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In Vitro Culture and Secondary Metabolite Isolation in BryophytesEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Bryophytes, the second largest group of land plants, are extremely rich in terpenoids, phenols, glycosides, and fatty acids. Although bryophytes could be used in medicine, their chemistry is not very well known and the problem remains to obtain enough quantity of same species for analysis. In vitro cultivation of bryophytes is the most appropriate way for large biomass production and isolate of numerous useful compounds showing some interesting biologic activities. This technique is also useful in developmental, cellular, molecular, biochemical, and eco-physiologic studies.
Source: Springer protocols feed by Pharmacology/Toxicology - March 31, 2009 Category: Drugs & Pharmacology Source Type: info

Micropropagation and In Vitro Conservation of Vanilla (Vanilla planifolia Andrews)Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Vanilla (Vanilla planifolia Andrews (syn. V. fragrans Salisb.), a source of natural vanillin, plays a major positive role in the economy of several countries. A native to the Central America, its primary gene pool is threatened by deforestation and over collection that has resulted in disappearance of natural habitats and wild species. Therefore, multiplication and conservation of vanilla diversity is of paramount importance because of its narrow genetic base. It plays an important role in the production of disease free planting material for commercial cultivation. Simple protocols for micropropagation, in vitro conservati...
Source: Springer protocols feed by Pharmacology/Toxicology - March 31, 2009 Category: Drugs & Pharmacology Source Type: info

Protocol for In Vitro Regeneration and Marker Glycoside Assessment in Swertia chirata Buch-HamEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
We have developed a rapid in vitro propagation system, via axillary shoot formation from nodal explants of Swertia chirata Buch Ham. Culture medium supplemented with 2 mg/L. BAP is best for direct shoot regeneration initially formed adventitious buds from axils of the nodal explants after 30 days. The reduced BAP concentration 0.5 mg/L proliferate shoots effectively. Kept the number of hyperhydrated shoots to minimal and induced on an average 22–38 shoots per flask (4.3 cm average length). The regenerated shoots (5- to 6-m long) formed roots very well in Murashige and Skoog (MS) medium devoid of any gr...
Source: Springer protocols feed by Pharmacology/Toxicology - March 31, 2009 Category: Drugs & Pharmacology Source Type: info

Protocols for Establishment of an In Vitro Collection of Medicinal Plants in the Genus ScutellariaEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The study of medicinal plants has many unique challenges and special considerations. These plants are studied for their specific chemistry, or pharmacologic activity. Plants are highly sensitive to their environment and respond through changes in their chemistry. To date, one of the biggest problems in the study of medicinal plants has been the acquisition of consistent, positively identified material for chemical analysis. Successful protocols for the collection, identification, and establishment of medicinal plants species in tissue culture is invaluable for future studies. This protocol outlines methods to establish Scu...
Source: Springer protocols feed by Pharmacology/Toxicology - March 31, 2009 Category: Drugs & Pharmacology Source Type: info

Protocols for In Vitro Culture and Phytochemical Analysis of Phyllanthus Species (Euphorbiaceae)Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
We developed reproducible protocols for micropropagation, callus culture, and root culture of the medicinal plant Phyllanthus urinaria, P. niruri, P. tenellus, P. corcovadensis, P. caroliniensis, P. stipulatus, and P. fraternus by using single node explants. Genotype-linked differences are visible among the Phyllanthus species concerning shoot culture, callus culture, and root culture growth. The protocols developed for phytochemical screening of callus and root extracts of P. urinaria, P. caroliniensis, P. stipulatus, and P. fraternus have shown the production of sterols and triterpenes. Both compounds are known to accoun...
Source: Springer protocols feed by Pharmacology/Toxicology - March 31, 2009 Category: Drugs & Pharmacology Source Type: info

In Vitro Clonal Propagation of Asparagus racemosus, a High Value Medicinal PlantEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Asparagus racemosus Willd., an important medicinal plant of tropical and subtropical India, is a potent phytoestrogen which is used extensively in the treatment of menopausal symptoms, diarrhea, dyspepsia, and neurodegenerative disorders. The multiple uses of this species have increased its commercial demand resulting in over-exploitation. Consequently, the plant is recognized as being “critically endangered” in its natural habitat. Development of an efficient micropropagation protocol will not only play a significant role in meeting the requirement of planting material for commercial cultivation, but also in a...
Source: Springer protocols feed by Pharmacology/Toxicology - March 31, 2009 Category: Drugs & Pharmacology Source Type: info

Micropropagation of Penthorum chinenseThrough Axillary BudsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Penthorum chinensePursh is a traditional medicinal herb in China. Micropropagation protocol of this plant has been established. The shoot induction rate is high by culturing nodal explants on Murashige and Skoog (MS) medium supplemented with 6-benzyladenine (BA) as compared with kinetin (Kn). After 6 wks, the highest shoot formation (5.2) is achieved in 59.2% nodal explants cultured on MS medium combined with 2.0 mg/L BA. After 4 wk of subculture on the fresh MS medium, the highest shoot multiplication rate 6.4 is accomplished. MS medium containing 1.0 mg/L BA is most suitable for shoot propagation. Individual well develop...
Source: Springer protocols feed by Pharmacology/Toxicology - March 31, 2009 Category: Drugs & Pharmacology Source Type: info

Establishment of Adventitious Root Cultures of Echinacea purpurea for the Production of Caffeic Acid DerivativesEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Echinacace purpurea (purple cone flower) is an important medicinal plant, and widely used for phytochemical purposes. The roots are traditionally used in herbal medicines and dietary supplements as an immunostimulant in treating inflammatory and viral diseases. Extensive research work has been carried out on both the induction of adventitious roots from E. purpurea as well as established small-scale (shake flask) to large-scale (bioreactor) cultures for the production of adventitious root biomass and caffeic acid derivatives. This chapter describes the methodologies of induction of adventitious roots from explants of E. pu...
Source: Springer protocols feed by Pharmacology/Toxicology - March 31, 2009 Category: Drugs & Pharmacology Source Type: info

In Vitro Propagation of Rauwolfia serpentina Using Liquid Medium, Assessment of Genetic Fidelity of Micropropagated Plants, and Simultaneous Quantitation of Reserpine, Ajmaline, and AjmalicineEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Rauwolfia serpentina holds an important position in the pharmaceutical world because of its immense anti-hypertensive properties resulting from the presence of reserpine in the oleoresin fraction of the roots. Poor seed viability, low seed germination rate, and enormous genetic variability are the major constraints for the commercial cultivation of R. serpentina through conventional mode. The present optimized protocol offers an impeccable end to end method from the establishment of aseptic cultures to in-vitro plantlet production employing semisolid as well liquid nutrient culture medium and assessment of their genetic fi...
Source: Springer protocols feed by Pharmacology/Toxicology - March 31, 2009 Category: Drugs & Pharmacology Source Type: info

Medicinal Properties, In Vitro Protocols and Secondary Metabolite Analyses of Scots PineEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Scots pine (Pinus sylvestris L.) is known as an economically important forest tree with a wide distribution throughout the Northern hemisphere. Recently, the species has also become recognized as a novel source of functional food and bioactive compounds with medicinal properties. The present paper provides up-to-date information on protocols for somatic embryogenesis (i.e., the most promising in vitro method for vegetative propagation of Scots pine). Endophyte protocols cover the topics of endophyte isolation, identification and elimination from in vitro cultures. Moreover, the protocols for secondary metabolite analyses a...
Source: Springer protocols feed by Pharmacology/Toxicology - March 31, 2009 Category: Drugs & Pharmacology Source Type: info

Saussurea medusa Cell Suspension Cultures for Flavonoid ProductionEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Saussurea medusa Maxim. is a valuable traditional Chinese herb. The flavonoids are the main active pharmaceutical compounds in this medicinal plant species and have effective anti-tumor and anti-inflammation properties. This species is now almost extinct in China because of over-exploitation. The establishment of plant cell cultures would be a promising alternative to avoid extinction of this species and establish cultivation for the production of bioactive flavonoids. The callus is induced from leaf explants of S. medusa on Murashiage and Skoog medium supplemented with 0.5 mg/L 6-BA, 2 mg/L NAA, 30 g/L sucrose, and 5 g/L ...
Source: Springer protocols feed by Pharmacology/Toxicology - March 31, 2009 Category: Drugs & Pharmacology Source Type: info

Large-scale In Vitro Multiplication of Crataeva nurvalaEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Conservation and propagation of species using biotechnologic tools—such as plant tissue culture—are relevant when natural propagation is hampered for various reasons. In vitro techniques allow mass multiplication and propagation under pathogen-free conditions but also override dependence on season for availability of plant material. Moreover, in vitro genetic manipulation of a species, invariably, requires a prestandardized tissue culture protocol for its multiplication.
Source: Springer protocols feed by Pharmacology/Toxicology - March 31, 2009 Category: Drugs & Pharmacology Source Type: info

Bilberry In Vitro Protocols and Analyses of Phenolic CompoundsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Bilberry or European blueberry (Vaccinium myrtillus L.) belongs to the most significant family of wild berries in Northern Europe and is recognized for its bioactive properties. Its fruits and leaves are rich with phenolic compounds, in particular flavonoids. Their health benefits have received notable attention in recent years. Bilberry is one of the richest sources of the anthocyanins, a subclass of flavonoids. The interest in bilberry cultivation is growing because of the high value of the fruit in global food markets. Tissue culture provides an efficient propagation method for the selected bilberry genotypes both for t...
Source: Springer protocols feed by Pharmacology/Toxicology - March 31, 2009 Category: Drugs & Pharmacology Source Type: info

In Vitro Propagation of Two Tuberous Medicinal Plants: Holostemma ada-kodien and Ipomoea mauritianaEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Medicinal plants are sources of important therapeutic aid for healing human diseases. The depletion of the wild resources has prompted conservation, propagation, and enhancement of resources for medicinal plants. Micropropagation offers an alternate method to propagate and improve medicinal plants through selection of high-yield lines and their efficient cloning. This chapter describes cost effective and efficient protocols that have been successfully applied for the micropropagation and large-scale production of quality planting material in two important tuberous medicinal plants viz., Holostemma ada-kodien Schult. ...
Source: Springer protocols feed by Pharmacology/Toxicology - March 31, 2009 Category: Drugs & Pharmacology Source Type: info

In Vitro Production of Gymnemic Acid from Gymnema sylvestre (Retz) R. Br. Ex Roemer and Schultes Through Callus Culture Under Abiotic Stress ConditionsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Plant secondary metabolites have enormous potential for research and new drug development. Many secondary metabolites have a complex and unique structure and their production is often enhanced by biotic and abiotic stress conditions. Gymnemic acid (C43H68O14), a pentacyclic triterpenoid isolated from the leaves of Gymnema sylvestre, exhibits potent inhibitory effect on diabetes. The gymnemic acid content is determined by chromatographic methods: Camag HPTLC system equipped with a sample applicator Linomat IV and TLC scanner and integration software CAT 4.0. In HPLC C18 (ODS) reverse phase column; water 486 UV detector; mob...
Source: Springer protocols feed by Pharmacology/Toxicology - March 31, 2009 Category: Drugs & Pharmacology Source Type: info

Establishment of Plant Regeneration and Cryopreservation System from Zygotic Embryo-Derived Embryogenic Cell Suspension Cultures of Ranunculus kazusensisEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
This chapter describes culture conditions for high-frequency plant regeneration via somatic embryogenesis and cryopreservation from cell suspension cultures of Ranunculus kazusensis. Zygotic embryos form white nodular structures and pale-yellow calli at a frequency of 84.9% on half-strength Schenk and Hildebrandt (SH) medium supplemented with 0.1 mg/L 2,4-dichlorophenoxyacetic acid (2,4- d). However, the frequency of white nodular structure and off-white callus formation decreases to 25% with an increasing concentration of 2,4- d up to 10 mg/L cell suspension cultures are established from zygotic embryo-derived pale-yellow...
Source: Springer protocols feed by Pharmacology/Toxicology - March 31, 2009 Category: Drugs & Pharmacology Source Type: info

Spontaneous Plant Regeneration and Production of Secondary Metabolites from Hairy Root Cultures of Centaurium erythraea RafnEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
We have established an efficient protocol for plant regeneration and production of secondary metabolites in hairy root culture of Centaurium erythraea Rafn. Because the hairy roots and regenerated plants produce bitter secoiridoid glucosides and xanthones similar to the plants in nature, the use of in vitro cultures as an alternative source of their production is feasible. This chapter describes a protocol for the induction of adventitious shoots and transgenic plants from hairy root cultures of C. erythraea and their phytochemical analysis.
Source: Springer protocols feed by Pharmacology/Toxicology - March 31, 2009 Category: Drugs & Pharmacology Source Type: info

Transgenic Hypericum perforatumEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Plant transformation is an important tool with many applications in modern plant biology. Although this technique is primarily used to produce superior crop varieties, it is also being utilized to answer basic questions concerning gene function and regulation in contemporary functional genomics research. In our laboratory, we have established a transformation system for Hypericum perforatum. This protocol involves the transfer of foreign DNA into H. perforatum organogenic nodule explants via particle-bombardment and the regeneration of shoots from the explants under selection pressure. We have successfully used this method...
Source: Springer protocols feed by Pharmacology/Toxicology - March 31, 2009 Category: Drugs & Pharmacology Source Type: info

Agrobacterium-Mediated Transformation of Ruta graveolens LEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Agrobacterium tumefaciens is used to develop a genetic transformation method for a medicinal plant Ruta graveolens. The direct plant regeneration strategy is preferred to callus line establishment. In vitro seedlings, 2- –to 3-wk-old, are used to excise hypocotyls and co-cultivated for 3 d with A. tumefaciens strain C58C1RifR containing plasmid pTDE4 harbouring neomycin phosphotransferase (npt II, kanamycin resistance) and β-glucuronidase encoding genes. The Southern blot analysis has shown that 78% kanamycin resistant plants contain gene encoding β-glucuronidase. The GUS histochemical assay shows that 67% ...
Source: Springer protocols feed by Pharmacology/Toxicology - March 31, 2009 Category: Drugs & Pharmacology Source Type: info

Gene Expression Profiling in Taxus baccata L. Seedlings and Cell CulturesEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Limited native resources of paclitaxel from Taxus trees initiated the research to produce this compound by biotechnology. In vitro plant cell culture systems have been used for large-scale production of paclitaxel and related taxanes. In the past decade, several genes involved in the taxane biosynthetic pathway have already been sequenced and cloned. This protocol details how to derive cell cultures of Taxus baccata L. from young stems of mature trees and from all parts of in vitro- grown seedlings such as root segments, hypocotyls, and cotyledons. The time-course of expression of two genes – dbat and dbtnbt – ...
Source: Springer protocols feed by Pharmacology/Toxicology - March 31, 2009 Category: Drugs & Pharmacology Source Type: info

Catapol Production in Chinese Foxglove (Rehmannia glutinosa Libos.) Hairy Roots Transformed with Agrobacterium rhizogenes ATCC15834Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Hairy root clones of Rehmannia glutinosa were established via transformation with Agrobacterium rhizogenes ATCC15834. To optimize the culturing conditions for both root growth and catalpol production, the effects of various combinations of seven basal media, pH, and carbon sources were examined in the dark. The fastest root growth was obtained in an SH medium containing 4% sucrose, pH 5.8. The highest catalpol content (0.54% dry weight) was achieved in a WPM medium supplemented with 4% sucrose, pH 5.8. Effects of plant growth regulators and chitosan were also investigated. Auxin 2 mg/L IAA significantly increased both root...
Source: Springer protocols feed by Pharmacology/Toxicology - March 31, 2009 Category: Drugs & Pharmacology Source Type: info

Identification of Medicinal Plants and Plant Sequences: Multiplexed MLPA AssayEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
We describe the method for the MLPA procedure in detail, including the microarray hybridization protocol.
Source: Springer protocols feed by Pharmacology/Toxicology - March 31, 2009 Category: Drugs & Pharmacology Source Type: info

Isolation of Microsatellites from Catharanthus roseus (L.) G. Don Using Enriched LibrariesEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Catharanthus roseus is an indispensable source of the anticancerous alkaloids-vincristine and vinblastine, even though they are produced in trace amounts in vivo. In order to increase the yield of alkaloids, in vitro tissue culture studies are carried out which result in a large number of lines/cultures. For identification and characterization of the in vitro cultures, microsatellites in the form of STMS (Sequenced Tagged Microsatellite Sites) markers are used for identification of genetic polymorphism. STMS markers are also used for assessment of genetic diversity within natural populations as well as for construction of ...
Source: Springer protocols feed by Pharmacology/Toxicology - March 31, 2009 Category: Drugs & Pharmacology Source Type: info

Production of Cinnamyl Glycosides in Compact Callus Aggregate Cultures of Rhodiola rosea Through Biotransformation of Cinnamyl AlcoholEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Rhodiola rosea is a multipurpose medicinal plant with adaptogenic properties: it increases the body’s nonspecific resistance and normalizes body functions. The commercial interest for roseroot-based products has quickly increased worldwide. Nearly all raw-materials originate from natural populations. As a result of the intensive collection the species has become endangered. Production of the pharmaceutical compounds from the medicinal plants in cell cultures is an alternative to field cultivation. The present protocol describes the establishment of compact callus aggregate culture of Rhodiola rosea and the production...
Source: Springer protocols feed by Pharmacology/Toxicology - March 31, 2009 Category: Drugs & Pharmacology Source Type: info

Spearmint Plantlet Culture System as a Means to Study Secondary MetabolismEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Spearmint has one major monoterpene, (−)-carvone, that constitutes up to 90% of all the monoterpenes present. Likewise, the major phenylpropanoid—rosmarinic acid—in spearmint accounts for up to 70% of the phenylpropanoids produced from the plant. These two compounds are each produced by separate distinct biosynthetic pathways which provide an excellent opportunity to study the influence of a wide number of environmental and chemical conditions on secondary metabolism and plant growth. The techniques presented in this chapter employ 1 g of fresh weight material for each secondary metabolite analyses. Analy...
Source: Springer protocols feed by Pharmacology/Toxicology - March 31, 2009 Category: Drugs & Pharmacology Source Type: info

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The field of toxicogenomics has been advancing during the past decade or so since its origin. Most pharmaceutical companies are using it in one or more ways to improve their productivity and supplement their classic toxicology studies. Acceptance of toxicogenomics will continue to grow as regulatory concerns are addressed, proof of concept studies are disseminated more fully, and internal case studies show value for the use of this new technology in concert with classic testing.
Source: Springer protocols feed by Pharmacology/Toxicology - October 1, 2008 Category: Drugs & Pharmacology Source Type: info

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There is a need for new biomarkers to enable faster detection of adverse events due to drugs and disease processes. One would prefer biomarkers that are useful in multiple species (i.e., translational or bridging biomarkers) so that it would be possible to directly link responses between species and follow such injury in both preclinical and clinical settings. This chapter will explore some of the issues surrounding the use of pharmacogenomics to identify and qualify such biomarkers, and examples will be provided.
Source: Springer protocols feed by Pharmacology/Toxicology - October 1, 2008 Category: Drugs & Pharmacology Source Type: info

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Public consortia provide a forum for addressing questions requiring more resources than one organization alone could bring to bear and engaging many sectors of the scientific community. They are particular well suited for tackling some of the questions encountered in the field of toxicogenomics, where the number of studies and microarray analyses would be prohibitively expensive for a single organization to carry out. Five consortia that stand out in the field of toxicogenomics are the Institutional Life Sciences Institute (ILSI) Health and Environmental Sciences Institute (HESI) Committee on the Application of Genomics to...
Source: Springer protocols feed by Pharmacology/Toxicology - October 1, 2008 Category: Drugs & Pharmacology Source Type: info

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Scientists in the pharmaceutical industry have ready access to samples from animal toxicology studies carefully designed to test the safety characteristics of a steady pipeline of agents advancing toward clinical testing. Applications of toxicogenomics to the evaluation of compounds could best be realized if this promising technology could be implemented in these studies fully anchored in the traditional study end points currently used to characterize phenotypic outcome and to support the safe conduct of clinical testing. Regulatory authorities worldwide have declared their support for toxicogenomics and related technologi...
Source: Springer protocols feed by Pharmacology/Toxicology - October 1, 2008 Category: Drugs & Pharmacology Source Type: info

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Microarray technologies can be used to generate massive amounts of gene expression information as an initial step to decipher the molecular mechanisms of toxicologic changes. Identifying genes whose expression is associated with specific toxic end points is an initial step in predicting, characterizing, and understanding toxicity. Analysis of gene function and the chronology of gene expression changes represent additional methods to generate hypotheses of the mechanisms of toxicity. Follow-up experiments are typically required to confirm or refute hypotheses derived from toxicogenomic data. Understanding the mechanism of t...
Source: Springer protocols feed by Pharmacology/Toxicology - October 1, 2008 Category: Drugs & Pharmacology Source Type: info

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The generation of high-quality microarray data for toxicogenomics can be affected by the study design and methods used for sample acquisition, preparation, and processing. Bias can be introduced during animal treatment, tissue handling, and sample preparation. Metrics and controls used in assessing RNA integrity and the quality of microarray sample generation are reviewed in this chapter. Regulations and guidelines involved in the application of microarrays as a commercial in vitro diagnostic device are also described.
Source: Springer protocols feed by Pharmacology/Toxicology - October 1, 2008 Category: Drugs & Pharmacology Source Type: info

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In this chapter, we provide a structured approach to the statistical analysis of toxicogenomic data, from the assessment of data quality to data exploration, gene and pathway level analysis, and finally predictive model building. This type of analysis approach can yield toxicogenomic models that provide validated and reliable information about the toxicity of compounds. In addition, we provide study design recommendations for genomic studies in toxicology, covering areas of power, sample size, the need for replicates, and the issue of sample pooling.
Source: Springer protocols feed by Pharmacology/Toxicology - October 1, 2008 Category: Drugs & Pharmacology Source Type: info

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The failure of drug candidates during clinical trials due to toxicity, especially hepatotoxicity, is an important and continuing problem in the pharmaceutical industry.
Source: Springer protocols feed by Pharmacology/Toxicology - October 1, 2008 Category: Drugs & Pharmacology Source Type: info

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Reference databases consisting of large sample numbers and high-dimensional microarray data are now available for the investigation of adverse events in animal model systems such as the rat. This large volume of data, accompanied by appropriate study designs, compound and dose selection procedure, and minimization of technical and biological confounding effects, can yield successful predictive models for a variety of hypotheses. The process of training, validating, and implementing predictive models is cyclical and complex. This chapter highlights individual decisions that need to be made before, during, and after a model ...
Source: Springer protocols feed by Pharmacology/Toxicology - October 1, 2008 Category: Drugs & Pharmacology Source Type: info

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“Omics” experiments amass large amounts of data requiring integration of several data sources for data interpretation. For instance, microarray, metabolomic, and proteomic experiments may at most yield a list of active genes, metabolites, or proteins, respectively. More generally, the experiments yield active features that represent subsequences of the gene, a chemical shift within a complex mixture, or peptides, respectively. Thus, in the best-case scenario, the investigator is left to identify the functional significance, but more likely the investigator must first identify the larger context of the feature (...
Source: Springer protocols feed by Pharmacology/Toxicology - October 1, 2008 Category: Drugs & Pharmacology Source Type: info

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Genomics-based tools, such as microarrays, do appear to offer promise in evaluating the relevance of one species to another in terms of molecular and cellular response to a given treatment. However, to fulfill this promise the individual end points (i.e., the genes, proteins, or mRNAs) measured in one species must be mapped to corresponding end points in another species. Several approaches, along with their strengths and weaknesses, are described in this chapter. A sequential approach is described that first makes use of a “Genome To Genome Through Orthology” method, where probe sequences for a given species ar...
Source: Springer protocols feed by Pharmacology/Toxicology - October 1, 2008 Category: Drugs & Pharmacology Source Type: info

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In the area of toxicology, the subdiscipline of toxicogenomics has emerged, which is the use of genome-scale mRNA expression profiling to monitor responses to adverse xenobiotic exposure. Toxicogenomics is being investigated for use in the triage of compounds through predicting potential toxicity, defining mechanisms of toxicity, and identifying potential biomarkers of toxicity. Whereas various approaches have been reported for the development of algorithms predictive of toxicity and for the interpretation of gene expression data for deriving mechanisms of toxicity, there are no clearly defined methods for the discovery of...
Source: Springer protocols feed by Pharmacology/Toxicology - October 1, 2008 Category: Drugs & Pharmacology Source Type: info

From Pharmacogenomics to Translational BiomarkersEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
There is a need for new biomarkers to enable faster detection of adverse events due to drugs and disease processes. One would prefer biomarkers that are useful in multiple species (i.e., translational or bridging biomarkers) so that it would be possible to directly link responses between species and follow such injury in both preclinical and clinical settings. This chapter will explore some of the issues surrounding the use of pharmacogenomics to identify and qualify such biomarkers, and examples will be provided.
Source: Springer protocols feed by Pharmacology/Toxicology - July 11, 2008 Category: Drugs & Pharmacology Source Type: info

Public Consortium Efforts in ToxicogenomicsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Public consortia provide a forum for addressing questions requiring more resources than one organization alone could bring to bear and engaging many sectors of the scientific community. They are particular well suited for tackling some of the questions encountered in the field of toxicogenomics, where the number of studies and microarray analyses would be prohibitively expensive for a single organization to carry out. Five consortia that stand out in the field of toxicogenomics are the Institutional Life Sciences Institute (ILSI) Health and Environmental Sciences Institute (HESI) Committee on the Application of Genomics to...
Source: Springer protocols feed by Pharmacology/Toxicology - July 11, 2008 Category: Drugs & Pharmacology Source Type: info

Applications of Toxicogenomics to Nonclinical Drug Development: Regulatory Science ConsiderationsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Scientists in the pharmaceutical industry have ready access to samples from animal toxicology studies carefully designed to test the safety characteristics of a steady pipeline of agents advancing toward clinical testing. Applications of toxicogenomics to the evaluation of compounds could best be realized if this promising technology could be implemented in these studies fully anchored in the traditional study end points currently used to characterize phenotypic outcome and to support the safe conduct of clinical testing. Regulatory authorities worldwide have declared their support for toxicogenomics and related technologi...
Source: Springer protocols feed by Pharmacology/Toxicology - July 11, 2008 Category: Drugs & Pharmacology Source Type: info

Use of Traditional End Points and Gene Dysregulation to Understand Mechanisms of Toxicity: Toxicogenomics in Mechanistic ToxicologyEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Microarray technologies can be used to generate massive amounts of gene expression information as an initial step to decipher the molecular mechanisms of toxicologic changes. Identifying genes whose expression is associated with specific toxic end points is an initial step in predicting, characterizing, and understanding toxicity. Analysis of gene function and the chronology of gene expression changes represent additional methods to generate hypotheses of the mechanisms of toxicity. Follow-up experiments are typically required to confirm or refute hypotheses derived from toxicogenomic data. Understanding the mechanism of t...
Source: Springer protocols feed by Pharmacology/Toxicology - July 11, 2008 Category: Drugs & Pharmacology Source Type: info

Quality Control of Microarray Assays for Toxicogenomic and In Vitro Diagnostic ApplicationsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The generation of high-quality microarray data for toxicogenomics can be affected by the study design and methods used for sample acquisition, preparation, and processing. Bias can be introduced during animal treatment, tissue handling, and sample preparation. Metrics and controls used in assessing RNA integrity and the quality of microarray sample generation are reviewed in this chapter. Regulations and guidelines involved in the application of microarrays as a commercial in vitro diagnostic device are also described.
Source: Springer protocols feed by Pharmacology/Toxicology - July 11, 2008 Category: Drugs & Pharmacology Source Type: info

Role of Statistics in ToxicogenomicsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In this chapter, we provide a structured approach to the statistical analysis of toxicogenomic data, from the assessment of data quality to data exploration, gene and pathway level analysis, and finally predictive model building. This type of analysis approach can yield toxicogenomic models that provide validated and reliable information about the toxicity of compounds. In addition, we provide study design recommendations for genomic studies in toxicology, covering areas of power, sample size, the need for replicates, and the issue of sample pooling.
Source: Springer protocols feed by Pharmacology/Toxicology - July 11, 2008 Category: Drugs & Pharmacology Source Type: info

Predictive Toxicogenomics in Preclinical DiscoveryEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The failure of drug candidates during clinical trials due to toxicity, especially hepatotoxicity, is an important and continuing problem in the pharmaceutical industry.
Source: Springer protocols feed by Pharmacology/Toxicology - July 11, 2008 Category: Drugs & Pharmacology Source Type: info

In Vivo Predictive ToxicogenomicsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Reference databases consisting of large sample numbers and high-dimensional microarray data are now available for the investigation of adverse events in animal model systems such as the rat. This large volume of data, accompanied by appropriate study designs, compound and dose selection procedure, and minimization of technical and biological confounding effects, can yield successful predictive models for a variety of hypotheses. The process of training, validating, and implementing predictive models is cyclical and complex. This chapter highlights individual decisions that need to be made before, during, and after a model ...
Source: Springer protocols feed by Pharmacology/Toxicology - July 11, 2008 Category: Drugs & Pharmacology Source Type: info

Bioinformatics: Databasing and Gene AnnotationEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
“Omics” experiments amass large amounts of data requiring integration of several data sources for data interpretation. For instance, microarray, metabolomic, and proteomic experiments may at most yield a list of active genes, metabolites, or proteins, respectively. More generally, the experiments yield active features that represent subsequences of the gene, a chemical shift within a complex mixture, or peptides, respectively. Thus, in the best-case scenario, the investigator is left to identify the functional significance, but more likely the investigator must first identify the larger context of the feature (...
Source: Springer protocols feed by Pharmacology/Toxicology - July 11, 2008 Category: Drugs & Pharmacology Source Type: info

Microarray Probe Mapping and Annotation in Cross-Species Comparative ToxicogenomicsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Genomics-based tools, such as microarrays, do appear to offer promise in evaluating the relevance of one species to another in terms of molecular and cellular response to a given treatment. However, to fulfill this promise the individual end points (i.e., the genes, proteins, or mRNAs) measured in one species must be mapped to corresponding end points in another species. Several approaches, along with their strengths and weaknesses, are described in this chapter. A sequential approach is described that first makes use of a “Genome To Genome Through Orthology” method, where probe sequences for a given species ar...
Source: Springer protocols feed by Pharmacology/Toxicology - July 11, 2008 Category: Drugs & Pharmacology Source Type: info

Toxicogenomics in Biomarker DiscoveryEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In the area of toxicology, the subdiscipline of toxicogenomics has emerged, which is the use of genome-scale mRNA expression profiling to monitor responses to adverse xenobiotic exposure. Toxicogenomics is being investigated for use in the triage of compounds through predicting potential toxicity, defining mechanisms of toxicity, and identifying potential biomarkers of toxicity. Whereas various approaches have been reported for the development of algorithms predictive of toxicity and for the interpretation of gene expression data for deriving mechanisms of toxicity, there are no clearly defined methods for the discovery of...
Source: Springer protocols feed by Pharmacology/Toxicology - July 11, 2008 Category: Drugs & Pharmacology Source Type: info

Toxicogenomics and Classic Toxicology: How to Improve Prediction and Mechanistic Understanding of Human ToxicityEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The field of toxicogenomics has been advancing during the past decade or so since its origin. Most pharmaceutical companies are using it in one or more ways to improve their productivity and supplement their classic toxicology studies. Acceptance of toxicogenomics will continue to grow as regulatory concerns are addressed, proof of concept studies are disseminated more fully, and internal case studies show value for the use of this new technology in concert with classic testing.
Source: Springer protocols feed by Pharmacology/Toxicology - July 11, 2008 Category: Drugs & Pharmacology Source Type: info

Gene Expression-Based Biomarkers of Drug SafetyEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Large-scale gene expression profiling with microarray platforms represents a new approach to identify much needed, novel mechanism-based biomarkers of toxicity for use in preclinical and clinical studies. These biomarkers may have diagnostic and/or predictive values and may consist of single gene products or of gene sets or gene expression signatures. Derivation and validation of these molecular markers involves supervised classification methods of reference data with sophisticated statistical methodologies. In this chapter, we review the methods for the identification and development of toxicity biomarkers with gene expre...
Source: Springer protocols feed by Pharmacology/Toxicology - March 10, 2008 Category: Drugs & Pharmacology Source Type: info

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