating the Optimal Dosage of Sodium Valproate in Idiopathic Generalized Epilepsy with Adaptive Neuro-Fuzzy Inference System

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Somayyeh Lotfi Noghabi

2012-07-01

Full Text Available Introduction: Epilepsy is a clinical syndrome in which seizures have a tendency to recur. Sodium valproate is the most effective drug in the treatment of all types of generalized seizures. Finding the optimal dosage (the lowest effective dose of sodium valproate is a real challenge to all neurologists. In this study, a new approach based on Adaptive Neuro-Fuzzy Inference System (ANFIS was presented for estimating the optimal dosage of sodium valproate in IGE (Idiopathic Generalized Epilepsy patients. Methods: 40 patients with Idiopathic Generalized Epilepsy, who were referred to the neurology department of Mashhad University of Medical Sciences between the years 2006-2011, were included in this study. The function Adaptive Neuro- Fuzzy Inference System (ANFIS constructs a Fuzzy Inference System (FIS whose membership function parameters are tuned (adjusted using either a back-propagation algorithm alone, or in combination with the least squares type of method (hybrid algorithm. In this study, we used hybrid method for adjusting the parameters. Methods: The R-square of the proposed system was %598 and the Pearson correlation coefficient was significant (P 0.05. Although the accuracy of the model was not high, it wasgood enough to be applied for treating the IGE patients with sodium valproate. Discussion: This paper presented a new application of ANFIS for estimating the optimal dosage of sodium valproate in IGE patients. Fuzzy set theory plays an important role in dealing with uncertainty when making decisions in medical applications. Collectively, it seems that ANFIS has a high capacity to be applied in medical sciences, especially neurology.

Materials for Pharmaceutical Dosage Forms: Molecular Pharmaceutics and Controlled Release Drug Delivery Aspects

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Patrick P. DeLuca

2010-09-01

Full Text Available Controlled release delivery is available for many routes of administration and offers many advantages (as microparticles and nanoparticles over immediate release delivery. These advantages include reduced dosing frequency, better therapeutic control, fewer side effects, and, consequently, these dosage forms are well accepted by patients. Advances in polymer material science, particle engineering design, manufacture, and nanotechnology have led the way to the introduction of several marketed controlled release products and several more are in pre-clinical and clinical development.

Differential gene expression profile in pig adipose tissue treated with/without clenbuterol

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Deng Xue M

2007-11-01

Full Text Available Abstract Background Clenbuterol, a beta-agonist, can dramatically reduce pig adipose accumulation at high dosages. However, it has been banned in pig production because people who eat pig products treated with clenbuterol can be poisoned by the clenbuterol residues. To understand the molecular mechanism for this fat reduction, cDNA microarray, real-time PCR, two-dimensional electrophoresis and mass spectra were used to study the differential gene expression profiles of pig adipose tissues treated with/without clenbuterol. The objective of this research is to identify novel genes and physiological pathways that potentially facilitate clenbuterol induced reduction of adipose accumulation. Results Clenbuterol was found to improve the lean meat percentage about 10 percent (P Conclusion Pig fat accumulation was reduced dramatically with clenbuterol treatment. Histological sections and global evaluation of gene expression after administration of clenbuterol in pigs identified profound changes in adipose cells. With clenbuterol stimulation, adipose cell volumes decreased and their gene expression profile changed, which indicate some metabolism processes have been also altered. Although the biological functions of the differentially expressed genes are not completely known, higher expressions of these molecules in adipose tissue might contribute to the reduction of fat accumulation. Among these genes, five lipid metabolism related genes were of special interest for further study, including apoD and apoR. The apoR expression was increased at both the RNA and protein levels. The apoR may be one of the critical molecules through which clenbuterol reduces fat accumulation.

76 FR 25696 - Guidance for Industry on Dosage Delivery Devices for Orally Ingested OTC Liquid Drug Products...

Science.gov (United States)

2011-05-05

... are manufacturing, marketing, or distributing orally ingested over-the-counter (OTC) liquid drug... overdoses that can result from the use of dosage delivery devices with markings that are inconsistent or... because of ongoing concerns about potentially serious accidental drug overdoses that can result from the...

Influence of initial insulin dosage on blood glucose dynamics of children and adolescents with newly diagnosed type 1 diabetes mellitus.

Science.gov (United States)

Wang, Yi; Gong, Chunxiu; Cao, Bingyan; Meng, Xi; Wei, Liya; Wu, Di; Liang, Xuejun; Li, Wenjing; Liu, Min; Gu, Yi; Su, Chang

2017-05-01

To investigate the effect of initial insulin dosage on blood glucose (BG) dynamics, β-cell protection, and oxidative stress in type 1 diabetes mellitus. Sixty newly diagnosed type 1 diabetes mellitus patients were randomly assigned to continuous subcutaneous insulin infusions of 0.6 ± 0.2 IU/kg/d (group 1), 1.0 ± 0.2 IU/kg/d (group 2), or 1.4 ± 0.2 IU/kg/d (group 3) for 3 wk. BG was monitored continuously for the first 10 d and the last 2 d of wk 2 and 3. A total of 24-hour urinary 8-iso-PGF2α was assayed on days 8, 9, and 10. The occurrence and duration of the honeymoon period were recorded. Fasting C-peptide and glycosylated hemoglobin (HbA1c) were assayed after 1, 6, and 12 months of insulin treatment. BG decreased to the target range by the end of wk 3 (group 1), wk 2 (group 2), or wk 1 (group 3). The actual insulin dosage over the 3 wk, frequency of hypoglycemia on wk 1 and 2, and median BG at the end of wk 1 differed significantly, but not 8-iso-PGF2α and the honeymoon period in the three groups. No severe hypoglycemia event was observed in any patient, but there was significant difference in the first occurrence of hypoglycemia. Differences in initial insulin dosage produced different BG dynamics in wk 1, equivalent BG dynamics on wk 2 and 3, but had no influence on short- and long-term BG control and honeymoon phase. The wide range of initial insulin dosage could be chosen if guided by BG monitoring. © 2016 The Authors. Pediatric Diabetes published by John Wiley & Sons Ltd.

Intensive Versus Distributed Aphasia Therapy: A Nonrandomized, Parallel-Group, Dosage-Controlled Study.

Science.gov (United States)

Dignam, Jade; Copland, David; McKinnon, Eril; Burfein, Penni; O'Brien, Kate; Farrell, Anna; Rodriguez, Amy D

2015-08-01

Most studies comparing different levels of aphasia treatment intensity have not controlled the dosage of therapy provided. Consequently, the true effect of treatment intensity in aphasia rehabilitation remains unknown. Aphasia Language Impairment and Functioning Therapy is an intensive, comprehensive aphasia program. We investigated the efficacy of a dosage-controlled trial of Aphasia Language Impairment and Functioning Therapy, when delivered in an intensive versus distributed therapy schedule, on communication outcomes in participants with chronic aphasia. Thirty-four adults with chronic, poststroke aphasia were recruited to participate in an intensive (n=16; 16 hours per week; 3 weeks) versus distributed (n=18; 6 hours per week; 8 weeks) therapy program. Treatment included 48 hours of impairment, functional, computer, and group-based aphasia therapy. Distributed therapy resulted in significantly greater improvements on the Boston Naming Test when compared with intensive therapy immediately post therapy (P=0.04) and at 1-month follow-up (P=0.002). We found comparable gains on measures of participants' communicative effectiveness, communication confidence, and communication-related quality of life for the intensive and distributed treatment conditions at post-therapy and 1-month follow-up. Aphasia Language Impairment and Functioning Therapy resulted in superior clinical outcomes on measures of language impairment when delivered in a distributed versus intensive schedule. The therapy progam had a positive effect on participants' functional communication and communication-related quality of life, regardless of treatment intensity. These findings contribute to our understanding of the effect of treatment intensity in aphasia rehabilitation and have important clinical implications for service delivery models. © 2015 American Heart Association, Inc.

Laboratory data of serum triiodothyronine, thyroxine and thyrotrophin dosages for diagnosis of primary hypothyroidism

International Nuclear Information System (INIS)

Nicolau, W.; Abelin, N.M.A.; Villares, S.M.; Mattar, E.

1984-01-01

TSH dosages are studied in 5.598 patients during 31 months. TSH values equal or superior than 10 μlU/ml was chosen (360 samples). These ones, 193 presented T 3 and T 4 results changed, too. The several factors that could influence the normal peripheral levels of T 3 and T 4 in primary hypothyroidal patients and the factors that cause an eventual low correlation with TSH are discussed. (M.A.C.) [pt

Investigation of radiation exposure dosage in dental and panoramic radiography

International Nuclear Information System (INIS)

Ishii, Kenichi

2005-01-01

Dental radiography and a 10-sheet procedure were conducted at 10 sites in the maxillomandibular anterior teeth and at both sides of the premolar and molar teeth sections with and without a protective apron (total 22 patterns). Experiments, which included a total of five patterns, involving standard ortho-radiography were performed with and without a protective apron, positioning of an apron exclusively on the anterior or the posterior portion of the body and utility of an apron that covered the entire body. Results are as follows: In dental radiography, internal organs included in a bundle demonstrated high radiation exposure, whereas organs excluded from the bundle exhibited low radiation exposure. In organs situated below the thyroid gland, utilization of aprons resulted in lower radiation exposure. In ortho-radiography, radiation exposure was greatest in the parotid gland, followed by the mandibular, sublingual and thyroid glands, respectively. The protective apron resulted in lower radiation exposure at sites situated below the mammary glands; moreover, a protector covering the entire body led to lower radiation exposure in comparison to an apron worn exclusively on the anterior or the posterior aspect of the body. No significant difference was observed in terms of exposure between protective aprons worn on the anterior or the posterior aspect of the body. Furthermore, a protective collar resulted in nearly zero radiation exposure in the thyroid gland. However, a protective collar largely interferes with interpretation of the radiograph; thus, in order to produce interpretable radiographs, protection of the thyroid gland is not possible. In conclusion, radiation exposure dosage can be reduced via utilization of a protective apron positioned below the thyroid gland during dental radiography and below the mammary glands during ortho-radiography. We confirmed evidence indicating that application of a protective apron can reduce patient radiation exposure dosage

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

Science.gov (United States)

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

2014-02-01

Literature and experimental data relevant to the decision to allow a waiver of in vivo bioequivalence (BE) testing for the approval of immediate release (IR) solid oral dosage forms containing piroxicam in the free acid form are reviewed. Piroxicam solubility and permeability, its therapeutic use and therapeutic index, pharmacokinetic properties, data related to the possibility of excipient interactions and reported BE/bioavailability (BA), and corresponding dissolution data are taken into consideration. The available data suggest that according to the current biopharmaceutics classification system (BCS) and all current guidances, piroxicam would be assigned to BCS Class II. The extent of piroxicam absorption seems not to depend on manufacturing conditions or excipients, so the risk of bioinequivalence in terms of area under the curve (AUC) is very low, but the rate of absorption (i.e., BE in terms of Cmax ) can be affected by the formulation. Current in vitro dissolution methods may not always reflect differences in terms of Cmax for BCS Class II weak acids; however, minor differences in absorption rate of piroxicam would not subject the patient to unacceptable risks: as piroxicam products may be taken before or after meals, the rate of absorption cannot be considered crucial to drug action. Therefore, a biowaiver for IR piroxicam solid oral dosage form is considered feasible, provided that (a) the test product contains only excipients, which are also present in IR solid oral drug products containing piroxicam, which have been approved in ICH or associated countries, for instance, those presented in Table 3 of this paper; (b) both the test and comparator drug products dissolve 85% in 30 min or less at pH 1.2, 4.5, and 6.8; and (c) the test product and comparator show dissolution profile similarity in pH 1.2, 4.5, and 6.8. When not all of these conditions can be fulfilled, BE of the products should be established in vivo. © 2013 Wiley Periodicals, Inc. and the

Effect of Slag Content and Hardening Accelerator Dosage on the Physico Mechanical Properties of Cement and Concrete

International Nuclear Information System (INIS)

Derabla, R.; Mokrani, I.; Benmalek, M.L.

2011-01-01

Our contribution consists at the study of the effect of (0 %, 0.2 % and 0.34 %) dosage of an hardening accelerating plasticizer (Plastocrete 160, produced by Sika Aldjazair) on the properties of normal mortar and concretes prepared with portland cement artificial of Hadjar Soud cement factory (Skikda - Algeria) with addition of (10 % and 20 %) of granulated blast furnace slag finely crushed of the El Hadjar blast furnace (Annaba - Algeria). The tests are focused to the physical and mechanical characteristics of elaborated materials to knowing: setting time, porosity, water absorption capacity and the test of compressive strength at 2, 7 and 28 days. The results obtained show clearly the reliability of the additive used to accelerate the hardening and to obtain high strengths at early age, which increase by increasing of the additive dosage. For the slag, its low hydraulic capacity does not make it profitable than at the long term (beyond 28 days). (author)

PDV2 has a dosage effect on chloroplast division in Arabidopsis.

Science.gov (United States)

Chang, Ning; Sun, Qingqing; Li, Yiqiong; Mu, Yajuan; Hu, Jinglei; Feng, Yue; Liu, Xiaomin; Gao, Hongbo

2017-03-01

PDV2 has a dosage effect on chloroplast division in Arabidopsis thaliana , but this effect may vary in different plants. Chloroplasts have to be divided as plants grow to maintain an optimized number in the cell. Chloroplasts are divided by protein complexes across the double membranes from the stroma side to the cytosolic side. PDV2 is a chloroplast division protein on the chloroplast outer membrane. It recruits the dynamin-related GTPase ARC5 to the division site. The C-terminus of PDV2 and the C-terminus of ARC6 interact in the intermembrane space, which is important for the localization of PDV2. Previously, it was shown that overexpression of PDV2 can increase the division of chloroplasts in Arabidopsis and moss, so the authors concluded that PDV2 determines the rate of chloroplast division in land plants. PDV2 was also shown to inhibit the GTPase activity of ARC5 by in vitro experiment. These results look to be contradictory. Here, we identified a null allele of PDV2 in Arabidopsis and studied plants with different levels of PDV2. Our results suggested that the chloroplast division phenotype in Arabidopsis is sensitive to the level of PDV2, while this is not the case for ARC6. The level of PDV2 protein is reduced sharply in fast-growing leaves, while the level of ARC6 is not. The levels of PDV2 and ARC6 in several other plant species at different developmental stages were also investigated. The results indicated that their expression pattern varies in different species. Thus, PDV2 is an important positive factor of chloroplast division with an apparent dosage effect in Arabidopsis, but this effect for different chloroplast division proteins in different plants may vary.

Dosing of traces of oxygenated water by polarography; Dosage de traces d'eau oxygenee par polarographie

Energy Technology Data Exchange (ETDEWEB)

Faure, A. M.; Malterre, J.

1960-07-01

As dosing oxygenated water by using polarography has been envisaged within the framework of water purity controls for the Melusine pile, the objective of the authors is here to see whether the polarographic method could be satisfying for routine analyses, and would result in a higher dosing sensitivity. They describe the polarography principle, indicate devices which are used, specify and comment conditions under which polarography is performed [French] Le dosage de l'eau oxygenee par polarographie a ete envisage dans le cadre des controles de purete de l'eau de la pile Melusine. La methode calorimetrique dans les conditions de fonctionnement de Melusine a puissance maxima, avait mis en evidence des teneurs en H{sub 2}O{sub 2} produites par radiolyse de l'eau, inferieures a 20 ppm. Le but de cette etude, a ete de voir si la methode polarographique pouvait donner satisfaction en analyse de routine a ces teneurs la et permettre une plus grande sensibilite de dosage, la colorimetrie se limitant pratiquement a 1 ppm avec une precision de 20 pour cent environ. (auteurs)

Differential expression of photosynthesis-related genes in pentaploid interspecific hybrid and its decaploid of Fragaria spp.

Science.gov (United States)

Wang, Tao; Huang, Dongya; Chen, Baoyu; Mao, Nini; Qiao, Yushan; Ji, Muxiang

2018-03-01

Polyploidization always induces a series of changes in genome, transcriptome and epigenetics, of which changes in gene expression are the immediate causes of genotype alterations of polyploid plants. In our previous study on strawberry polyploidization, genes related to photosynthesis were found to undergo changes in gene expression and DNA methylation. Therefore, we chose 11 genes that were closely related to plant photosynthesis and analysed their expression during strawberry hybridization and chromosome doubling. Most genes of pentaploids showed expression levels between parents and were more similar to F. × ananassa. Gene expression levels of decaploids were higher than those of pentaploids and F. × ananassa. Different types of photosynthesis-related genes responded differently to hybridization and chromosome doubling. Chloroplast genes and regulatory genes showed complex responses. Structural genes of the photosynthetic system were expressed at a constant level and displayed a clear dosage effect. The methylation levels of one CG site on SIGE, which regulates expression of chloroplast genes, were negatively correlated with gene expression. In pentaploids and decaploids, more transcripts were from F. × ananassa than from F. viridis. The ratio of transcripts from from F. × ananassa to those from F. viridis was close to the ratio (4:1) of the genome of F. × ananassa to that of F. viridis in pentaploids and decaploids, but there were also some exceptions with obvious deviation.

Human SOD1 ALS Mutations in a Drosophila Knock-In Model Cause Severe Phenotypes and Reveal Dosage-Sensitive Gain- and Loss-of-Function Components.

Science.gov (United States)

Şahin, Aslı; Held, Aaron; Bredvik, Kirsten; Major, Paxton; Achilli, Toni-Marie; Kerson, Abigail G; Wharton, Kristi; Stilwell, Geoff; Reenan, Robert

2017-02-01

Amyotrophic Lateral Sclerosis (ALS) is the most common adult-onset motor neuron disease and familial forms can be caused by numerous dominant mutations of the copper-zinc superoxide dismutase 1 (SOD1) gene. Substantial efforts have been invested in studying SOD1-ALS transgenic animal models; yet, the molecular mechanisms by which ALS-mutant SOD1 protein acquires toxicity are not well understood. ALS-like phenotypes in animal models are highly dependent on transgene dosage. Thus, issues of whether the ALS-like phenotypes of these models stem from overexpression of mutant alleles or from aspects of the SOD1 mutation itself are not easily deconvolved. To address concerns about levels of mutant SOD1 in disease pathogenesis, we have genetically engineered four human ALS-causing SOD1 point mutations (G37R, H48R, H71Y, and G85R) into the endogenous locus of Drosophila SOD1 (dsod) via ends-out homologous recombination and analyzed the resulting molecular, biochemical, and behavioral phenotypes. Contrary to previous transgenic models, we have recapitulated ALS-like phenotypes without overexpression of the mutant protein. Drosophila carrying homozygous mutations rendering SOD1 protein enzymatically inactive (G85R, H48R, and H71Y) exhibited neurodegeneration, locomotor deficits, and shortened life span. The mutation retaining enzymatic activity (G37R) was phenotypically indistinguishable from controls. While the observed mutant dsod phenotypes were recessive, a gain-of-function component was uncovered through dosage studies and comparisons with age-matched dsod null animals, which failed to show severe locomotor defects or nerve degeneration. We conclude that the Drosophila knock-in model captures important aspects of human SOD1-based ALS and provides a powerful and useful tool for further genetic studies. Copyright © 2017 by the Genetics Society of America.

Effects of different dosages of propylene glycol in dry cows and cows in early lactation.

Science.gov (United States)

Maurer, Michaela; Peinhopf, Walter; Gottschalk, Jutta; Einspanier, Almut; Koeller, Gabor; Wittek, Thomas

2017-11-01

In this Research Paper we hypothesised that the temporary insulin resistance seen during the transition period in dairy cows may cause significant differences in the efficacy of PG at different sampling periods and that in some cases this effect will be dose dependent. Eighty four sampling sets were generated by studying 7 multiparous Holstein cows repeatedly at 4 sampling periods of 3 d length (dry cows: days 40, 39 and 38 antepartum; close up cows: days 10, 9 and 8 antepartum; fresh cows: days 3, 4 and 5 post-partum; lactating cows: days 38, 39 and 40 post-partum). On each of these days 3 h after morning feeding propylene glycol was drenched in different dosages of 100, 300 or 500 ml once per day (cross over study). The different doses were applied in an alternating order (Latin square). Blood samples were taken before, every 30 min up to 4 h, after 6 and 12 h after PG application. Following parameters have been measured: insulin, non-esterified fatty acids (NEFA), betahydroxybutyrate (BHB), bilirubin, cholesterol, potassium, aspartate aminotransferase (AST) and glutamate dehydrogenase (GLDH). Revised Quantitative Insulin Sensitivity Check Index (RQUICKI) was calculated. It was found that glucose, insulin, NEFA, BHB, bilirubin and potassium concentrations were influenced differently by the three defined dosages of propylene glycol at four different sampling periods. Whereas RQUICKI, cholesterol, AST and GLDH did not differ between the sampling periods and treatments. The major results of the study are that the effect of PG is dose-dependent and that the effect of PG is depending on the time of application according to calving. It can be concluded that in fresh cows higher dosages are necessary to provoke similar effects in comparison to dry, close up and lactating cows. Although the study did not compare to topdressing of PG from the results it is reasonable to believe that bolus application of a specific PG volume is necessary to provoke the effect.

Microstructural effects in drug release by solid and cellular polymeric dosage forms: A comparative study.

Science.gov (United States)

Blaesi, Aron H; Saka, Nannaji

2017-11-01

In recent studies, we have introduced melt-processed polymeric cellular dosage forms to achieve both immediate drug release and predictable manufacture. Dosage forms ranging from minimally-porous solids to highly porous, open-cell and thin-walled structures were prepared, and the drug release characteristics investigated as the volume fraction of cells and the excipient molecular weight were varied. In the present study, both minimally-porous solid and cellular dosage forms consisting of various weight fractions of Acetaminophen drug and polyethylene glycol (PEG) excipient are prepared and analyzed. Microstructures of the solid forms and the cell walls range from single-phase solid solutions of the excipient and a small amount of drug molecules to two-phase composites of the excipient and tightly packed drug particles. Results of dissolution experiments show that the minimally-porous solid forms disintegrate and release drug by slow surface erosion. The erosion rate decreases as the drug weight fraction is increased. By contrast, the open-cell structures disintegrate rapidly by viscous exfoliation, and the disintegration time is independent of drug weight fraction. Drug release models suggest that the solid forms erode by convective mass transfer of the faster-eroding excipient if the drug volume fraction is small. At larger drug volume fractions, however, the slower-eroding drug particles hinder access of the free-flowing fluid to the excipient, thus slowing down erosion of the composite. Conversely, the disintegration rate of the cellular forms is limited by diffusion of the dissolution fluid into the excipient phase of the thin cell walls. Because the wall thickness is of the order of the drug particle size, and the particles are enveloped by the excipient during melt-processing, the drug particles cannot hinder diffusion through the excipient across the walls. Thus the disintegration time of the cellular forms is mostly unaffected by the volume fraction of drug

Altered expression of mitochondrial and extracellular matrix genes in the heart of human fetuses with chromosome 21 trisomy

Directory of Open Access Journals (Sweden)

Olla Carlo

2007-08-01

Full Text Available Abstract Background The Down syndrome phenotype has been attributed to overexpression of chromosome 21 (Hsa21 genes. However, the expression profile of Hsa21 genes in trisomic human subjects as well as their effects on genes located on different chromosomes are largely unknown. Using oligonucleotide microarrays we compared the gene expression profiles of hearts of human fetuses with and without Hsa21 trisomy. Results Approximately half of the 15,000 genes examined (87 of the 168 genes on Hsa21 were expressed in the heart at 18–22 weeks of gestation. Hsa21 gene expression was globally upregulated 1.5 fold in trisomic samples. However, not all genes were equally dysregulated and 25 genes were not upregulated at all. Genes located on other chromosomes were also significantly dysregulated. Functional class scoring and gene set enrichment analyses of 473 genes, differentially expressed between trisomic and non-trisomic hearts, revealed downregulation of genes encoding mitochondrial enzymes and upregulation of genes encoding extracellular matrix proteins. There were no significant differences between trisomic fetuses with and without heart defects. Conclusion We conclude that dosage-dependent upregulation of Hsa21 genes causes dysregulation of the genes responsible for mitochondrial function and for the extracellular matrix organization in the fetal heart of trisomic subjects. These alterations might be harbingers of the heart defects associated with Hsa21 trisomy, which could be based on elusive mechanisms involving genetic variability, environmental factors and/or stochastic events.

Stability-indicating HPLC determination of pramipexole dihydrochloride in bulk drug and pharmaceutical dosage form

OpenAIRE

Panditrao, Vedavati M; Sarkate, Aniket P; Sangshetti, Jaiprakash N; Wakte, Pravin S; Shinde, Devanand B

2011-01-01

A novel stability-indicating high-performance liquid chromatographic assay method was developed and validated for quantitative determination of pramipexole dihydrochloride in bulk drugs and in pharmaceutical dosage form in the presence of degradation products. An isocratic, reversed phase HPLC method was developed to separate the drug from the degradation products, using an Ace5-C18 (250×4.6 mm, 5 µm) advance chromatography column, and 10 mmol L-1 ammonium acetate and acetonitrile (75:25 v/v)...

Development of Direct Reversed-Phase High Performance liquid chromatographic method for quantitative determination of gabapentin in pharmaceutical dosage

International Nuclear Information System (INIS)

Hassan, W.; Zaman, B.; Rahman, S.; Rahman, A.U.; Ali, N.; Mohammadzai, I.U.

2012-01-01

The objective of the present work was to develop and validate a rapid analytical method for quantitative determination of Gabapentin in pharmaceutical dosage tablets and capsules. An accurate, simple, and sensitive reversed-phase high performance liquid chromatographic (HPLC) method, UV detection at 215 nm and flow rate at 1.0 ml/min has been developed. Isocratic elution was used instead of gradient elution to reduce the time and cost of serial analysis. The mobile phase was a mixture of water and methanol (HPLC grade). The retention time (Rt) of Gabapentin was 4.681 +- 0.013 minutes. Recovery, Precision, accuracy, and linearity were determined for the stated method. The calibration curve was linear and the correlation coefficient was 0.9996. There was no chromatographic interference from other excipients present in dosage form. The method was validated appropriately and successfully used for determination of Gabapentin in Pharmaceutical formulations. (author)

HPLC DETERMINATION OF FENBENDAZOLE AND IVERMECTIN SIMULTANEOUSLY IN BULK AND PHARMACEUTICAL DOSAGE FORMS

OpenAIRE

Battula Sreenivasa Rao, Mandapati Varaprasad Reddy*, Bhatraju Sreenivasa Rao

2017-01-01

In the present study, a simple, precise and accurate high performance liquid chromatography with photodiode array detector was developed for the simultaneous estimation of ivermectin & fenbendazole in bulk and tablet dosage forms. A Zorbax C8 column (250 cm × 4.6 mm × 5 μm) with mobile phase consisting of 0.1 M potassium dihydrogen orthophosphate and methanol (60:40 v/v) having pH 4.5 (adjusted with orthophosphoric acid) was used. The flow rate was 1.2 ml/min and the effluents were detected a...

COMPARISON OF PHYSICAL STABILITY PROPERTIES OF POMEGRANATE SEED OIL NANOEMULSION DOSAGE FORMS WITH LONG-CHAIN TRIGLYCERIDE AND MEDIUM-CHAIN TRIGLYCERIDE AS THE OIL PHASE

Directory of Open Access Journals (Sweden)

Sri Hartanti Yuliani

2016-08-01

Full Text Available Pomegranate seed oil has antioxidant, anti-inflammatory, and chemo preventive activities. Pomegranate seed oil is lipophilic substance suitable to be prepared in emulsion dosage forms. Long-chain triglyceride (LCT and medium-chain triglyceride (MCT are commonly used as oil phase in emulsion dosage forms. This research aimed to compare the use of LCT and MCT in the Nano emulsion formula of pomegranate seed oil dosage forms. Formulation of pomegranate seed oil Nano emulsion was conducted using high energy emulsification. Parameters observed were pH, Nano emulsion type, percent transmittance, viscosity, turbidity, and droplet size before and after 3 cycles of freeze-thaw. The result showed that there was no significant difference between physical properties of pomegranate oil Nano emulsion with LCT as oil phase and pomegranate oil Nano emulsion with MCT as oil phase. Moreover, physical stability of pomegranate oil Nano emulsion with LCT as oil phase was better than pomegranate oil Nano emulsion with MCT as oil phase.

Performance of Nile tilapia juvenile fed diet containing different dosages ofrecombinant common carpgrowth hormone

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Dian Hardiantho

2013-11-01

Full Text Available The studywas conductedtodetermine thedose of recombinant common carp growth hormone (rCcGH supplemented in the commercial diet that generates the best performanceonbodyweight, biomass, andfeed conversion rate of juvenile tilapia.The dose of rCcGH administered was10, 20, and30mg/kg of commercial feed, andnorGH supplementation as control. Eachtreatment was designed in triplicates. Juveniles at average bodylengthof about2cm(average body weight of 0.7 g were reared in a density of25fish/m2, for three weeks in hapa net at a size of 2×2×1 m3. Fish were fed diet containing rCcGH twicea week with an interval ofthreedays. The juvenile were fed with the rCcGH supplemented diet three times daily at satiation. The results showedthat average body weight andbiomass of fish treated by rCcGH with the doses of 20 and 30 mg/kg feed was higher (p<0.05 than that of 10 mg/kg and control. In addition, feed conversionrate of 20 and 30 mg/kg feed treatments was lower (p<0.05 than that of 10 mg/kg and control. RT-PCR analysisshowedthat expression level of IGF-1 gene in juvenile liver was increased in parallel with the increasing of rCcGH dosages supplemented in diet.This suggestedthatIGF-1 plays an important rolein the induction ofgrowth,andfeed conversionefficiencyof tilapiafed diet containing rCcGH. The bestperformance of juvenile can be obtainedby feeding with diet containingrCcGH20‒30mg/kgof feed. Keywords: rCcGH, IGF-I, recombinant growthhormone,performance, Nile tilapia.

Consumer Preferences and Perceptions towards the use Colored Oral Solid Dosage Forms in Baghdad

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Inas Rifaat Ibrahim,*, Mohamed Izham M.I & Mahmoud Al-Haddad

2010-10-01

Full Text Available Objective: The main aims of this study were to determine consumers’ preferences and perceptions in Baghdad towards the color of Oral Solid Dosage Form.Materials and Methods: A cross sectional study was conducted using a self–administered questionnaire. A convenient sampling method was adopted to approach the consumers visiting the community pharmacies in Baghdad.The data collected was analyzed using SPSS version 16 ®. Anon-parametric statistics i.e [Chi-square, Mann-Whitney and Kruskal-Wallis tests] were used to evaluate the association of demographic variables with respondents perceptions toward physical characteristics of Oral Solid Dosage Form.Results: Colored OSDF was preferred by 76.4% of consumers.Significant differences in this preference were found among genders (P=0.029; age (P<0.001; educational level (P=0.001;and monthly income level (0.007. Further, consumers perceived that color of OSDF is related with the therapeutic activity of medicine. Significant differences in this perception were found to be influenced by gender (P=0.016; age group(P<0.001; and educational level (P<0.001.Conclusion: In a conclusion, color was the most preferred characteristic of OSDF by Baghdadi consumers with the perceptions that color is related to therapeutic activity of medicines. Gender, age, educational level, and monthly income are important factors that are associated with the preferences and perceptions toward colored OSDF.

Spectrophotometric method for simultaneous estimation of atazanavir sulfate and ritonavir in tablet dosage form

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Disha A Patel

2015-01-01

Full Text Available Background: Ritonavir (RTV and atazanavir sulfate (ATV are protease inhibitor and RTV mostly used as a booster for increasing the bioavailability of other protease inhibitors like ATV. Aims: Quality assessment of the new dosage form of RTV and ATV i.e., tablets is very essential and hence this work deals with to develop sensitive, simple and precise method for simultaneous estimation of ATV and RTV in tablet dosage form by absorbance correction method. Materials and Methods: The present work was carried out on Shimadzu Ultraviolate(UV-1700 double beam spectrophotometer with 1 cm path length supported by S Shimadzu, model-1700(Japan, UV-Probe software, version 2.31 was used for spectral measurements with 10 mm matched quartz cells. Standard ATV and RTV were supplied by Cipla Pharmaceutical Ltd. Methanol was purchased from Finar Chemicals Pvt. Ltd. Results and Conclusion: The λmax or the absorption maxima for ATV and RTV were found to be 279 and 240 nm, respectively in methanol as solvent. The drugs follow Beer-Lambert′s law in the concentration range 30-90 and 10-30 μg/mL for ATV and RTV, respectively. The percentage recovery was found to be 100-100.33% and 100-101.5% for ATV and RTV, respectively. The method was validated for different parameters as per the International Conference for Harmonization Guidelines.

An efficient parallel stochastic simulation method for analysis of nonviral gene delivery systems

KAUST Repository

Kuwahara, Hiroyuki

2011-01-01

Gene therapy has a great potential to become an effective treatment for a wide variety of diseases. One of the main challenges to make gene therapy practical in clinical settings is the development of efficient and safe mechanisms to deliver foreign DNA molecules into the nucleus of target cells. Several computational and experimental studies have shown that the design process of synthetic gene transfer vectors can be greatly enhanced by computational modeling and simulation. This paper proposes a novel, effective parallelization of the stochastic simulation algorithm (SSA) for pharmacokinetic models that characterize the rate-limiting, multi-step processes of intracellular gene delivery. While efficient parallelizations of the SSA are still an open problem in a general setting, the proposed parallel simulation method is able to substantially accelerate the next reaction selection scheme and the reaction update scheme in the SSA by exploiting and decomposing the structures of stochastic gene delivery models. This, thus, makes computationally intensive analysis such as parameter optimizations and gene dosage control for specific cell types, gene vectors, and transgene expression stability substantially more practical than that could otherwise be with the standard SSA. Here, we translated the nonviral gene delivery model based on mass-action kinetics by Varga et al. [Molecular Therapy, 4(5), 2001] into a more realistic model that captures intracellular fluctuations based on stochastic chemical kinetics, and as a case study we applied our parallel simulation to this stochastic model. Our results show that our simulation method is able to increase the efficiency of statistical analysis by at least 50% in various settings. © 2011 ACM.

Determination of some histamine H1-receptor antagonists in dosage forms.

Science.gov (United States)

Gazy, Azza A; Mahgoub, Hoda; El-Yazbi, F A; El-Sayed, M A; Youssef, Rasha M

2002-10-15

Three simple and accurate methods are presented for determination of Cetirizine, Fexofenadine, Loratadine and Acrivastine in pure form and commercial dosage forms. The first method is based on the reaction of the above cited drugs with bromocresol purple dye to form ion-pair complex extractable with chloroform and subsequently measured spectrophotometrically. Secondly, eosin gives with these drugs ion-pair complex, measurable directly without extraction both spectrophotometrically and spectrofluorimetrically. The last method involves the base-catalysed condensation of mixed anhydrides of organic acids (citric acid/acetic anhydride) where as the tertiary amino group in the above-cited drugs acts as the basic catalyst. The product of condensation is measured spectrophotometrically. All the reaction conditions for the proposed methods have been studied. Copyright 2002 Elsevier Science B.V.

[Pharmaceutical counseling of non-conventional dosage forms concerning the health-literacy and the patient adherence in public medication dispensing -Questionnaire surveys in Hungarian community pharmacies.

Science.gov (United States)

Somogyi, O; Zelko, R

Although the non-conventional dosage forms (e.g. modified release per oral systems or transdermal patches) have more significant advantages than other conventional dosage forms, the pa- tients have to apply them correctly in their home medicine using to reach the effective and safe therapy. A guideline of relevant application instructions contribute to development of an effective pharmaceutical counseling in community pharmacies. The counseling and advices can improve the patients' knowledge concerning application rules of different new dosage forms (health- literacy) with patient adherence. Finally it will result more effective and safer therapies. The aim of our Hungarian questionnaire surveys was to explore the patients' drug application habits or application errors and improve special verbal counseling of mentioned non-conventional dosage forms in community pharmacies. Understandable patient information leaflets were developed about application rules and besides the levels of patients' reading comprehension was evaluated in case of the leaflet of medicinal patches. The results show that a properly developed text is useful for the majority of patients but they need the verbal explanation as well, moreover there is a demand for the verbal counseling in community pharmacies. The most common application errors were explored and the most effective instructions or application rules were collected for the pharmacists and patients concerning the modified release tablets or capsules and transdermal patches.

75 FR 13766 - Guidance for Industry on the Content and Format of the Dosage and Administration Section of...

Science.gov (United States)

2010-03-23

...] (formerly Docket No. 2007D-0118) Guidance for Industry on the Content and Format of the Dosage and... Labeling for Human Prescription Drug and Biological Products--Content and Format.'' This guidance is one of... the final rule on the content and format of labeling for [[Page 13767

The histone genes in HeLa cells are on individual transcriptional units

International Nuclear Information System (INIS)

Hackett, P.B.; Traub, P.; Gallwitz, D.

1978-01-01

The distances of the five major histone genes from their promotors have been investigated in order to determine whether in human cells these genes could be transcribed as a single polycistronic transcriptional unit. By measuring the decreases of both histone protein and histone mRNA synthesis as functions of the ultraviolet light dosage, it was possible to calculate the distances of the histone genes from their promotors. The inactivation kinetics for histone genes H1 and H3 are first-order, indicating a single type of transcriptional unit for each gene. The dose-response kinetics for genes H2A, H2B and H4 are first-order with two distinct rates; 10 to 15% of the genes for each of these histones appear to be much more sensitive to ultraviolet light inactivation than are the majority. It is concluded that the transcriptional units for 85 to 90% of the genes for H2A, H2B and H4 are similar. As determined by the inhibition of protein synthesis, the inactivation coefficients for the major component of each histone are: H1, 907 mm 2 /erg; H2A, 878 mm 2 /erg; H2B, 871 mm 2 /erg; H3, 965 mm 2 /erg; and H4, 792 mm 2 /erg. The sensitivities of histone mRNA synthesis to irradiation were measured by translation in vitro with similar results. The calculated target sizes for the genes (in base-pairs) are: H1, 1190; H2A, 1240; H2B, 1250; H3, 1130; and H4, 1380. This similarity in target sizes for all five of the histones genes indicates that they are primarily transcribed from individual transcriptional units. (author)

Clinical Effects of Lithospermum Ruderale Dosage and Using-time on Medicinal Abortion Induced by Mifepris tone and Misoprostol

Institute of Scientific and Technical Information of China (English)

无

2000-01-01

The clinical effects of dosage during the period of treatment of Lithospermum Ruderale extract-a kind of Chinese traditional herbal medicine-on medicinal abor tion induced by mifepristone and misoprostol were studied. Lithospermum Ruderale extract was administrated 3 d before, 3 d after or 3 d before plus 3 d after the admin istration of misoprostol respectively. The dose of Lithospermum Ruderale extract was 50 g, 75 g or 100g respectively. Thus 1 350 women of early pregnancy were grouped into 9 groups and observed. The results showed that the effects of Lithospermum Rud erale used 3 d before, and 3 d before plus 3 d after (6 days misoprostol were signifi cantly better than those only used 3 d after misoprostol both for complete abortion and bleeding (P＜0.05). The dosage between 50 g and l00 g made no significant differ ence in clinical effects. Therefore it is reasonable to use 50 g Lithospermum Ruderale before misoprostol to improve medicinal abortion.

Pre-anthesis CPPU low dosage application increases 'Hayward' kiwifruit weight without affecting the other qualitative and nutritional characteristics.

Science.gov (United States)

Cruz-Castillo, J G; Baldicchi, A; Frioni, T; Marocchi, F; Moscatello, S; Proietti, S; Battistelli, A; Famiani, F

2014-09-01

In 2008, in Central Italy, a low dosage of CPPU solution, 4 μL L(-1) (6 hL/ha), was sprayed on the canopy of vines of 'Hayward' kiwifruit, at the "break of sepals", about one week before anthesis, to study its effects on fruit weight/size and on qualitative and nutritional characteristics. At harvest, CPPU, with respect to control, significantly increased the fresh weight by about 12% (+12.6 g fruit(-1)) and consequently the yield per vine, without affecting fruit shape, firmness, dry matter (%), total soluble solids, glucose, fructose, sucrose, starch, citrate, malate, vitamin C and soluble and insoluble oxalic acid. After 3 months of storage, CPPU-treated kiwifruits and the control fruit showed no difference in dry matter content, fruit firmness and total soluble solids. The results indicate that a low dosage of CPPU applied in pre-anthesis can improve fruit weight/size without any negative effect on fruit qualitative and nutritional characteristics. Copyright © 2014 Elsevier Ltd. All rights reserved.

New Spectrophotometric and Conductometric Methods for Macrolide Antibiotics Determination in Pure and Pharmaceutical Dosage Forms Using Rose Bengal

Directory of Open Access Journals (Sweden)

Rania A. Sayed

2013-01-01

Full Text Available Two Simple, accurate, precise, and rapid spectrophotometric and conductometric methods were developed for the estimation of erythromycin thiocyanate (I, clarithromycin (II, and azithromycin dihydrate (III in both pure and pharmaceutical dosage forms. The spectrophotometric procedure depends on the reaction of rose bengal and copper with the cited drugs to form stable ternary complexes which are extractable with methylene chloride, and the absorbances were measured at 558, 557, and 560 nm for (I, (II, and (III, respectively. The conductometric method depends on the formation of an ion-pair complex between the studied drug and rose bengal. For the spectrophotometric method, Beer's law was obeyed. The correlation coefficient ( for the studied drugs was found to be 0.9999. The molar absorptivity (, Sandell’s sensitivity, limit of detection (LOD, and limit of quantification (LOQ were also calculated. The proposed methods were successfully applied for the determination of certain pharmaceutical dosage forms containing the studied drugs

Caffeine inhibits gene conversion by displacing Rad51 from ssDNA

Science.gov (United States)

Tsabar, Michael; Mason, Jennifer M.; Chan, Yuen-Ling; Bishop, Douglas K.; Haber, James E.

2015-01-01

Efficient repair of chromosomal double-strand breaks (DSBs) by homologous recombination relies on the formation of a Rad51 recombinase filament that forms on single-stranded DNA (ssDNA) created at DSB ends. This filament facilitates the search for a homologous donor sequence and promotes strand invasion. Recently caffeine treatment has been shown to prevent gene targeting in mammalian cells by increasing non-productive Rad51 interactions between the DSB and random regions of the genome. Here we show that caffeine treatment prevents gene conversion in yeast, independently of its inhibition of the Mec1ATR/Tel1ATM-dependent DNA damage response or caffeine's inhibition of 5′ to 3′ resection of DSB ends. Caffeine treatment results in a dosage-dependent eviction of Rad51 from ssDNA. Gene conversion is impaired even at low concentrations of caffeine, where there is no discernible dismantling of the Rad51 filament. Loss of the Rad51 filament integrity is independent of Srs2's Rad51 filament dismantling activity or Rad51's ATPase activity and does not depend on non-specific Rad51 binding to undamaged double-stranded DNA. Caffeine treatment had similar effects on irradiated HeLa cells, promoting loss of previously assembled Rad51 foci. We conclude that caffeine treatment can disrupt gene conversion by disrupting Rad51 filaments. PMID:26019181

School-based early childhood education and age-28 well-being: effects by timing, dosage, and subgroups.

Science.gov (United States)

Reynolds, Arthur J; Temple, Judy A; Ou, Suh-Ruu; Arteaga, Irma A; White, Barry A B

2011-07-15

Advances in understanding the effects of early education have benefited public policy and developmental science. Although preschool has demonstrated positive effects on life-course outcomes, limitations in knowledge on program scale, subgroup differences, and dosage levels have hindered understanding. We report the effects of the Child-Parent Center Education Program on indicators of well-being up to 25 years later for more than 1400 participants. This established, publicly funded intervention begins in preschool and provides up to 6 years of service in inner-city Chicago schools. Relative to the comparison group receiving the usual services, program participation was independently linked to higher educational attainment, income, socioeconomic status (SES), and health insurance coverage, as well as lower rates of justice-system involvement and substance abuse. Evidence of enduring effects was strongest for preschool, especially for males and children of high school dropouts. The positive influence of four or more years of service was limited primarily to education and SES. Dosage within program components was mostly unrelated to outcomes. Findings demonstrate support for the enduring effects of sustained school-based early education to the end of the third decade of life.

Geometry of modified release formulations during dissolution--influence on performance of dosage forms with diclofenac sodium.

Science.gov (United States)

Dorożyński, Przemysław; Kulinowski, Piotr; Jamróz, Witold; Juszczyk, Ewelina

2014-12-30

The objectives of the work included: presentation of magnetic resonance imaging (MRI) and fractal analysis based approach to comparison of dosage forms of different composition, structure, and assessment of the influence of the compositional factors i.e., matrix type, excipients etc., on properties and performance of the dosage form during drug dissolution. The work presents the first attempt to compare MRI data obtained for tablet formulations of different composition and characterized by distinct differences in hydration and drug dissolution mechanisms. The main difficulty, in such a case stems from differences in hydration behavior and tablet's geometry i.e., swelling, cracking, capping etc. A novel approach to characterization of matrix systems i.e., quantification of changes of geometrical complexity of the matrix shape during drug dissolution has been developed. Using three chosen commercial modified release tablet formulations with diclofenac sodium we present the method of parameterization of their geometrical complexity on the base of fractal analysis. The main result of the study is the correlation between the hydrating tablet behavior and drug dissolution - the increase of geometrical complexity expressed as fractal dimension relates to the increased variability of drug dissolution results. Copyright © 2014 Elsevier B.V. All rights reserved.

Measurement of in-vivo dosage increase due to dental alloys during therapeutic irradiation of the mouth cavity

International Nuclear Information System (INIS)

Thilmann, C.; Mose, S.; Saran, F.; Schopohl, B.; Boettcher, H.D.

1995-01-01

The degree of dosage increase in the immediate surrounding of metallic dental materials was measured in an in-vivo study during therapeutic irradiation with 60 Co gamma rays in the area of mouth cavity of 11 patients. Measurements were carried out by thermoluminescent dosimetry at permamently fixed golden teeth and alloy specimens containing gold and palladium and amalgam. The following relative dodage values according to a simultanelusly measured reference value were measured at the surface of the different dental materials: 161% near fixed golden caps, 168% near the specimen containing gold in a high percentage, 133% near the specimen of palladium and 161% near the specimen of amalgam. The in vivo measured dosage increases due to metallic dental prosthesis are less than values obtained using back scatter arramgements for irradiating phantoms. Despite this, they could be of clinical relevance. Thus the usage of a mucous membrane protection during irradiation with 60 Co, as a means of preventing local lesions of the oral mucosa, due to dental alloys within the treatment volume remains inevitable. (orig.) [de

Innate Functions of Immunoglobulin M Lessen Liver Gene Transfer with Helper-Dependent Adenovirus

Science.gov (United States)

Unzu, Carmen; Morales-Kastresana, Aizea; Sampedro, Ana; Serrano-Mendioroz, Irantzu; Azpilikueta, Arantza; Ochoa, María Carmen; Dubrot, Juan; Martínez-Ansó, Eduardo

2014-01-01

The immune system poses obstacles to viral vectors, even in the first administration to preimmunized hosts. We have observed that the livers of B cell-deficient mice were more effectively transduced by a helper-dependent adenovirus serotype-5 (HDA) vector than those of WT mice. This effect was T-cell independent as shown in athymic mice. Passive transfer of the serum from adenovirus-naïve WT to Rag1KO mice resulted in a reduction in gene transfer that was traced to IgM purified from serum of adenovirus-naïve mice. To ascribe the gene transfer inhibition activity to either adenoviral antigen-specific or antigen-unspecific functions of IgM, we used a monoclonal IgM antibody of unrelated specificity. Both the polyclonal and the irrelevant monoclonal IgM inhibited gene transfer by the HDA vector to either cultured hepatocellular carcinoma cells or to the liver of mice in vivo. Adsorption of polyclonal or monoclonal IgMs to viral capsids was revealed by ELISAs on adenovirus-coated plates. These observations indicate the existence of an inborn IgM mechanism deployed against a prevalent virus to reduce early post-infection viremia. In conclusion, innate IgM binding to adenovirus serotype-5 capsids restrains gene-transfer and offers a mechanism to be targeted for optimization of vector dosage in gene therapy with HDA vectors. PMID:24465560

Innate functions of immunoglobulin M lessen liver gene transfer with helper-dependent adenovirus.

Directory of Open Access Journals (Sweden)

Carmen Unzu

Full Text Available The immune system poses obstacles to viral vectors, even in the first administration to preimmunized hosts. We have observed that the livers of B cell-deficient mice were more effectively transduced by a helper-dependent adenovirus serotype-5 (HDA vector than those of WT mice. This effect was T-cell independent as shown in athymic mice. Passive transfer of the serum from adenovirus-naïve WT to Rag1KO mice resulted in a reduction in gene transfer that was traced to IgM purified from serum of adenovirus-naïve mice. To ascribe the gene transfer inhibition activity to either adenoviral antigen-specific or antigen-unspecific functions of IgM, we used a monoclonal IgM antibody of unrelated specificity. Both the polyclonal and the irrelevant monoclonal IgM inhibited gene transfer by the HDA vector to either cultured hepatocellular carcinoma cells or to the liver of mice in vivo. Adsorption of polyclonal or monoclonal IgMs to viral capsids was revealed by ELISAs on adenovirus-coated plates. These observations indicate the existence of an inborn IgM mechanism deployed against a prevalent virus to reduce early post-infection viremia. In conclusion, innate IgM binding to adenovirus serotype-5 capsids restrains gene-transfer and offers a mechanism to be targeted for optimization of vector dosage in gene therapy with HDA vectors.

Preparation and evaluation of doxycycline hydrochloride and bromhexine hydrochloride dosage forms for pigeons / Marga le Roux

OpenAIRE

Le Roux, Marga

2004-01-01

Objective: To prepare and evaluate three different dosage forms, containing doxycycline hydrochloride (HCI) and bromhexine hydrochloride (HCI) respectively and in combination, for the treatment of respiratory diseases in pigeons. Background: Birds have held a place in man's affection since the ancient Egyptians and Romans kept birds. Europeans have successfully bred birds, especially smaller birds and pigeons, for centuries. Only in recent years, however, have science and me...

Stability Indicating LC-Method for Estimation of Paracetamol and Lornoxicam in Combined Dosage Form

OpenAIRE

Shah, Dimal A.; Patel, Neel J.; Baldania, Sunil L.; Chhalotiya, Usman K.; Bhatt, Kashyap K.

2011-01-01

A simple, specific and stability indicating reversed phase high performance liquid chromatographic method was developed for the simultaneous determination of paracetamol and lornoxicam in tablet dosage form. A Brownlee C-18, 5 μm column having 250×4.6 mm i.d. in isocratic mode, with mobile phase containing 0.05 M potassium dihydrogen phosphate:methanol (40:60, v/v) was used. The flow rate was 1.0 ml/min and effluents were monitored at 266 nm. The retention times of paracetamol and lornoxicam ...

Application of wireless sensor networks in personnel dosage monitoring system of nuclear power plant

International Nuclear Information System (INIS)

Chen Yonghong; Zhang Dafa; Jiang Wei; Chen Dengke

2007-01-01

Aim to meet the need of personnel dosage monitoring of nuclear power plant, a monitoring system was designed which based on wireless sensor network. First, the basic concept was described; the characteristics of the wireless sensor network applied in the monitoring system of nuclear power plant were also been analyzed; the structure of the system was built too. Finally, the special technologies like the choice of communication mode, the security of communication network and orientation that used in the monitoring system were discussed. (authors)

Pharmacokinetics and Adverse Effects of 3 Sustained-release Buprenorphine Dosages in Healthy Guinea Pigs (Cavia porcellus).

Science.gov (United States)

Zanetti, Andrea S; Putta, Sumanth K; Casebolt, Donald B; Louie, Stan G

2017-11-01

In guinea pigs, studies addressing the efficacy, safety, and pharmacokinetic profiles of different sustained-release buprenorphine (SRB) formulations are still in their infancy. Here we assessed the pharmacokinetic profiles of 3 SRB dosages (SR-LAB, ZooPharm; SRBLow, 0.15 mg/kg; SRBMedium, 0.3 mg/kg; and SRBHigh, 0.6 mg/kg) for 72 h after a single subcutaneous administration to 8 (4 male and 4 female) healthy guinea pigs. Body weight, fecal output, and cortisol levels were also monitored and the results compared with those of the sham group. Within the first h after administration, the maximal plasma concentration (Cmax) of the drug was 64.3 ± 9.2 ng/mL (males) and 71.3 ± 3.7 ng/mL (females) in the SRBHigh group; 11.5 ± 3.2 ng/mL (males) and 6.9 ± 0.9 ng/mL (females) in the SRBMedium group; and 2.3 ± 0.8 ng/mL (males) and 2.0 ± 0.5 ng/mL (females) in the SRBLow group. After 72 h, therapeutic levels of the drug (>1 ng/mL) were observed only in guinea pigs treated with SRBHigh (both sexes) and males treated with SRBMediu cm. Fecal output (quantity and distribution) and body weight were significantly lower in the SRB groups as compared with the sham group, and with the SRBHigh group showing larger reductions. Baseline levels of serum cortisol in healthy females (1440 ± 106 ng/mL) were significantly greater than in males (550 ± 66 ng/mL). But, independent of the sex, SRB administration significantly reduced those levels. In conclusion, the data indicate that all 3 SRB dosages can be safely used in guinea pigs. However, therapeutic levels of the drug were observed for at least 48 h only guinea pigs treated with SRBHigh and SRBMedium. Further investigation is needed to determine if these dosages can alleviate pain in guinea pigs.

A systematic review of the use of dosage form manipulation to obtain required doses to inform use of manipulation in paediatric practice.

Science.gov (United States)

Richey, Roberta H; Hughes, Clare; Craig, Jean V; Shah, Utpal U; Ford, James L; Barker, Catrin E; Peak, Matthew; Nunn, Anthony J; Turner, Mark A

2017-02-25

This study sought to determine whether there is an evidence base for drug manipulation to obtain the required dose, a common feature of paediatric clinical practice. A systematic review of the data sources, PubMed, EMBASE, CINAHL, IPA and the Cochrane database of systematic reviews, was used. Studies that considered the dose accuracy of manipulated medicines of any dosage form, evidence of safety or harm, bioavailability, patient experience, tolerability, contamination and comparison of methods of manipulation were included. Case studies and letters were excluded. Fifty studies were eligible for inclusion, 49 of which involved tablets being cut, split, crushed or dispersed. The remaining one study involved the manipulation of suppositories of one drug. No eligible studies concerning manipulation of oral capsules or liquids, rectal enemas, nebuliser solutions, injections or transdermal patches were identified. Twenty four of the tablet studies considered dose accuracy using weight and/or drug content. In studies that considered weight using adapted pharmacopoeial specifications, the percentage of halved tablets meeting these specifications ranged from 30% to 100%. Eighteen studies investigated bioavailability, pharmacokinetics or clinical outcomes following manipulations which included nine delayed or modified release formulations. In each of these nine studies the entirety of the dosage form was administered. Only one of the 18 studies was identified where drugs were manipulated to obtain a proportion of the dosage form, and that proportion administered. The five studies that considered patient perception found that having to manipulate the tablets did not have a negative impact on adherence. Of the 49 studies only two studies reported investigating children. This review yielded limited evidence to support manipulation of medicines for children. The results cannot be extrapolated between dosage forms, methods of manipulation or between different brands of the same

Effects of Microencapsulated Synbiotic Administration at Different Dosages against heavy co-infection of White Spot Disease (WSD and Vibrio harveyi in Pacific White Shrimp (Litopenaeus vannamei

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Yunarty Yunarty

2016-12-01

Full Text Available White spot disease (WSD is one of infectious disease in shrimp caused by white spot syndrome virus (WSSV. This study aimed to determine the dosage immunological effects and growth performances of microencapsulated synbiotic (Bacillus NP5 and mannan oligosaccharide at different dosages on Pacific white shrimp.  The microencapsulated synbiotic   was administered as feed supplementation  against the co-infection of   WSSV and Vibrio harveyi. Synbiotic was encapsulated by spray drying method, further feed supplemented to Pacific white shrimp for 30 days at a  dosages of 0.5% (A, 1% (B, 2% (C and control treatments, i.e. without any microencapsulated synbiotic administration as positive control (D and negative control (E. The challenge test was performed on day 30 after feeding supplementation, then the experimental shrimps were injected by WSSV intramuscularly   at the infective dosage of 104 copies.-ml-1. Afterwards,   24 hours after WSSV injection the shrimps were immersed in water contained cells suspension of V. harveyi  at the cells population dosage of 106 CFU-.ml-1. All synbiotic treatments showed better results with the values of Total Haemocyte Count (THC, Phenoloxidase (PO and Respiratory Burst (RB, were higher (P<0.05 compared to positive control. The specific growth rates (SGR of A, B and C showed higher than both controls of D and E. The feed conversion ratio (FCR value of synbiotic treatments were lower (P<0.05 than both controls. However, the administration of microencapsulated synbiotic have not been able to prevent heavy impact of WSSV and V. harveyi co-infection due to lower SR and mortality pattern which continued to increase.   Keywords: Synbiotic, Litopenaeus vannamei, WSSV, Vibrio harveyi, co-infection

General Requirements to the Preparation of Tinctures, Decoctions. Dosage of Phytopreparations

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I.B. Yershovа

2016-09-01

Full Text Available The article describes the advantages and disadvantages of using herbal medicine, general information for the collection of medicinal plants. According to the World Health Organization, the classification of herbal medicine is an integral part of traditional medicine. It refers to the variety of metabolic therapy. This treatment meets the requirements of pathogenetic therapy. Currently, more than 30 % of medicines on the pharmaceutical market have herbal origin. According to the World Health Organization, about 80 % of the world population use mainly traditional medicines of natural origin within the framework of primary health care system. Analysis of publications on phytotherapy revealed insufficient coverage of contraindications and side effects of certain plants. This was the basis for opening in our magazine this column, and we wanted to start with what would be the advantages and disadvantages of phytotherapy. Benefits of herbal medi­cine: biological proximity of the active substances of plants and active substances of the body, harmony therapy for the human body, the prolonged effect of herbal medicines after the completion of therapy, the opportunity to prepare a wide variety of different dosage forms, for both indoor and outdoor use, compatibility with many synthetic pharmaceuticals drugs, comprehensive multilateral action of plants, no side effects, simplicity and ease of preparation of herbal remedies at home, the availability for the majority of patients due to the low cost of the medicines. Limitations of herbal medicine: the complexity of the standardization of the treatment effect of herbal drugs, the complexity of establishing a dose, selectivity of diseases, in which typical herbal remedies are prescribed, the risk of poisoning, particularly in self-collection of medicinal plants. The article also provides methods for the preparation of various forms of herbal remedies, dosage for adults and children. With all the advantages of

The evolutionary history of the SAL1 gene family in eutherian mammals

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Callebaut Isabelle

2011-05-01

Full Text Available Abstract Background SAL1 (salivary lipocalin is a member of the OBP (Odorant Binding Protein family and is involved in chemical sexual communication in pig. SAL1 and its relatives may be involved in pheromone and olfactory receptor binding and in pre-mating behaviour. The evolutionary history and the selective pressures acting on SAL1 and its orthologous genes have not yet been exhaustively described. The aim of the present work was to study the evolution of these genes, to elucidate the role of selective pressures in their evolution and the consequences for their functions. Results Here, we present the evolutionary history of SAL1 gene and its orthologous genes in mammals. We found that (1 SAL1 and its related genes arose in eutherian mammals with lineage-specific duplications in rodents, horse and cow and are lost in human, mouse lemur, bushbaby and orangutan, (2 the evolution of duplicated genes of horse, rat, mouse and guinea pig is driven by concerted evolution with extensive gene conversion events in mouse and guinea pig and by positive selection mainly acting on paralogous genes in horse and guinea pig, (3 positive selection was detected for amino acids involved in pheromone binding and amino acids putatively involved in olfactory receptor binding, (4 positive selection was also found for lineage, indicating a species-specific strategy for amino acid selection. Conclusions This work provides new insights into the evolutionary history of SAL1 and its orthologs. On one hand, some genes are subject to concerted evolution and to an increase in dosage, suggesting the need for homogeneity of sequence and function in certain species. On the other hand, positive selection plays a role in the diversification of the functions of the family and in lineage, suggesting adaptive evolution, with possible consequences for speciation and for the reinforcement of prezygotic barriers.

An Allometric Analysis of Sex and Sex Chromosome Dosage Effects on Subcortical Anatomy in Humans

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Clasen, Liv; Giedd, Jay N.; Blumenthal, Jonathan; Lerch, Jason P.; Chakravarty, M. Mallar; Raznahan, Armin

2016-01-01

Structural neuroimaging of humans with typical and atypical sex-chromosome complements has established the marked influence of both Yand X-/Y-chromosome dosage on total brain volume (TBV) and identified potential cortical substrates for the psychiatric phenotypes associated with sex-chromosome aneuploidy (SCA). Here, in a cohort of 354 humans with varying karyotypes (XX, XY, XXX, XXY, XYY, XXYY, XXXXY), we investigate sex and SCA effects on subcortical size and shape; focusing on the striatum, pallidum and thalamus. We find large effect-size differences in the volume and shape of all three structures as a function of sex and SCA. We correct for TBV effects with a novel allometric method harnessing normative scaling rules for subcortical size and shape in humans, which we derive here for the first time. We show that all three subcortical volumes scale sublinearly with TBV among healthy humans, mirroring known relationships between subcortical volume and TBV among species. Traditional TBV correction methods assume linear scaling and can therefore invert or exaggerate sex and SCA effects on subcortical anatomy. Allometric analysis restricts sex-differences to: (1) greater pallidal volume (PV) in males, and (2) relative caudate head expansion and ventral striatum contraction in females. Allometric analysis of SCA reveals that supernumerary X- and Y-chromosomes both cause disproportionate reductions in PV, and coordinated deformations of striatopallidal shape. Our study provides a novel understanding of sex and sex-chromosome dosage effects on subcortical organization, using an allometric approach that can be generalized to other basic and clinical structural neuroimaging settings. SIGNIFICANCE STATEMENT Sex and sex-chromosome dosage (SCD) are known to modulate human brain size and cortical anatomy, but very little is known regarding their impact on subcortical structures that work with the cortex to subserve a range of behaviors in health and disease. Moreover

Therapeutic dosages of aspirin counteract the IL-6 induced pro-tumorigenic effects by slowing down the ribosome biogenesis rate.

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Brighenti, Elisa; Giannone, Ferdinando Antonino; Fornari, Francesca; Onofrillo, Carmine; Govoni, Marzia; Montanaro, Lorenzo; Treré, Davide; Derenzini, Massimo

2016-09-27

Chronic inflammation is a risk factor for the onset of cancer and the regular use of aspirin reduces the risk of cancer development. Here we showed that therapeutic dosages of aspirin counteract the pro-tumorigenic effects of the inflammatory cytokine interleukin(IL)-6 in cancer and non-cancer cell lines, and in mouse liver in vivo. We found that therapeutic dosages of aspirin prevented IL-6 from inducing the down-regulation of p53 expression and the acquisition of the epithelial mesenchymal transition (EMT) phenotypic changes in the cell lines. This was the result of a reduction in c-Myc mRNA transcription which was responsible for a down-regulation of the ribosomal protein S6 expression which, in turn, slowed down the rRNA maturation process, thus reducing the ribosome biogenesis rate. The perturbation of ribosome biogenesis hindered the Mdm2-mediated proteasomal degradation of p53, throughout the ribosomal protein-Mdm2-p53 pathway. P53 stabilization hindered the IL-6 induction of the EMT changes. The same effects were observed in livers from mice stimulated with IL-6 and treated with aspirin. It is worth noting that aspirin down-regulated ribosome biogenesis, stabilized p53 and up-regulated E-cadherin expression in unstimulated control cells also. In conclusion, these data showed that therapeutic dosages of aspirin increase the p53-mediated tumor-suppressor activity of the cells thus being in this way able to reduce the risk of cancer onset, either or not linked to chronic inflammatory processes.

Therapeutic dosages of aspirin counteract the IL-6 induced pro-tumorigenic effects by slowing down the ribosome biogenesis rate

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Brighenti, Elisa; Giannone, Ferdinando Antonino; Fornari, Francesca; Onofrillo, Carmine; Govoni, Marzia; Montanaro, Lorenzo; Treré, Davide; Derenzini, Massimo

2016-01-01

Chronic inflammation is a risk factor for the onset of cancer and the regular use of aspirin reduces the risk of cancer development. Here we showed that therapeutic dosages of aspirin counteract the pro-tumorigenic effects of the inflammatory cytokine interleukin(IL)-6 in cancer and non-cancer cell lines, and in mouse liver in vivo. We found that therapeutic dosages of aspirin prevented IL-6 from inducing the down-regulation of p53 expression and the acquisition of the epithelial mesenchymal transition (EMT) phenotypic changes in the cell lines. This was the result of a reduction in c-Myc mRNA transcription which was responsible for a down-regulation of the ribosomal protein S6 expression which, in turn, slowed down the rRNA maturation process, thus reducing the ribosome biogenesis rate. The perturbation of ribosome biogenesis hindered the Mdm2-mediated proteasomal degradation of p53, throughout the ribosomal protein-Mdm2-p53 pathway. P53 stabilization hindered the IL-6 induction of the EMT changes. The same effects were observed in livers from mice stimulated with IL-6 and treated with aspirin. It is worth noting that aspirin down-regulated ribosome biogenesis, stabilized p53 and up-regulated E-cadherin expression in unstimulated control cells also. In conclusion, these data showed that therapeutic dosages of aspirin increase the p53-mediated tumor-suppressor activity of the cells thus being in this way able to reduce the risk of cancer onset, either or not linked to chronic inflammatory processes. PMID:27557515

Should we adjust erythropoiesis-stimulating agent dosage to postdialysis hemoglobin levels? A pilot study

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Castillo Nieves

2012-07-01

Full Text Available Abstract Background Predialysis hemoglobin (Hb may overestimate the true erithropoiesis-stimulating agents (ESA requeriments. We tested whether predialysis Hb is a reliable predictor of the postdialysis level to better control ESA dosage, and evaluated the relation between ESA, Hb and cardiovascular events (CVE. Methods Cohort study including 67 stable hemodialysis patients. Pre- and post-dialysis Hb concentrations were measured, and ESA doses were calculated. A model to predict post-dialysis Hb is proposed. During 18 months follow-up, CVE, hospitalizations and mortality were collected. Results After dialysis, Hb cocentration rise by 6.1 ± 5.6%. Using postdialysis Hb, the weight-adjusted ESA dosage would be lower respect to the prescription using predialysis Hb: 104 ± 120 vs 128 ± 124 U/kg/week (P P = 0.001. The prediction model is: Postdialysis Hb (g/dL = 1.636 + 0.871 x predialysis Hb* (g/dL + 0.099 x UF rate** (mL/kg/h - 0.39 for women***. [R2 = 0.74; *P P = 0.001; ***P = 0.03. Conclusions Postdialysis Hb can be a better reflect of the real Hb level in hemodialysis patients. Using postdialysis Hb would avoid the use of inappropriately high ESA doses. The prediction of postdialysis Hb with an adjusted model would help us to identify those patients at risk for ESA overdosification.

Determination of natural thorium in urines; Dosage du thorium dans les urines

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Jeanmaire, L; Jammet, H [Commissariat a l' Energie Atomique, Saclay (France).Centre d' Etudes Nucleaires

1959-07-01

A procedure for the quantitative analysis of thorium in urine is described. After precipitation with ammonium hydroxide, dissolution of the precipitate, extraction at pH 4-4.2 with cupferron in chloroformic solution and mineralization, a colorimetric determination of thorium with thorin is performed. It is thus possible to detect about 2 {gamma} of thorium in the sample. (author) [French] Cet article decrit une technique de dosage du thorium dans l'urine. Apres precipitation par l'ammoniaque, remise en solution, extraction a pH 4-4,2 par le cupferron en solution chloroformique et mineralisation, le thorium est dose par colorimetrie avec le thorin. Cette methode permet de deceler environ 2 {gamma} de thorium dans l'echantillon. (auteur)

Optimal dosage and duration of pivmecillinam treatment for uncomplicated lower urinary tract infections: a systematic review and meta-analysis

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Mariona Pinart

2017-05-01

Conclusions: There is insufficient evidence to support the use of an optimal combination of dosage, frequency, and duration of PIV therapy for the treatment of uncomplicated lower UTI. Evidence is limited due to the high risk of bias, poor reporting, and heterogeneous study data.

protVirt: protein dosage simulation by spectrometry assisting Biochemistry practical class

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Gabriel Gerber Hornink

2016-07-01

Full Text Available The practical classes in the teaching of biochemistry could provide great contributions to the process of teaching and learning, and the understanding of these by students depend on, generally,  previous concepts about the experiment and procedures performed. It is presented in this paper the educational software protVirt, which could be used as a pedagogical innovation in the method of practical classes involving dosage of proteins, focusing on the development of skills for understanding the activities. The software was developed in Adobe Flash, with the possibility of online or offline use. Despite the possibilities of using protVirt in various modalities of education, highlights the use in online courses, in which students develop, commonly, the practical class without the teacher centers, accompanied by monitors and tutors.

Methadone dosage and its relationship to quality of life, satisfaction, psychopathology, cognitive performance and additional consumption of non-prescribed drugs.

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Pedrero-Pérez, Eduardo J; MethaQoL, Grupo

2016-06-14

The effectiveness of methadone maintenance treatment is beyond any doubt, but there remains some incertitude about the appropriate and effective dosage and the objectives that should be achieved by this therapy. Some authors maintain that only doses higher than 50-60 mg/day ought to be considered effective, since only these block all the opioid receptors. But others propose the use of doses adjusted to the needs of the patient, based on their recovery process. Quality of life, satisfaction with treatment, psychopathological symptoms, cognitive performance and additional intake of illegal and unprescribed drugs were evaluated in a representative sample of all patients treated with opioid agonists in the Addiction Institute of Madrid (N = 1898, n = 450) and the Junta de Extremadura (N = 100, n = 65). The results revealed a negative relationship between dose and quality of life, psychopathological symptoms and cognitive performance. Satisfaction with treatment, based on doses negotiated together by doctor and patient, was very high, regardless of the dose. To establish hypothetical causal dependencies among the studied variables structural equation modelling was performed. The results reject the need for high dosage if not required by the patient, and highlight the benefits of other psychosocial interventions that lead to recovery, despite the chronification that could imply the use of high doses. Whereas high dosage programmes provide better indicators of social control, the patient's quality of life must be one of the main indicators of a successful treatment, as in any other health problem.

Explaining the slow transition of child-appropriate dosage formulations from the global to national level in the context of Uganda

DEFF Research Database (Denmark)

Nsabagasani, Xavier; Hansen, Ebba; Mbonye, Anthony

2015-01-01

validation meeting where preliminary findings were shared with stakeholders. Policy analysis and policy transfer theories were used to guide a deductive analysis for manifest and latent content. RESULTS: According to stakeholders, the transition to the globally recommended child-appropriate dosage...... formulations has been slow in Uganda due to a number of factors. These factors include resource constraints at the global and national levels, lack of Ministry of Health (MOH) formal commitment to the adoption of the child-appropriate dosage formulations policy and a lack of consensus between those who...... formulations still remains to be implemented in Uganda and other low income countries. This has been due to lack of resources that hindered formal transfer of the policy from the global to the local level. To achieve this transfer there is a need for resource mobilisation at both the international and local...

TTT and PIKK Complex Genes Reverted to Single Copy Following Polyploidization and Retain Function Despite Massive Retrotransposition in Maize.

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Garcia, Nelson; Messing, Joachim

2017-01-01

The TEL2, TTI1, and TTI2 proteins are co-chaperones for heat shock protein 90 (HSP90) to regulate the protein folding and maturation of phosphatidylinositol 3-kinase-related kinases (PIKKs). Referred to as the TTT complex, the genes that encode them are highly conserved from man to maize. TTT complex and PIKK genes exist mostly as single copy genes in organisms where they have been characterized. Members of this interacting protein network in maize were identified and synteny analyses were performed to study their evolution. Similar to other species, there is only one copy of each of these genes in maize which was due to a loss of the duplicated copy created by ancient allotetraploidy. Moreover, the retained copies of the TTT complex and the PIKK genes tolerated extensive retrotransposon insertion in their introns that resulted in increased gene lengths and gene body methylation, without apparent effect in normal gene expression and function. The results raise an interesting question on whether the reversion to single copy was due to selection against deleterious unbalanced gene duplications between members of the complex as predicted by the gene balance hypothesis, or due to neutral loss of extra copies. Uneven alteration of dosage either by adding extra copies or modulating gene expression of complex members is being proposed as a means to investigate whether the data supports the gene balance hypothesis or not.

TTT and PIKK Complex Genes Reverted to Single Copy Following Polyploidization and Retain Function Despite Massive Retrotransposition in Maize

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Nelson Garcia

2017-11-01

Full Text Available The TEL2, TTI1, and TTI2 proteins are co-chaperones for heat shock protein 90 (HSP90 to regulate the protein folding and maturation of phosphatidylinositol 3-kinase-related kinases (PIKKs. Referred to as the TTT complex, the genes that encode them are highly conserved from man to maize. TTT complex and PIKK genes exist mostly as single copy genes in organisms where they have been characterized. Members of this interacting protein network in maize were identified and synteny analyses were performed to study their evolution. Similar to other species, there is only one copy of each of these genes in maize which was due to a loss of the duplicated copy created by ancient allotetraploidy. Moreover, the retained copies of the TTT complex and the PIKK genes tolerated extensive retrotransposon insertion in their introns that resulted in increased gene lengths and gene body methylation, without apparent effect in normal gene expression and function. The results raise an interesting question on whether the reversion to single copy was due to selection against deleterious unbalanced gene duplications between members of the complex as predicted by the gene balance hypothesis, or due to neutral loss of extra copies. Uneven alteration of dosage either by adding extra copies or modulating gene expression of complex members is being proposed as a means to investigate whether the data supports the gene balance hypothesis or not.

Analytical Method Development and Validation of Solifenacin in Pharmaceutical Dosage Forms by RP-HPLC

OpenAIRE

Shaik, Rihana Parveen; Puttagunta, Srinivasa Babu; Kothapalli Bannoth, Chandrasekar; Challa, Bala Sekhara Reddy

2014-01-01

A new, accurate, precise, and robust HPLC method was developed and validated for the determination of solifenacin in tablet dosage form. The chromatographic separation was achieved on an Inertsil ODS 3V C18 (150 mm × 4.6 mm, 5 μm) stationary phase maintained at ambient temperature with a mobile phase combination of monobasic potassium phosphate (pH 3.5) containing 0.1% triethylamine and methanol (gradient mode) at a flow rate of 1.5 mL/min, and the detection was carried out by using UV detect...

ANALYTICAL STUDY OF CURCUMIN CONTENT IN DIFFERENT DOSAGE FORMS CONTAINING TURMERIC EXTRACT POWDER AND TURMERIC OLEORESIN

OpenAIRE

Rane Rajashree; Gangolli Divya; Patil Sushma; Ingawale Kanchan; Kundalwal Sachin

2013-01-01

Different dosage forms namely tablets, capsules, creams and syrups were analysed for curcumin content, by the well-known spectrophotometric method. Turmeric extract powder was used as a source of curcumin in capsule and tablet formulations. Turmeric oleoresin was used as a source of curcumin in cream formulation. Additionally, syrup formulations containing turmeric extract powder as well as turmeric oleoresin, separately, were also tested for their curcumin contents. Analytical results for cu...

Design and evaluation of buccal films as paediatric dosage form for transmucosal delivery of ondansetron.

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Trastullo, Ramona; Abruzzo, Angela; Saladini, Bruno; Gallucci, Maria Caterina; Cerchiara, Teresa; Luppi, Barbara; Bigucci, Federica

2016-08-01

In the process of implementation and innovation of paediatric dosage forms, buccal films for transmucosal administration of drug represent one of the most interesting approach. In fact, films are able to provide an extended duration of activity allowing minimal dosage and frequency and offer an exact and flexible dose, associated with ease of handling. The objective of the present study was to develop polymeric films for the sustained release of ondansetron hydrochloride, a selective inhibitor of 5-HT3 receptors indicated in paediatrics for the prevention and treatment of nausea and vomiting caused by cytotoxic chemotherapy or radiotherapy and postoperatively. Films were prepared by casting and drying of aqueous solutions containing different weight ratios of hydroxypropylmethylcellulose (HPMC) with chitosan (CH) or sodium hyaluronate (HA) or gelatin (GEL) and characterized for their physico-chemical and functional properties. The presence of HA, GEL and CH did not improve the mucoadhesive properties of HPMC film. The inclusion of GEL and CH in HPMC film increased in vitro drug release with respect to the inclusion of HA, although films containing HA showed the highest water uptake. Moreover in agreement with the release behaviour, the inclusion of CH and GEL provided higher drug permeation through porcine buccal mucosa with respect to HPMC film and ensured linear permeation profiles of drug. Copyright © 2016 Elsevier B.V. All rights reserved.

Encapsulated Synbiotic Dietary Supplementation at Different Dosages to Prevent Vibriosis in White Shrimp, Litopenaeus vannamei

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Anis Zubaidah

2015-10-01

Full Text Available The aim of this study was to evaluate the effect of encapsulated synbiotic (Bacillus sp. NP5 and oligosaccharide dietary at different dosages on growth performance, survival rate, feed conversion ratio, and immune responses of Litopenaeus vannamei against Vibrio infection. The shrimps of the main treatments were fed by the diet that contained three different dosages of encapsulated synbiotic [0.5% (A, 1% (B, and 2% (C (w/w] with feeding rate of 5% of shrimp biomass (4 times a day. The shrimps of two control treatments (negative control and positive control were fed only by commercial feed without supplementation of encapsulated synbiotic. The growth, feed conversion ratio, and survival rate were observed after 30 days of encapsulated synbiotic dietary. The shrimps were then challenged by injection of Vibrio harveyi (6 log colony forming units/mL 0.1 mL/shrimp, excluded the negative control treatment. Afterward, the survival and immune responses were observed for 9 days after experimental infection. The shrimps treated with 2% encapsulated synbiotic (treatment C in the diet showed the highest growth performance (2.98 ± 0.42%, feed conversion ratio (1.26 ± 0.19, and better immune responses i.e. total hemocyte counts, differential hemocyte count, phenoloxidase, and intestine bacteria observation compared to those of positive control treatment.

Altered GPM6A/M6 dosage impairs cognition and causes phenotypes responsive to cholesterol in human and Drosophila.

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Gregor, Anne; Kramer, Jamie M; van der Voet, Monique; Schanze, Ina; Uebe, Steffen; Donders, Rogier; Reis, André; Schenck, Annette; Zweier, Christiane

2014-12-01

Glycoprotein M6A (GPM6A) is a neuronal transmembrane protein of the PLP/DM20 (proteolipid protein) family that associates with cholesterol-rich lipid rafts and promotes filopodia formation. We identified a de novo duplication of the GPM6A gene in a patient with learning disability and behavioral anomalies. Expression analysis in blood lymphocytes showed increased GPM6A levels. An increase of patient-derived lymphoblastoid cells carrying membrane protrusions supports a functional effect of this duplication. To study the consequences of GPM6A dosage alterations in an intact nervous system, we employed Drosophila melanogaster as a model organism. We found that knockdown of Drosophila M6, the sole member of the PLP family in flies, in the wing, and whole organism causes malformation and lethality, respectively. These phenotypes as well as the protrusions of patient-derived lymphoblastoid cells with increased GPM6A levels can be alleviated by cholesterol supplementation. Notably, overexpression as well as loss of M6 in neurons specifically compromises long-term memory in the courtship conditioning paradigm. Our findings thus indicate a critical role of correct GPM6A/M6 levels for cognitive function and support a role of the GPM6A duplication for the patient's phenotype. Together with other recent findings, this study highlights compromised cholesterol homeostasis as a recurrent feature in cognitive phenotypes. © 2014 WILEY PERIODICALS, INC.

HPLC-DAD stability indicating determination of nizatidine in bulk and capsules dosage form

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Tarek S. Belal

2013-12-01

Full Text Available This work describes the stability-indicating determination of the H2-receptor antagonist nizatidine in its bulk and capsules dosage form using high performance liquid chromatography coupled with diode array detector (HPLC-DAD. The developed method involved the use of Thermo Hypersil BDS-C8 (4.6 × 250 mm, 5 μm particle size column and a mobile phase composed of 0.05 M phosphoric acid and acetonitrile (50:50, v/v. The mobile phase was pumped at a flow rate of 1 mL/min. Quantification of nizatidine was based on measuring its peak area at 320 nm. The retention time for nizatidine was about 3.61 min. The reliability and analytical performance of the proposed HPLC procedure were statistically validated with respect to linearity, range, precision, accuracy, specificity, robustness, detection and quantification limits. Calibration curve of nizatidine was linear in the range of 5–50 μg/mL with correlation coefficient >0.9999. The drug was subjected to forced-degradation conditions of acidic and basic hydrolysis, oxidation, dry heat and UV photolysis where it showed considerable degradation in basic and oxidative conditions. The proposed method proved to be specific and stability-indicating by resolution of the drug from its forced-degradation products. The validated HPLC method was applied to the analysis of nizatidine in capsules dosage form where it was quantified with recoveries not less than 98.2%. Assay results were statistically compared to USP 2011 pharmacopeial method where no significant difference was observed between the proposed and reference methods.

Resveratrol Exerts Dosage and Duration Dependent Effect on Human Mesenchymal Stem Cell Development

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Peltz, Lindsay; Gomez, Jessica; Marquez, Maribel; Alencastro, Frances; Atashpanjeh, Negar; Quang, Tara; Bach, Thuy; Zhao, Yuanxiang

2012-01-01

Studies in the past have illuminated the potential benefit of resveratrol as an anticancer (pro-apoptosis) and life-extending (pro-survival) compound. However, these two different effects were observed at different concentration ranges. Studies of resveratrol in a wide range of concentrations on the same cell type are lacking, which is necessary to comprehend its diverse and sometimes contradictory cellular effects. In this study, we examined the effects of resveratrol on cell self-renewal and differentiation of human mesenchymal stem cells (hMSCs), a type of adult stem cells that reside in a number of tissues, at concentrations ranging from 0.1 to 10 µM after both short- and long-term exposure. Our results reveal that at 0.1 µM, resveratrol promotes cell self-renewal by inhibiting cellular senescence, whereas at 5 µM or above, resveratrol inhibits cell self-renewal by increasing senescence rate, cell doubling time and S-phase cell cycle arrest. At 1 µM, its effect on cell self-renewal is minimal but after long-term exposure it exerts an inhibitory effect, accompanied with increased senescence rate. At all concentrations, resveratrol promotes osteogenic differentiation in a dosage dependent manner, which is offset by its inhibitory effect on cell self-renewal at high concentrations. On the contrary, resveratrol suppresses adipogenic differentiation during short-term exposure but promotes this process after long-term exposure. Our study implicates that resveratrol is the most beneficial to stem cell development at 0.1 µM and caution should be taken in applying resveratrol as an anticancer therapeutic agent or nutraceutical supplement due to its dosage dependent effect on hMSCs. PMID:22615926

Comparison of Dosage Requirement of Erythropoietin Stimulating Agent (ESA in Maintenance of Hemoglobin Concentration in patients undergoing twice weekly versus thrice weekly Hemodialysis in Pakistani Population

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Osama Kunwer Naveed

2018-03-01

Full Text Available Anemia is one of the major complications of patients with chronic kidney disease (CKD undergoing hemodialysis (HD and is associated with left ventricular hypertrophy and also increases morbidity and mortality. Anemia in patients with CKD can be due to two major reasons; iron deficiency or erythropoietin insufficiency. Erythropoietin Stimulating Agent (ESAs administration is the mainstay in treating anemia if the patient is iron sufficient. However, higher doses of ESAs have been associated with increased cerebrovascular and cardiovascular events. We conducted this study to see how much erythropoietin is required in our setting in iron sufficient patients to maintain hemoglobin(Hb  level and the effect of dialysis frequency on ESA doses.  Methods and Findings: A cross-sectional study was conducted at the Department of Nephrology at Ziauddin University Hospital. Patients’ charts were reviewed for Hb levels and doses of ESA to maintain Hb between 10-12 mg/dl. Patients were excluded if they had iron deficiency, malignancy, were on immunosuppressive agents, had renal transplant, and with Hb >12 mg/dl or <10 mg/dl and their ferritin levels, transferrin saturation, hemoglobin concentration, frequency of hemodialysis and ESA dosage were monitored. We also compared these variables between patients undergoing hemodialysis thrice weekly with those undergoing hemodialysis twice a week. A total of 105 patients were analyzed. 24 were excluded as they did not match the inclusion criteria. 81 patients were included in the study. 36 (44.4% were males and 45 (55.6% were females. Mean age of the patient was 56.47 ± 11.72 years. The average dose of ESA was 106.91 ± 61.47 for patients undergoing hemodialysis thrice weekly and 183.94 ± 116.71 for patients undergoing hemodialysis twice a week. Significant difference was found to exist between dosage of patients undergoing thrice weekly dialysis versus twice weekly dialysis(p=<0.001.  Our study has limitations

Nanofibrous solid dosage form of living bacteria prepared by electrospinning

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I. Wagner

2014-05-01

Full Text Available The aim of this work was to investigate the suitability of electrospinning for biodrug delivery and to develop an electrospinning-based method to produce vaginal drug delivery systems. Lactobacillus acidophilus bacteria were encapsulated into nanofibers of three different polymers (polyvinyl alcohol and polyvinylpyrrolidone with two different molar masses. Shelf life of the bacteria could be enhanced by the exclusion of water and by preparing a solid dosage form, which is an advantageous and patient-friendly way of administration. The formulations were stored at –20, 7 and 25°C, respectively. Viability testing showed that the nanofibers can provide long term stability for huge amounts of living bacteria if they are kept at (or below 7°C. Furthermore, all kinds of nanowebs prepared in this work dissolved instantly when they got in contact with water, thus the developed biohybrid nanowebs can provide new potential ways for curing bacterial vaginosis.

Effectiveness of different benfotiamine dosage regimens in the treatment of painful diabetic neuropathy.

Science.gov (United States)

Winkler, G; Pál, B; Nagybéganyi, E; Ory, I; Porochnavec, M; Kempler, P

1999-03-01

The therapeutic effectiveness of a benfotiamine (CAS 22457-89-2)-vitamin B combination (Milgamma-N), administered in high (4 x 2 capsules/day, = 320 mg benfotiamine/day) and medium doses (3 x 1 capsules/day), was compared to a monotherapy with benfotiamine (Benfogamma) (3 x 1 tablets/day, = 150 mg benfotiamine/day) in diabetic patients suffering from painful peripheral diabetic neuropathy (DNP). In a 6-week open clinical trial, 36 patients (aged 40 to 70 yrs) having acceptable metabolic control (HbA1c benfotiamine (p benfotiamine is most effective in large doses, although even in smaller daily dosages, either in combination or in monotherapy, it is effective.

Colorimetric determination of a paracetamole in raw material and in pharmaceutical dosage forms

International Nuclear Information System (INIS)

Usifoh, C.O; Adelusi, S.A.; Adebambo, R.F.

2002-01-01

A rapid, accurate and simple method is proposed for the determination of p-acetaminophen (paracetamole) in raw material, tablets and syrups. The method is based on measuring the intensity of the yellow color that developed when acute acetaminophen is allowed to react with p-dimethylaminobenzaldehyde in 2M HCl after heating. The color which absorbs in the visible region of gamma 450 nm is stable for several hours and the intensity is directly proportional to the concentration of the drug, that is, Beer lambert law is obeyed. The method can be used to analyse paracetamole in raw material and in pharmaceutical dosage forms. (author)

Hypomethylation and Aberrant Expression of the Glioma Pathogenesis-Related 1 Gene in Wilms Tumors

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Laxmi Chilukamarri

2007-11-01

Full Text Available Wilms tumors (WTs have a complex etiology, displaying genetic and epigenetic changes, including loss of imprinting (LOI and tumor suppressor gene silencing. To identify new regions of epigenetic perturbation in WTs, we screened kidney and tumor DNA using CpG island (CGI tags associated with cancer-specific DNA methylation changes. One such tag corresponded to a paralog of the glioma pathogenesis-related 1/related to testis-specific, vespid, and pathogenesis proteins 1 (GLIPR1/RTVP-1 gene, previously reported to be a tumor-suppressor gene silenced by hypermethylation in prostate cancer. Here we report methylation analysis of the GLIPR1/RTVP-1 gene in WTs and normal fetal and pediatric kidneys. Hypomethylation of the GLIPR1/RTVP-1 5'-region in WTs relative to normal tissue is observed in 21/24 (87.5% of WTs analyzed. Quantitative analysis of GLIPR1/RTVP-1 expression in 24 WTs showed elevated transcript levels in 16/24 WTs (67%, with 12 WTs displaying in excess of 20-fold overexpression relative to fetal kidney (FK control samples. Immunohistochemical analysis of FK and WT corroborates the RNA expression data and reveals high GLIPR1/RTVP-1 in WT blastemal cells together with variable levels in stromal and epithelial components. Hypomethylation is also evident in the WT precursor lesions and nephrogenic rests (NRs, supporting a role for GLIPR1/RTVP-1 deregulation early in Wilms tumorigenesis. Our data show that, in addition to gene dosage changes arising from LOI and hypermethylation-induced gene silencing, gene activation resulting from hypomethylation is also prevalent in WTs.

Unveiling multiple solid-state transitions in pharmaceutical solid dosage forms using multi-series hyperspectral imaging and different curve resolution approaches

DEFF Research Database (Denmark)

Alexandrino, Guilherme L; Amigo Rubio, Jose Manuel; Khorasani, Milad Rouhi

2017-01-01

Solid-state transitions at the surface of pharmaceutical solid dosage forms (SDF) were monitored using multi-series hyperspectral imaging (HSI) along with Multivariate Curve Resolution – Alternating Least Squares (MCR-ALS) and Parallel Factor Analysis (PARAFAC and PARAFAC2). First, the solid-stat...

Gene expression in a paleopolyploid: a transcriptome resource for the ciliate Paramecium tetraurelia

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Kapusta Aurélie

2010-10-01

Full Text Available Abstract Background The genome of Paramecium tetraurelia, a unicellular model that belongs to the ciliate phylum, has been shaped by at least 3 successive whole genome duplications (WGD. These dramatic events, which have also been documented in plants, animals and fungi, are resolved over evolutionary time by the loss of one duplicate for the majority of genes. Thanks to a low rate of large scale genome rearrangement in Paramecium, an unprecedented large number of gene duplicates of different ages have been identified, making this organism an outstanding model to investigate the evolutionary consequences of polyploidization. The most recent WGD, with 51% of pre-duplication genes still in 2 copies, provides a snapshot of a phase of rapid gene loss that is not accessible in more ancient polyploids such as yeast. Results We designed a custom oligonucleotide microarray platform for P. tetraurelia genome-wide expression profiling and used the platform to measure gene expression during 1 the sexual cycle of autogamy, 2 growth of new cilia in response to deciliation and 3 biogenesis of secretory granules after massive exocytosis. Genes that are differentially expressed during these time course experiments have expression patterns consistent with a very low rate of subfunctionalization (partition of ancestral functions between duplicated genes in particular since the most recent polyploidization event. Conclusions A public transcriptome resource is now available for Paramecium tetraurelia. The resource has been integrated into the ParameciumDB model organism database, providing searchable access to the data. The microarray platform, freely available through NimbleGen Systems, provides a robust, cost-effective approach for genome-wide expression profiling in P. tetraurelia. The expression data support previous studies showing that at short evolutionary times after a whole genome duplication, gene dosage balance constraints and not functional change are

Development and Validation of a HPLC Method for the Determination of Lacidipine in Pure Form and in Pharmaceutical Dosage Form

International Nuclear Information System (INIS)

Vinodh, M.; Vinayak, M.; Rahul, K.; Pankaj, P.

2012-01-01

A simple and reliable high-performance liquid chromatography (HPLC) method was developed and validated for Lacidipine in pure form and pharmaceutical dosage form. The method was developed on X bridge C-18 column (150 mm x 4.6 mm, 5 μm) with a mobile phase gradient system of ammonium acetate and acetonitrile. The effluent was monitored by PDA detector at 240 nm. Calibration curve was linear over the concentration range of 50-250 μg/ml. For Intra-day and inter-day precision % RSD values were found to be 0.83 % and 0.41 % respectively. Recovery of Lacidipine was found to be in the range of 99.78-101.76 %. The limits of detection (LOD) and quantification (LOQ) were 1.0 and 7.3 μg/ml respectively. The developed RP-HPLC method was successfully applied for the quantitative determination of lacidipine in pharmaceutical dosage. (author)

Predicting the oral pharmacokinetic profiles of multiple-unit (pellet) dosage forms using a modeling and simulation approach coupled with biorelevant dissolution testing: case example diclofenac sodium.

Science.gov (United States)

Kambayashi, Atsushi; Blume, Henning; Dressman, Jennifer B

2014-07-01

The objective of this research was to characterize the dissolution profile of a poorly soluble drug, diclofenac, from a commercially available multiple-unit enteric coated dosage form, Diclo-Puren® capsules, and to develop a predictive model for its oral pharmacokinetic profile. The paddle method was used to obtain the dissolution profiles of this dosage form in biorelevant media, with the exposure to simulated gastric conditions being varied in order to simulate the gastric emptying behavior of pellets. A modified Noyes-Whitney theory was subsequently fitted to the dissolution data. A physiologically-based pharmacokinetic (PBPK) model for multiple-unit dosage forms was designed using STELLA® software and coupled with the biorelevant dissolution profiles in order to simulate the plasma concentration profiles of diclofenac from Diclo-Puren® capsule in both the fasted and fed state in humans. Gastric emptying kinetics relevant to multiple-units pellets were incorporated into the PBPK model by setting up a virtual patient population to account for physiological variations in emptying kinetics. Using in vitro biorelevant dissolution coupled with in silico PBPK modeling and simulation it was possible to predict the plasma profile of this multiple-unit formulation of diclofenac after oral administration in both the fasted and fed state. This approach might be useful to predict variability in the plasma profiles for other drugs housed in multiple-unit dosage forms. Copyright © 2014 Elsevier B.V. All rights reserved.

Fine mapping and candidate gene analysis of the virescent gene v 1 in Upland cotton (Gossypium hirsutum).

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Mao, Guangzhi; Ma, Qiang; Wei, Hengling; Su, Junji; Wang, Hantao; Ma, Qifeng; Fan, Shuli; Song, Meizhen; Zhang, Xianlong; Yu, Shuxun

2018-02-01

The young leaves of virescent mutants are yellowish and gradually turn green as the plants reach maturity. Understanding the genetic basis of virescent mutants can aid research of the regulatory mechanisms underlying chloroplast development and chlorophyll biosynthesis, as well as contribute to the application of virescent traits in crop breeding. In this study, fine mapping was employed, and a recessive gene (v 1 ) from a virescent mutant of Upland cotton was narrowed to an 84.1-Kb region containing ten candidate genes. The GhChlI gene encodes the cotton Mg-chelatase I subunit (CHLI) and was identified as the candidate gene for the virescent mutation using gene annotation. BLAST analysis showed that the GhChlI gene has two copies, Gh_A10G0282 and Gh_D10G0283. Sequence analysis indicated that the coding region (CDS) of GhChlI is 1269 bp in length, with three predicted exons and one non-synonymous nucleotide mutation (G1082A) in the third exon of Gh_D10G0283, with an amino acid (AA) substitution of arginine (R) to lysine (K). GhChlI-silenced TM-1 plants exhibited a lower GhChlI expression level, a lower chlorophyll content, and the virescent phenotype. Analysis of upstream regulatory elements and expression levels of GhChlI showed that the expression quantity of GhChlI may be normal, and with the development of the true leaf, the increase in the Gh_A10G0282 dosage may partially make up for the deficiency of Gh_D10G0283 in the v 1 mutant. Phylogenetic analysis and sequence alignment revealed that the protein sequence encoded by the third exon of GhChlI is highly conserved across diverse plant species, in which AA substitutions among the completely conserved residues frequently result in changes in leaf color in various species. These results suggest that the mutation (G1082A) within the GhChlI gene may cause a functional defect of the GhCHLI subunit and thus the virescent phenotype in the v 1 mutant. The GhChlI mutation not only provides a tool for understanding the

Testing Transgenic Aspen Plants with bar Gene for Herbicide Resistance under Semi-natural Conditions.

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Lebedev, V G; Faskhiev, V N; Kovalenko, N P; Shestibratov, K A; Miroshnikov, A I

2016-01-01

Obtaining herbicide resistant plants is an important task in the genetic engineering of forest trees. Transgenic European aspen plants (Populus tremula L.) expressing the bar gene for phosphinothricin resistance have been produced using Agrobacterium tumefaciens-mediated transformation. Successful genetic transformation was confirmed by PCR analysis for thirteen lines derived from two elite genotypes. In 2014-2015, six lines were evaluated for resistance to herbicide treatment under semi-natural conditions. All selected transgenic lines were resistant to the herbicide Basta at doses equivalent to 10 l/ha (twofold normal field dosage) whereas the control plants died at 2.5 l/ha. Foliar NH4-N concentrations in transgenic plants did not change after treatment. Extremely low temperatures in the third ten-day period of October 2014 revealed differences in freeze tolerance between the lines obtained from Pt of f2 aspen genotypes. Stable expression of the bar gene after overwintering outdoors was confirmed by RT-PCR. On the basis of the tests, four transgenic aspen lines were selected. The bar gene could be used for retransformation of transgenic forest trees expressing valuable traits, such as increased productivity.

Standard PK/PD concepts can be applied to determine a dosage regimen for a macrolide: the case of tulathromycin in the calf.

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Toutain, P-L; Potter, T; Pelligand, L; Lacroix, M; Illambas, J; Lees, P

2017-01-01

The pharmacokinetic (PK) profile of tulathromycin, administered to calves subcutaneously at the dosage of 2.5 mg/kg, was established in serum, inflamed (exudate), and noninflamed (transudate) fluids in a tissue cage model. The PK profile of tulathromycin was also established in pneumonic calves. For Mannheimia haemolytica and Pasteurella multocida, tulathromycin minimum inhibitory concentrations (MIC) were approximately 50 times lower in calf serum than in Mueller-Hinton broth. The breakpoint value of the PK/pharmacodynamic (PD) index (AUC (0-24 h) /MIC) to achieve a bactericidal effect was estimated from in vitro time-kill studies to be approximately 24 h for M. haemolytica and P. multocida. A population model was developed from healthy and pneumonic calves and, using Monte Carlo simulations, PK/PD cutoffs required for the development of antimicrobial susceptibility testing (AST) were determined. The population distributions of tulathromycin doses were established by Monte Carlo computation (MCC). The computation predicted a target attainment rate (TAR) for a tulathromycin dosage of 2.5 mg/kg of 66% for M. haemolytica and 87% for P. multocida. The findings indicate that free tulathromycin concentrations in serum suffice to explain the efficacy of single-dose tulathromycin in clinical use, and that a dosage regimen can be computed for tulathromycin using classical PK/PD concepts. © 2016 John Wiley & Sons Ltd.

Screening computer-assisted dosage programs for anticoagulation with warfarin and other vitamin K antagonists: minimum safety requirements for individual programs

DEFF Research Database (Denmark)

Poller, L; Roberts, C; Ibrahim, S

2009-01-01

Based on the results of the previous European Action on Anticoagulation (EAA) multicenter study, a simplified minimum procedure is described for screening the safety and effectiveness of marketed programs for dosage of oral anticoagulant drugs (vitamin K antagonists). The aim was to demonstrate non...

Toward Higher QA: From Parametric Release of Sterile Parenteral Products to PAT for Other Pharmaceutical Dosage Forms.

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Hock, Sia Chong; Constance, Neo Xue Rui; Wah, Chan Lai

2012-01-01

Pharmaceutical products are generally subjected to end-product batch testing as a means of quality control. Due to the inherent limitations of conventional batch testing, this is not the most ideal approach for determining the pharmaceutical quality of the finished dosage form. In the case of terminally sterilized parenteral products, the limitations of conventional batch testing have been successfully addressed with the application of parametric release (the release of a product based on control of process parameters instead of batch sterility testing at the end of the manufacturing process). Consequently, there has been an increasing interest in applying parametric release to other pharmaceutical dosage forms, beyond terminally sterilized parenteral products. For parametric release to be possible, manufacturers must be capable of designing quality into the product, monitoring the manufacturing processes, and controlling the quality of intermediates and finished products in real-time. Process analytical technology (PAT) has been thought to be capable of contributing to these prerequisites. It is believed that the appropriate use of PAT tools can eventually lead to the possibility of real-time release of other pharmaceutical dosage forms, by-passing the need for end-product batch testing. Hence, this literature review attempts to present the basic principles of PAT, introduce the various PAT tools that are currently available, present their recent applications to pharmaceutical processing, and explain the potential benefits that PAT can bring to conventional ways of processing and quality assurance of pharmaceutical products. Last but not least, current regulations governing the use of PAT and the manufacturing challenges associated with PAT implementation are also discussed. Pharmaceutical products are generally subjected to end-product batch testing as a means of quality control. Due to the inherent limitations of conventional batch testing, this is not the most

Synthetic lethality between gene defects affecting a single non-essential molecular pathway with reversible steps.

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Andrei Zinovyev

2013-04-01

Full Text Available Systematic analysis of synthetic lethality (SL constitutes a critical tool for systems biology to decipher molecular pathways. The most accepted mechanistic explanation of SL is that the two genes function in parallel, mutually compensatory pathways, known as between-pathway SL. However, recent genome-wide analyses in yeast identified a significant number of within-pathway negative genetic interactions. The molecular mechanisms leading to within-pathway SL are not fully understood. Here, we propose a novel mechanism leading to within-pathway SL involving two genes functioning in a single non-essential pathway. This type of SL termed within-reversible-pathway SL involves reversible pathway steps, catalyzed by different enzymes in the forward and backward directions, and kinetic trapping of a potentially toxic intermediate. Experimental data with recombinational DNA repair genes validate the concept. Mathematical modeling recapitulates the possibility of kinetic trapping and revealed the potential contributions of synthetic, dosage-lethal interactions in such a genetic system as well as the possibility of within-pathway positive masking interactions. Analysis of yeast gene interaction and pathway data suggests broad applicability of this novel concept. These observations extend the canonical interpretation of synthetic-lethal or synthetic-sick interactions with direct implications to reconstruct molecular pathways and improve therapeutic approaches to diseases such as cancer.

Predictors of ovarian response in intrauterine insemination patients and development of a dosage nomogram

DEFF Research Database (Denmark)

Freiesleben, Nina La Cour; Lossl, K.; Bogstad, Jeanette Wulff

2008-01-01

, total Doppler score of the ovarian stromal blood flow, baseline FSH and oestradiol. Simple and multiple linear regressions were used for the statistical analysis. Appropriate ovarian response was defined as two to three mature follicles. Body weight (P = 0.001) and the number of antral follicles (P = 0.......004) were the strongest independent predictive factors of the number of mature follicles. In conclusion, body weight and antral follicle count may be used to achieve appropriate ovarian response for IUI in ovulatory patients. Based on this, a simple rFSH dosage nomogram was developed for individual ovarian...

Social cognitive role of schizophrenia candidate gene GABRB2.

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Shui Ying Tsang

Full Text Available The occurrence of positive selection in schizophrenia-associated GABRB2 suggests a broader impact of the gene product on population fitness. The present study considered the possibility of cognition-related GABRB2 involvement by examining the association of GABRB2 with psychosis and altruism, respectively representing psychiatric and psychological facets of social cognition. Four single nucleotide polymorphisms (SNPs were genotyped for quantitative trait analyses and population-based association studies. Psychosis was measured by either the Positive and Negative Syndrome Scale (PANSS or antipsychotics dosage, and altruism was based on a self-report altruism scale. The minor alleles of SNPs rs6556547, rs1816071 and rs187269 in GABRB2 were correlated with high PANSS score for positive symptoms in a Han Chinese schizophrenic cohort, whereas those of rs1816071 and rs1816072 were associated with high antipsychotics dosage in a US Caucasian schizophrenic cohort. Moreover, strongly significant GABRB2-disease associations were found among schizophrenics with severe psychosis based on high PANSS positive score, but no significant association was observed for schizophrenics with only mild psychosis. Interestingly, in addition to association with psychosis in schizophrenics, rs187269 was also associated with altruism in healthy Han Chinese. Furthermore, parallel to correlation with severe psychosis, its minor allele was correlated with high altruism scores. These findings revealed that GABRB2 is associated with psychosis, the core symptom and an endophenotype of schizophrenia. Importantly, the association was found across the breadth of the psychiatric (psychosis to psychological (altruism spectrum of social cognition suggesting GABRB2 involvement in human cognition.

Development and characterization of a gastroretentive dosage form composed of chitosan and hydroxyethyl cellulose for alendronate

OpenAIRE

Chen YC; Ho HO; Chiu CC; Sheu MT

2013-01-01

Ying-Chen Chen,1,* Hsiu-O Ho,1,* Chiao-Chi Chiu,1 Ming-Thau Sheu1,2 1School of Pharmacy, College of Pharmacy, Taipei Medical University, 2Clinical Research Center and Traditional Herbal Medicine Research Center, Taipei Medical University Hospital, Taipei, Taiwan*These authors contributed equally to this workAbstract: In this study, alendronate, the most commonly used biphosphonate for treating osteoporosis, was formulated as gastroretentive dosage form (GRDF) tablets to enhance its oral bioav...

Self-compacting concretes (SCC: comparison of methods of dosage

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B. F. Tutikian

Full Text Available The composition of a self-compacting concrete (SCC should be defined to fulfills a number of requirements, such as self-compactibility, strength and durability. This study aims to compare three methods of dosage for SCC with local materials, so as to determine which one is the most economical and rational, thus assisting the executor in making a decision and enabling economic and technical feasibility for its application. The methods used in the experimental program were: Nan Su et al., which was developed in 2001 [1]; Repette-Melo, which was proposed in 2005 [2]; and Tutikian & Dal Molin, which was developed in 2007 [3]. From the results obtained in the experimental program, it was observed that the method which presented the lowest cost and highest compressive strength at the ages of 7, 28 and 91 days was Tutikian & Dal Molin, while the one which reached the lowest chloride ion penetration, best compactness and highest elasticity modulus was Repette-Melo. In tests carried out in the fresh state, all tested methods yielded mixtures which comply with the self-compactibility levels required by ABNT NBR 15823:2010 [4].

Kinetic spectrophotometric method for the determination of perindopril erbumine in pure and commercial dosage forms

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Nafisur Rahman

2017-02-01

Full Text Available A kinetic spectrophotometric method has been developed for the determination of perindopril erbumine in pure and commercial dosage forms. The method is based on the reaction of drug with potassium permanganate in alkaline medium at room temperature (30 ± 1 °C. The reaction was followed spectrophotometrically by measuring the increase in absorbance with time at 603 nm and the initial rate, fixed time (at 8.0 min and equilibrium time (at 90.0 min methods were adopted for constructing the calibration graphs. All the calibration graphs are linear in the concentration range of 5.0–50.0 μg/ml. The limits of detection for initial rate, fixed time and equilibrium time methods were 0.752, 0.882 and 1.091 μg/ml, respectively. The activation parameters such as Ea, ΔH‡, ΔS‡ and ΔG‡ were also determined for the reaction and found to be 60.93 kJ/mol, 56.45 kJ/mol, 74.16 J/K mol and −6.53 kJ/mol, respectively. The variables were optimized and the proposed methods are validated as per ICH guidelines. The method has been further applied to the determination of perindopril erbumine in commercial dosage forms. The analytical results of the proposed methods when compared with those of the reference method show no significant difference in accuracy and precision and have acceptable bias.

The Case for DUF1220 Domain Dosage as a Primary Contributor to Anthropoid Brain Expansion

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Jonathon eKeeney

2014-06-01

Full Text Available Here we present the hypothesis that increasing copy number (dosage of sequences encoding DUF1220 protein domains is a major contributor to the evolutionary increase in brain size, neuron number and cognitive capacity that is associated with the primate order. We further propose that this relationship is restricted to the anthropoid sub-order of primates, with DUF1220 copy number markedly increasing in monkeys, further in apes, and most extremely in humans where the greatest number of copies (~272 haploid copies is found. We show that this increase closely parallels the increase in brain size and neuron number that has occurred among anthropoid primate species. We also provide evidence linking DUF1220 copy number to brain size within the human species, both in normal populations and in individuals associated with brain size pathologies (1q21-associated microcephaly and macrocephaly. While we believe these and other findings presented here strongly suggest increase in DUF1220 copy number is a key contributor to anthropoid brain expansion, the data currently available rely on correlative measures that, though considerable, do not yet provide direct evidence for a causal connection. Nevertheless, we believe the evidence presented is sufficient to provide the basis for a testable model which proposes that DUF1220 protein domain dosage increase is a main contributor to the increase in brain size and neuron number found among the anthropoid primate species and that is at its most extreme in human.

The Dosage Form of Aragh in Treatment, from the Iranian Traditional Medicine Perspective.

Science.gov (United States)

Adl, Mehdi; Emtiazi, Majid

2016-05-01

The Iranian traditional medicine is one of the branches of complementary medicine and it is based on using the dosage forms of plants. One of the most common forms of pharmaceutical plants is Aragh. Due to ease-of-use, distillate is a more acceptable form among the public. In this article, it is attempted to study the usage forms and effects of Aragh according to the valid traditional medicine resources. This article is a review of Iranian traditional medicine textbooks such as Makhzan-ul-dawiah, Gharabadin Kabir, Cannon of Medicine, and other recent texts on medical plants. According to the traditional medicine, the process of getting Aragh is a kind of distillation, which is performed by using Ghar and Alembic (the equipment that are used in distillation). Distillation is the process of extracting and refining the fluid of a plant. Aragh of the plants is much more effective on the body than the plant itself. Traditional medicine regards Aragh as a new kind of drug (medicine) that is rarely mentioned in older texts (except for golab). However, the modern medicine regards it as a dosage form of essence, which is dissolved in water. The more the essence, the better the distillate gets. According to the traditional medicine sources, since the time of Hakim Aghil Khorasani, Aragh was used more and more every day. About 100 kinds of Araghs are mentioned in ancient texts, which are extracted from simple plants. Considering the distillation process and the way it performs, and by knowing that Aragh is a plant's softest and the most influential entity, it seems that it has a huge effect on Arvah and Ghova, the main parts like heart and brain and nervous parts.

Radiation-induced progressive decreasing in the expression of reverse transcriptase gene of hEST2 and telomerase activity

International Nuclear Information System (INIS)

Zhu Hanneng; Chen Wenying; Xiong Sidong

2000-01-01

Telomerase is a ribonucleoprotein complex that adds heximeric repeats called telomeres to the growing ends of chromosomal DNA. Telomerase activity is present in a vast majority of tumors but is repressed in most normal tissues. Human telomerase catalytic subunit gene (hEST2) reverse transcriptase (RT) segment was cloned by PCR according to the sequence published in GeneBank. PCR was used to investigate the expression of the hEST2 RT segment in diverse tumors as well as in various normal tissues. Results indicated that hEST2 RT segment was detectable in tumor cells lines but not in normal cells and tissues. In order to identify the relationship between telomerase and the biological effect of radiation injury, HeLa cells, KB cells and A431 cells were employed to measure the change in telomerase activity after 60 Co-ray irradiation at RNA level and protein level. Quantitative PCR determined that expression of hEST2 RT segment that encodes seven motifs of the human telomeras decreased with increasing dosage of radiation. In addition, a PCR-based telomeric repeat amplification protocol was used to assay telomerase activity after exposure to radiation. The results strongly support the experiments we had made: Telomerase activity decreases with increasing dosage of radiation. We conclude that detection of the hEST2 RT segment by Northern blotting is a new method for detecting telomerase activity. Furthermore, radiation can cause a dose-dependent decrease in telomerase activity. The effect of radiation on telomerase is one possible reason for the death of cancer cells after irradiation. (author)

Designing and testing a chemical demulsifier dosage controller in a crude oil desalting plant: an artificial Intelligence-Based network approach

Energy Technology Data Exchange (ETDEWEB)

Alshehri, A.K.; Ricardez-Sandoval, L.A.; Elkamel, A. [Department of Chemical Engineering, University of Waterloo, Waterloo (Canada)

2010-06-15

The aim of this paper is to present an artificial neural network (ANN) controller trained on a historical data set that covers a wide operating range of the fundamental parameters that affect the demulsifier dosage in a crude oil desalting process. The designed controller was tested and implemented on-line in a gas-oil separation plant. The results indicate that the current control strategy overinjects chemical demulsifier into the desalting process whereas the proposed ANN controller predicts a lower demulsifier dosage while keeping the salt content within its specification targets. Since an on-line salt analyzer is not available in the desalting plant, an ANN based on historical measurements of the salt content in the desalting process was also developed. The results show that the predictions made by this ANN controller can be used as an on-line strategy to predict and control the salt concentration in the treated oil. (Abstract Copyright [2010], Wiley Periodicals, Inc.)

Functional analysis of lipid metabolism genes in wine yeasts during alcoholic fermentation at low temperature.

Science.gov (United States)

López-Malo, María; García-Ríos, Estéfani; Chiva, Rosana; Guillamon, José M

2014-10-29

Wine produced by low-temperature fermentation is mostly considered to have improved sensory qualities. However few commercial wine strains available on the market are well-adapted to ferment at low temperature (10 - 15°C). The lipid metabolism of Saccharomyces cerevisiae plays a central role in low temperature adaptation. One strategy to modify lipid composition is to alter transcriptional activity by deleting or overexpressing the key genes of lipid metabolism. In a previous study, we identified the genes of the phospholipid, sterol and sphingolipid pathways, which impacted on growth capacity at low temperature. In the present study, we aimed to determine the influence of these genes on fermentation performance and growth during low-temperature wine fermentations. We analyzed the phenotype during fermentation at the low and optimal temperature of the lipid mutant and overexpressing strains in the background of a derivative commercial wine strain. The increase in the gene dosage of some of these lipid genes, e.g., PSD1 , LCB3, DPL1 and OLE1, improved fermentation activity during low-temperature fermentations, thus confirming their positive role during wine yeast adaptation to cold. Genes whose overexpression improved fermentation activity at 12°C were overexpressed by chromosomal integration into commercial wine yeast QA23. Fermentations in synthetic and natural grape must were carried out by this new set of overexpressing strains. The strains overexpressing OLE1 and DPL1 were able to finish fermentation before commercial wine yeast QA23. Only the OLE1 gene overexpression produced a specific aroma profile in the wines produced with natural grape must.

Comparative Sex Chromosome Genomics in Snakes: Differentiation, Evolutionary Strata, and Lack of Global Dosage Compensation

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Zektser, Yulia; Mahajan, Shivani; Bachtrog, Doris

2013-01-01

Snakes exhibit genetic sex determination, with female heterogametic sex chromosomes (ZZ males, ZW females). Extensive cytogenetic work has suggested that the level of sex chromosome heteromorphism varies among species, with Boidae having entirely homomorphic sex chromosomes, Viperidae having completely heteromorphic sex chromosomes, and Colubridae showing partial differentiation. Here, we take a genomic approach to compare sex chromosome differentiation in these three snake families. We identify homomorphic sex chromosomes in boas (Boidae), but completely heteromorphic sex chromosomes in both garter snakes (Colubridae) and pygmy rattlesnake (Viperidae). Detection of W-linked gametologs enables us to establish the presence of evolutionary strata on garter and pygmy rattlesnake sex chromosomes where recombination was abolished at different time points. Sequence analysis shows that all strata are shared between pygmy rattlesnake and garter snake, i.e., recombination was abolished between the sex chromosomes before the two lineages diverged. The sex-biased transmission of the Z and its hemizygosity in females can impact patterns of molecular evolution, and we show that rates of evolution for Z-linked genes are increased relative to their pseudoautosomal homologs, both at synonymous and amino acid sites (even after controlling for mutational biases). This demonstrates that mutation rates are male-biased in snakes (male-driven evolution), but also supports faster-Z evolution due to differential selective effects on the Z. Finally, we perform a transcriptome analysis in boa and pygmy rattlesnake to establish baseline levels of sex-biased expression in homomorphic sex chromosomes, and show that heteromorphic ZW chromosomes in rattlesnakes lack chromosome-wide dosage compensation. Our study provides the first full scale overview of the evolution of snake sex chromosomes at the genomic level, thus greatly expanding our knowledge of reptilian and vertebrate sex chromosomes

The zebrafish progranulin gene family and antisense transcripts

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Baranowski David

2005-11-01

Full Text Available Abstract Background Progranulin is an epithelial tissue growth factor (also known as proepithelin, acrogranin and PC-cell-derived growth factor that has been implicated in development, wound healing and in the progression of many cancers. The single mammalian progranulin gene encodes a glycoprotein precursor consisting of seven and one half tandemly repeated non-identical copies of the cystine-rich granulin motif. A genome-wide duplication event hypothesized to have occurred at the base of the teleost radiation predicts that mammalian progranulin may be represented by two co-orthologues in zebrafish. Results The cDNAs encoding two zebrafish granulin precursors, progranulins-A and -B, were characterized and found to contain 10 and 9 copies of the granulin motif respectively. The cDNAs and genes encoding the two forms of granulin, progranulins-1 and -2, were also cloned and sequenced. Both latter peptides were found to be encoded by precursors with a simplified architecture consisting of one and one half copies of the granulin motif. A cDNA encoding a chimeric progranulin which likely arises through the mechanism of trans-splicing between grn1 and grn2 was also characterized. A non-coding RNA gene with antisense complementarity to both grn1 and grn2 was identified which may have functional implications with respect to gene dosage, as well as in restricting the formation of the chimeric form of progranulin. Chromosomal localization of the four progranulin (grn genes reveals syntenic conservation for grna only, suggesting that it is the true orthologue of mammalian grn. RT-PCR and whole-mount in situ hybridization analysis of zebrafish grns during development reveals that combined expression of grna and grnb, but not grn1 and grn2, recapitulate many of the expression patterns observed for the murine counterpart. This includes maternal deposition, widespread central nervous system distribution and specific localization within the epithelial

Design of ANFIS Structures and GMDH Type-Neural Network for Prediction of Optimum Coagulant Dosage in Water Treatment Process Case Study: Great Water Treatment Plant in Guilan Province

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Allahyar Daghbandan

2015-11-01

Full Text Available Given the increasing importance of surface water bodies as supply sources of drinking water and regarding the requirement for using different chemicals at various stages of water treatment processes, it is essential to investigate coagulant consumption in water treatment plants. Determination of the required dosage of coagulants used in the coagulation and flocculation unit is one of the most important decisions in water treatment operations. For this purpose, the jar test is generally used to determine the type and concentration of suitable coagulants in a water treatment plant. However, the test is rather time-consuming and unreliable due to the inaccurate results it yields. Instead, intelligent methods can be employed to overcome this shortcoming of the jar test. In this study, experimental data were collected over the period from 2011 to 2012 and further refined for study. Two non-linear models based on adaptive neuro-fuzzy inference system (ANFIS and GMDH-type neural networks were then developed and experimental results were used to determine the optimum poly-aluminium chloride dosage for use at Guilan water treatment plant. The effects of input parameters including temperature, pH, turbidity, suspended solids, electrical conductivity, and color were investigated on coagulant dosage. The ANFIS model was found to outperform the GMDH model in predicting the required poly-aluminium chloride dosage.

Development of polymer film dosage forms of lidocaine for buccal administration: II. Comparison of preparation methods.

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Okamoto, Hirokazu; Nakamori, Takahiko; Arakawa, Yotaro; Iida, Kotaro; Danjo, Kazumi

2002-11-01

In previous studies, we prepared film dosage forms of lidocaine (LC) with hydroxypropylcellulose (HPC) as a film base using the solvent evaporation (SE) method. However, from the viewpoint of environmental issues, a reduction in organic solvent use in pharmaceutical and other industries is required. In this study, we prepared the LC films by direct compression of the physical mixture (DCPM method) and direct compression of the spray dried powder (DCSD method). Magnesium stearate, which was required as a lubricant for direct compression, showed no effect on the LC release rate. The LC release rate (%/h) was independent of the compression pressure, but a higher pressure was preferable to easily remove the film from the punches. An increase in the film weight decreased the LC release rate expressed in %/h, whereas no significant effect of film weight was observed on the LC release rate from unit surface area expressed in mg/h/cm(2). The LC release rate (%/h) was independent of the LC content, suggesting that the LC release rate (mg/h) can be quantitatively controlled by changing the LC content in the formulation. The LC release rate and penetration rate were affected by the preparation method; that is, DCPM method dosage form. Copyright 2002 Wiley-Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 91:2424-2432, 2002

Simultaneous UV Spectrophotometric Determination of Cetrizine and Dextromethorphan in Tablet Dosage Form

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R. Vijayalakshmi

2010-01-01

Full Text Available Two accurate, precise, sensitve and economical procedures for simultaneous estimation of cetrizine and dextromethorphan in tablet dosage forms have been developed. First method employs formation and solving of simultaneous equations using 230 nm and 280 nm as two analytical wavelengths for both drugs in methanol. The second method is Q-analysis based on measurement of absorptivity at 224 nm (as isobestic point and 280 nm (λmax of CTZ. Cetrizine and dextromethorphan at their respective λmax 280 nm and 230 nm and at 224 nm (isobestic point shows linearity in a concentration range of 10-30 mcg/mL for both the drugs. The recovery studies confirmed accuracy of the proposed methods and low values of standard deviation confirmed precision of the methods. The methods were validated as per ICH guidelines.

New generation LDHI with an improved environmental profile[Low dosage hydrate inhibitors