MedWorm.com provides a medical RSS filtering service. Over 6000 RSS medical sources are combined and output via different filters. This feed contains the latest items from the 'Current Pharmaceutical Biotechnology' source. Mon, 15 Mar 2010 16:39:21 +0100 http://www.medworm.com/index.php?rid=3340098&cid=s_37014_70_f&fid=37014&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20201795%26dopt%3DAbstract Authors: Elman NM, Upadhyay UM Drug delivery microdevices based on MEMS (Micro-Electro-Mechanical-Systems) represent the next generation of active implantable drug delivery systems. MEMS technology has enabled the scaling down of current delivery modalities to the micrometer and millimeter size. The complementary use of biocompatible materials makes this technology potentially viable for a wide variety of clinical applications. Conditions such as brain tumors, chronic pain syndromes, and infectious abscess represent specialized clinical diseases that will likely benefit most from such drug delivery microdevices. Designing MEMS microdevices poses considerable technical and clinical challenges as devices need to be constructed from biocompatible materials that are harmless to human tissu... Current Pharmaceutical Biotechnology journals http://www.medworm.com/rss/comments.php?id=3340098 Thu, 04 Mar 2010 00:00:00 +0100 3340098 http://www.medworm.com/index.php?rid=3340097&cid=s_37014_70_f&fid=37014&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20201796%26dopt%3DAbstract Authors: Van Lehn RC, Sing CE, Chen H, Alexander-Katz A Targeted drug delivery has traditionally relied on finding highly specific biochemical markers at a target location. However, recent developments in this area have shown that purely physical and physicochemical factors are as important and can be used to aid in the targeting process. Here, we review the physicochemical factors affecting the targeting and delivery process and their relation to established biochemical markers. We refer to this combined approach as multidimensional targeting (MDT). More specifically, we examine the role of MDT factors across different length scales of relevance to the drug delivery pathway. Finally, we conclude with our perspective on the future of this burgeoning area. PMID: 20201796 [PubMed - a... Current Pharmaceutical Biotechnology journals http://www.medworm.com/rss/comments.php?id=3340097 Thu, 04 Mar 2010 00:00:00 +0100 3340097 http://www.medworm.com/index.php?rid=3336172&cid=s_37014_70_f&fid=37014&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20199378%26dopt%3DAbstract Authors: Nathan M Implanted medical devices (IMDs), in particular neuro-stimulators, drug delivery chips and cochlear implants are undergoing miniaturization. Some of these miniaturized IMDs are "active" in the sense that they require a power source for operation. In most cases, the ideal power source needs to be an implanted battery of dimensions similar to that of the device. The state-of-the-art of battery miniaturization is reviewed with emphasis on novel Li and Li-ion two- and three-dimensional thin-film microbatteries. It is shown that three-dimensional thin-film batteries may provide a solution to the power requirements of miniaturized IMDs. PMID: 20199378 [PubMed - as supplied by publisher] (Source: Current Pharmaceutical Biotechnology) Current Pharmaceutical Biotechnology journals http://www.medworm.com/rss/comments.php?id=3336172 Thu, 04 Mar 2010 00:00:00 +0100 3336172 http://www.medworm.com/index.php?rid=3336171&cid=s_37014_70_f&fid=37014&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20199379%26dopt%3DAbstract Authors: Wang Z, Chocat N In the past decade, novel fiber structures and material compositions have led to the introduction of new diagnostic and therapeutic tools. We review the structure, the material composition and the fabrication processes behind these novel fiber systems. Because of their structural flexibility, their compatibility with endoscopic appliances and their efficiency in laser delivery, these fiber systems have greatly extended the reach of a wide range of surgical lasers in minimally invasive procedures. Much research in novel fiber-optics delivery systems has been focused on the accommodation of higher optical powers and the extension to a broader wavelength range. Until recently, CO(2) laser surgery, renowned for its precision and efficiency, was limited to open sur... Current Pharmaceutical Biotechnology journals http://www.medworm.com/rss/comments.php?id=3336171 Thu, 04 Mar 2010 00:00:00 +0100 3336171 http://www.medworm.com/index.php?rid=3336170&cid=s_37014_70_f&fid=37014&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20199380%26dopt%3DAbstract We describe the chip outline as well as the basic modeling scheme of such sensors. We discuss the highlights and problems of such system, from the point of view of micro-system-technology. PMID: 20199380 [PubMed - as supplied by publisher] (Source: Current Pharmaceutical Biotechnology) Current Pharmaceutical Biotechnology journals http://www.medworm.com/rss/comments.php?id=3336170 Thu, 04 Mar 2010 00:00:00 +0100 3336170 http://www.medworm.com/index.php?rid=3336169&cid=s_37014_70_f&fid=37014&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20199381%26dopt%3DAbstract Authors: Rosen Y, Gurman P There are conditions in clinical medicine demanding critical therapeutic decisions. These conditions necessitate accuracy, rapidity, accessibility, cost-effectiveness and mobility. New technologies have been developed in order to address these challenges. Microfluidics and Micro Electro-Mechanical Systems are two of such technologies. Microfluidics, a discipline that involves processing fluids at the microscale in etched microchannels, is being used to build lab- on-a-chip systems to run chemical and biological assays. These systems are being transformed into handheld devices designed to be used at remote settings or at the bedside. MEMS are microscale electromechanical elementsintegrated in lab chip systems or used as individual components. MEMS based sensor... Current Pharmaceutical Biotechnology journals http://www.medworm.com/rss/comments.php?id=3336169 Thu, 04 Mar 2010 00:00:00 +0100 3336169 http://www.medworm.com/index.php?rid=3336168&cid=s_37014_70_f&fid=37014&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20199382%26dopt%3DAbstract Authors: Grattoni A, Fine D, Ziemys A, Gill J, Zabre E, Goodall R, Ferrari M Significant recent progress has been made in the development of microfabricated nanofluidic devices for use in the biomedical sciences. Novel nanotechnological approaches have been explored in view of a more individualized medical approach. Much of the development has been fuelled by the advantages derived from utilizing nanoscale phenomena to manipulate fluid samples or mediate drug delivery. As such, we present a comprehensive review of nanochannel technologies, highlighting their potential for diagnostic and therapeutic applications. PMID: 20199382 [PubMed - as supplied by publisher] (Source: Current Pharmaceutical Biotechnology) Current Pharmaceutical Biotechnology journals http://www.medworm.com/rss/comments.php?id=3336168 Thu, 04 Mar 2010 00:00:00 +0100 3336168 http://www.medworm.com/index.php?rid=3336167&cid=s_37014_70_f&fid=37014&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20199383%26dopt%3DAbstract Authors: Chye S, Loo J, Moore T, Banik B, Alexis F Nanotechnologies have the potential to improve current disease diagnosis due to their ability to circulate in the blood and distribute in the body to image tissues and cells or therapeutical applications to deliver a payload. Among nanoparticles with different materials composition, inorganic nanoparticles composed of calcium phosphate have numerous advantages including ease of synthesis, control of physico-chemical properties, strong interactions with their payload, and biocompatibility. In this review we discuss the different routes of synthesis of calcium phosphate nanoparticles, novel systems, strategies to load agents, biostability and cytotoxicity, biodistribution and pharmacokinetics, bio-imaging and therapeutical applications. ... Current Pharmaceutical Biotechnology journals http://www.medworm.com/rss/comments.php?id=3336167 Thu, 04 Mar 2010 00:00:00 +0100 3336167 http://www.medworm.com/index.php?rid=3312093&cid=s_37014_70_f&fid=37014&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20170473%26dopt%3DAbstract Authors: Arawaka S, Machiya Y, Kato T The most characteristic feature of neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis and Huntington's disease, is the occurrence of extra- or intracellular fibrillar aggregates containing misfolded proteins with beta-sheet conformation. These aggregates are composed of distinct proteins in each neurodegenerative disease. However, mutations in genes encoding major constituents of aggregates, such as Abeta, tau, alpha-synuclein, SOD1 and huntingtin, have been identified to causally associate with familial forms of the diseases. Biochemical studies demonstrate that these mutant and some wild-type proteins tend to be misfolded or form aggregates. It has been proposed that these diseases are ca... Current Pharmaceutical Biotechnology journals http://www.medworm.com/rss/comments.php?id=3312093 Tue, 16 Feb 2010 00:00:00 +0100 3312093 http://www.medworm.com/index.php?rid=3312092&cid=s_37014_70_f&fid=37014&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20170474%26dopt%3DAbstract Authors: Tutar L, Tutar Y Heat shock proteins (Hsps) protect protein substrates against conformational damage to promote the function of the proteins, prevent aggregation and prevent formation of toxic inclusion bodies. Protein aggregates and fibrils have been associated with neurodegenerative diseases and with inclusion bodies. High-level expression of recombinant protein for biotechnological purposes often leads to insoluble inclusion bodies. Therefore, misfolded proteins must be properly folded or must be degraded through heat shock protein action. This function protects cells against cytotoxic outcomes. In addition to their cytoprotective roles, Hsps are involved in other functions since Hsps exist in all types of cells and tissues. Therefore, several diseases are associated with a... Current Pharmaceutical Biotechnology journals http://www.medworm.com/rss/comments.php?id=3312092 Tue, 16 Feb 2010 00:00:00 +0100 3312092 http://www.medworm.com/index.php?rid=3291387&cid=s_37014_70_f&fid=37014&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20166961%26dopt%3DAbstract Authors: Sajjad MU, Samson B, Wyttenbach A Intra- and extracellular protein misfolding and aggregation is likely to contribute to a number of age-related central nervous system diseases ("proteinopathies"). Therefore, molecular chaperones, such as heat shock proteins (HSPs), that regulate protein folding, misfolding and adaption to cellular stress are emerging as therapeutic targets. Here we review the current knowledge of HSP-modulating drugs and discuss the opportunities and difficulties of their therapeutic use to treat proteinopathies such as Alzheimer's- and Parkinson's disease, the polyglutamine- and prion disorders and Amyotrophic Lateral Sclerosis. PMID: 20166961 [PubMed - as supplied by publisher] (Source: Current Pharmaceutical Biotechnology) Current Pharmaceutical Biotechnology journals http://www.medworm.com/rss/comments.php?id=3291387 Tue, 16 Feb 2010 00:00:00 +0100 3291387 http://www.medworm.com/index.php?rid=3291386&cid=s_37014_70_f&fid=37014&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20166962%26dopt%3DAbstract Authors: Nagai Y, Fujikake N, Popiel HA, Wada K Protein misfolding and aggregation in the brain have been implicated as a common molecular pathogenesis of various neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and the polyglutamine (polyQ) diseases. The polyQ diseases are a group of nine hereditary neurodegenerative diseases, including Huntington's disease (HD) and various types of spinocerebellar ataxia (SCA), which are caused by abnormal expansions of the polyQ stretch (> 35-40 repeats) in unrelated disease-causative proteins. The expanded polyQ stretch is thought to trigger misfolding of these proteins, leading to their aggregation and accumulation as inclusion bodies in affected neurons, eventually resulting in neuro... Current Pharmaceutical Biotechnology journals http://www.medworm.com/rss/comments.php?id=3291386 Tue, 16 Feb 2010 00:00:00 +0100 3291386 http://www.medworm.com/index.php?rid=3291385&cid=s_37014_70_f&fid=37014&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20166963%26dopt%3DAbstract Authors: Luo GR, Le WD The homeostasis of the protein synthesis and degradation is crucial for cell survival. Most age-related neurodegenerative diseases are characterized by accumulation of aberrant protein aggregates in affected brain regions. The principal routes of intracellular protein metabolism are the ubiquitin proteasome system (UPS) and the autophagy-lysosome pathway (ALP). They collaborate to degrade wasted proteins and interact each other to cope with the pathological conditions, in which molecular chaperones play collective roles by assisting the protein targeting to the proteasome or autophagy. It is known that intracellular protein degradation functions are decreased with aging in many tissues and organs. Failure to perform their functions could underlie the inability of... Current Pharmaceutical Biotechnology journals http://www.medworm.com/rss/comments.php?id=3291385 Tue, 16 Feb 2010 00:00:00 +0100 3291385 http://www.medworm.com/index.php?rid=3291384&cid=s_37014_70_f&fid=37014&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20166964%26dopt%3DAbstract Authors: Radhakrishnan K, Hescheler J, Schneider T Screening for protein interaction partners of ion channels helps to elucidate signaling cascades to cellular targets and processes for a better understanding of the origin of diseases. Most important are the cytosolic segments of membrane-bound voltage- and ligand-gated ion channels or from ion channel regulators, which may connect to specific signaling complexes. So far, not much is known about those interactions. Molecular chaperones are proteins, which support the biosynthesis of proteins during maturation without being part of the final protein complex or which support the degradation of targeted proteins within the cellular protein quality control. Heat shock proteins (Hsps) like Hsp70 and Hsp90 are molecular chaperones and were f... Current Pharmaceutical Biotechnology journals http://www.medworm.com/rss/comments.php?id=3291384 Tue, 16 Feb 2010 00:00:00 +0100 3291384 http://www.medworm.com/index.php?rid=3291383&cid=s_37014_70_f&fid=37014&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20166965%26dopt%3DAbstract Authors: Gunnar PD, Dietz H, Lundbeck H Cell-penetrating peptides (CPP), also called protein transduction domains (PTD), membrane-permeable peptides (MPP), or Trojan horse peptides, have been used in many different research areas. The delivery of heat shock proteins (Hsp) using CPP has been applied in models for apoptosis, necrosis, oxidative stress, neurodegenerative diseases, stroke, cystic fibrosis, smooth muscle relaxation, myocardial injury, scar formation, and others. This review summarizes the accomplishments of the field over the last years and discusses why Hsp are particularly suitable for CPP-mediated delivery. PMID: 20166965 [PubMed - as supplied by publisher] (Source: Current Pharmaceutical Biotechnology) Current Pharmaceutical Biotechnology journals http://www.medworm.com/rss/comments.php?id=3291383 Tue, 16 Feb 2010 00:00:00 +0100 3291383 http://www.medworm.com/index.php?rid=3291382&cid=s_37014_70_f&fid=37014&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20166966%26dopt%3DAbstract Authors: Laskowska E, Matuszewska E, Kuczyńska-Wiśnik D Small heat shock proteins (sHsps) are molecular chaperones ubiquitously distributed in numerous species, from bacteria to humans. A conserved C-terminal "alpha-crystallin" domain organized in a beta-sheet sandwich and oligomeric structure are common features of sHsps. sHsps protect cells against many kinds of stresses including heat shock, oxidative and osmotic stress. sHsps recognize unfolded proteins, prevent their irreversible aggregation and facilitate refolding of bound substrates in cooperation with ATP-dependent molecular chaperones (Hsp70/Hsp40). Mammalian sHsps (HSPBs) are multifunctional proteins involved in many cellular processes including those which are not directly related to protein folding and aggregat... Current Pharmaceutical Biotechnology journals http://www.medworm.com/rss/comments.php?id=3291382 Tue, 16 Feb 2010 00:00:00 +0100 3291382 http://www.medworm.com/index.php?rid=3291381&cid=s_37014_70_f&fid=37014&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20166967%26dopt%3DAbstract Authors: Dancsó B, Spiró Z, Arslan MA, Nguyen MT, Papp D, Csermely P, Sőti C Molecular chaperones and the heat shock response guard and modulate protein conformation, protect proteins from misfolding and aggregation, and maintain signalling and organellar networks. Overnutrition and the metabolic syndrome represent a pro-aging condition, and dietary restriction is the most robust environmental intervention that induces longevity from yeast to mammals. In recent years a considerable effort has been made to elucidate the signaling pathways involved in metabolic signaling. Here we review the current understanding on the connection between metabolic stress, dietary restriction and the heat shock response and highlight results showing chaperone induction as a promising thera... Current Pharmaceutical Biotechnology journals http://www.medworm.com/rss/comments.php?id=3291381 Tue, 16 Feb 2010 00:00:00 +0100 3291381 http://www.medworm.com/index.php?rid=3033804&cid=s_37014_70_f&fid=37014&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19939212%26dopt%3DAbstract Authors: Sanodiya BS, Thakur GS, Baghel RK, Prasad G, Bisen PS Ganoderma lucidum (Ling Zhi) is a basidiomycete white rot macrofungus which has been used extensively as "the mushroom of immortality" in China, Japan, Korea and other Asian countries for 2000 years. A great deal of work has been carried out on therapeutic potential of Ganoderma lucidum. The basidiocarp, mycelia and spores of Ganoderma lucidum contain approximately 400 different bioactive compounds, which mainly include triterpenoids, polysaccharides, nucleotides, sterols, steroids, fatty acids, proteins/peptides and trace elements which has been reported to have a number of pharmacological effects including immunomodulation, anti-atherosclerotic, anti-inflammatory, analgesic, chemo-preventive, antitumor, chemo and radio pr... Current Pharmaceutical Biotechnology journals http://www.medworm.com/rss/comments.php?id=3033804 Fri, 27 Nov 2009 17:00:17 +0100 3033804 http://www.medworm.com/index.php?rid=3033803&cid=s_37014_70_f&fid=37014&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19939213%26dopt%3DAbstract Authors: Li YM, Jiang JG, Yang L, Wang DY Wikstroemia indica (L.) C. A. Mey. is a member of family Thymelaeaceae and mainly distributes in middle and southeast part of China. As a traditional Chinese herb, this plant has long been employed as antipyretics, detoxicants, expectorants, vermifuges as well as aborticides in clinic practice. However, its use has mainly been based on empirical findings during hundreds and thousands of years. Recent studies indicated that W. indica contains abundant active components including flavonoids, biflavonoids, coumarins, lignans, volatile oils, polysaccharides etc. This paper provides a comprehensive review of pharmacological relevant compounds of W. indica that have been characterized to date, and introduce the research progresses supporting its phar... Current Pharmaceutical Biotechnology journals http://www.medworm.com/rss/comments.php?id=3033803 Fri, 27 Nov 2009 17:00:15 +0100 3033803 http://www.medworm.com/index.php?rid=3033802&cid=s_37014_70_f&fid=37014&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19939214%26dopt%3DAbstract Authors: Sun X, Zhu L, Yang G, Sun S, Quan R, Dai W, Li B, Chen C, Li Z Glycan-protein interactions play important biological roles in biological processes. Although there are some methods such as glycan arrays that may elucidate recognition events between carbohydrates and protein as well as screen the important glycan-binding proteins, there is a lack of simple effectively separate method to purify them from complex samples. In proteomics studies, fractionation of samples can help to reduce their complexity and to enrich specific classes of proteins for subsequent downstream analyses. Herein, a rapid simple method for purification of glycan-binding proteins from proteomic samples was developed using hydroxyl-coated magnetic particles coupled with underivatized carbohydrate. Firstly, ... Current Pharmaceutical Biotechnology journals http://www.medworm.com/rss/comments.php?id=3033802 Fri, 27 Nov 2009 17:00:12 +0100 3033802 http://www.medworm.com/index.php?rid=3033801&cid=s_37014_70_f&fid=37014&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19939215%26dopt%3DAbstract This study demonstrates that arginine is a highly effective solvent additive which significantly reduces the light induced aggregation of four IgG1 type monoclonal antibodies (named as IMC-1A, IMC-1B, IMC-1C and IMC-1D) as measured by size exclusion chromatography. All experiments were performed in a phosphate buffer system containing either sodium chloride or arginine hydrochloride. The protein samples were exposed to light in a photo chamber according to ICH (International Conference on Harmonization) guidelines. Thermal unfolding transition temperature (T(m)) of IMC-1A as determined by differential scanning calorimetry (DSC) was significantly decreased ( approximately 3.3 degrees C) in the presence of arginine hydrochloride as compared to in sodium chloride. However, a noticeable increa... Current Pharmaceutical Biotechnology journals http://www.medworm.com/rss/comments.php?id=3033801 Fri, 27 Nov 2009 17:00:09 +0100 3033801 http://www.medworm.com/index.php?rid=3033800&cid=s_37014_70_f&fid=37014&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19939216%26dopt%3DAbstract Authors: Calvo B, Zuñiga L The prime difference between generics and biosimilars is that while generics contain the exact active ingredient as in the originator product, biosimilars are only "similar" and not "identical" to the originator biological medicine. This difference appears due to the nature of the biopharmaceutical medicines which are extremely complex to manufacture (it is not possible to make an exact copy of a biotech medicine in the same way as a traditional chemical molecule can be copied). In fact, it is widely accepted that for biopharmaceuticals, the "process is the product". Minor changes during the manufacturing process can have critical consequences in the patients. The vast majority of the biopharmaceuticals on the market are produced by genetic engineering u... Current Pharmaceutical Biotechnology journals http://www.medworm.com/rss/comments.php?id=3033800 Fri, 27 Nov 2009 17:00:06 +0100 3033800 http://www.medworm.com/index.php?rid=3033808&cid=s_37014_70_f&fid=37014&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19929819%26dopt%3DAbstract Authors: Zhang H, Wang W, Quan C, Fan S Mammalian cell cultivation plays a great role in producing protein therapeutics in the last decades. Many engineering parameters are considered for optimization during process development in mammalian cell cultivation, only shear and mixing are especially highlighted in this paper. It is believed that shear stress due to agitation has been over-estimated to damage cells, but shear may result in nonlethal physiological responses. There is no cell damage in the regions where bubbles form, break up and coalescence, but shear stress becomes significant in the wake of rising bubbles and causes great damage to cells in bubble burst regions. Mixing is not sufficient to provide homogeneous dissolved oxygen tension, pH, CO(2) and nutrients in large-scale ... Current Pharmaceutical Biotechnology journals http://www.medworm.com/rss/comments.php?id=3033808 Mon, 23 Nov 2009 00:00:00 +0100 3033808 http://www.medworm.com/index.php?rid=3033807&cid=s_37014_70_f&fid=37014&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19929820%26dopt%3DAbstract Authors: Li K, Xiao L, Liu C, Zhang J, Sirois P A variety of technologies can be used in the detection of contagious pathogens. In the early stage of an outbreak of a new infectious disease, rtPCR is advantageous over many other assays. The rtPCR can be developed either using low fidelity DNA polymerase or high fidelity DNA polymerase. The application of high fidelity DNA polymerase allows the shortening of assay development. In addition, the synthesized DNA template used as positive controls is suggested for shortening the time for assay development. Overall comparison of time required for assay development, specificity, and sensitivity for different types of molecular diagnostic technologies, it seems that early confirmation of viral infected patients will be diagnosed primarily with... Current Pharmaceutical Biotechnology journals http://www.medworm.com/rss/comments.php?id=3033807 Mon, 23 Nov 2009 00:00:00 +0100 3033807 http://www.medworm.com/index.php?rid=3033806&cid=s_37014_70_f&fid=37014&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19929821%26dopt%3DAbstract We examined the photophysical properties of the new near infrared (NIR) fluorescent label SeTau-665 on a plasmonic platform of self- assembled colloidal structures (SACS) of silver prepared on a semitransparent silver film. A SeTau-665 immunoassay was performed on this platform and a control glass slide. The fluorescence properties of this label substantially change due to plasmonic interactions. While the average brightness increase of SeTau 665 in ensemble measurements was about 70-fold, fluorescence enhancements up to four-hundred times were observed on certain "hot spots" for single molecule measurements. The intensity increase is strongly correlated with a simultaneous decrease in fluorescence lifetime in these "hot spots". The large increase in brightness allows the reduction of the ... Current Pharmaceutical Biotechnology journals http://www.medworm.com/rss/comments.php?id=3033806 Mon, 23 Nov 2009 00:00:00 +0100 3033806 http://www.medworm.com/index.php?rid=3033805&cid=s_37014_70_f&fid=37014&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19929822%26dopt%3DAbstract Authors: Sakata H, Horiuchi M, Takahashi I, Kinjo M The conversion of prion protein (PrP) from the monomeric cellular isoform to the oligomeric pathological isoform is a crucial event in the pathogenesis of prion diseases. To investigate oligomer formation of PrP, enhanced green fluorescent protein (EGFP)-tagged PrP (EGFP-PrP) without the glycosylphosphatidylinositol (GPI) anchor was prepared and the oligomerization of EGFP-PrP induced by sodium dodecyl sulphate (SDS) was monitored by fluorescence correlation spectroscopy (FCS). The FCS analysis indicated that soluble oligomers were formed at 0.011% SDS. Furthermore, the combination of fluorescence cross-correlation spectroscopy (FCCS) and a panel of anti-PrP monoclonal antibodies (mAbs) revealed the conformational changes in PrP. Our ... Current Pharmaceutical Biotechnology journals http://www.medworm.com/rss/comments.php?id=3033805 Mon, 23 Nov 2009 00:00:00 +0100 3033805 http://www.medworm.com/index.php?rid=3009194&cid=s_37014_70_f&fid=37014&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19916947%26dopt%3DAbstract Authors: Calvo B, Zuñiga L The prime difference between generics and biosimilars is that while generics contain the exact active ingredient as in the originator product, biosimilars are only "similar" and not "identical" to the originator biological medicine. This difference appears due to the nature of the biopharmaceutical medicines which are extremely complex to manufacture (it is not possible to make an exact copy of a biotech medicine in the same way as a traditional chemical molecule can be copied). In fact, it is widely accepted that for biopharmaceuticals, the "process is the product". Minor changes during the manufacturing process can have critical consequences in the patients. The vast majority of the biopharmaceuticals on the market are produced by genetic engineering u... Current Pharmaceutical Biotechnology journals http://www.medworm.com/rss/comments.php?id=3009194 Mon, 16 Nov 2009 00:00:00 +0100 3009194 http://www.medworm.com/index.php?rid=3000757&cid=s_37014_70_f&fid=37014&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19912105%26dopt%3DAbstract Authors: Calvo B, Zuñiga L The prime difference between generics and biosimilars is that while generics contain the exact active ingredient as in the originator product, biosimilars are only "similar" and not "identical" to the originator biological medicine. This difference appears due to the nature of the biopharmaceutical medicines which are extremely complex to manufacture (it is not possible to make an exact copy of a biotech medicine in the same way as a traditional chemical molecule can be copied). In fact, it is widely accepted that for biopharmaceuticals, the "process is the product". Minor changes during the manufacturing process can have critical consequences in the patients. The vast majority of the biopharmaceuticals on the market are produced by genetic engineering u... Current Pharmaceutical Biotechnology journals http://www.medworm.com/rss/comments.php?id=3000757 Mon, 16 Nov 2009 00:00:00 +0100 3000757 http://www.medworm.com/index.php?rid=3000756&cid=s_37014_70_f&fid=37014&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19912106%26dopt%3DAbstract Conclusion: the contemporary utilization of E6-E7 oncoproteins and related mRNA expression showed a more appropriate HPV evaluation in at risk women. The HPV-DNA tests does not distinguish between transient and potentially transforming infection, while the detection of E6-E7 mRNAs could early target the presence of an active HPV infection. PMID: 19912106 [PubMed - as supplied by publisher] (Source: Current Pharmaceutical Biotechnology) Current Pharmaceutical Biotechnology journals http://www.medworm.com/rss/comments.php?id=3000756 Mon, 16 Nov 2009 00:00:00 +0100 3000756 http://www.medworm.com/index.php?rid=3000755&cid=s_37014_70_f&fid=37014&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19912107%26dopt%3DAbstract This study demonstrates that arginine is a highly effective solvent additive which significantly reduces the light induced aggregation of four IgG1 type monoclonal antibodies (named as IMC-1A, IMC-1B, IMC-1C and IMC-1D) as measured by size exclusion chromatography. All experiments were performed in a phosphate buffer system containing either sodium chloride or arginine hydrochloride. The protein samples were exposed to light in a photo chamber according to ICH (International Conference on Harmonization) guidelines. Thermal unfolding transition temperature (T(m)) of IMC-1A as determined by differential scanning calorimetry (DSC) was significantly decreased ( approximately 3.3 degrees C) in the presence of arginine hydrochloride as compared to in sodium chloride. However, a noticeable increa... Current Pharmaceutical Biotechnology journals http://www.medworm.com/rss/comments.php?id=3000755 Mon, 16 Nov 2009 00:00:00 +0100 3000755 http://www.medworm.com/index.php?rid=3000754&cid=s_37014_70_f&fid=37014&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19912108%26dopt%3DAbstract Authors: Sun X, Yang G, Sun S, Quan R, Dai W, Li B, Chen C, Li Z Glycan-protein interactions play important biological roles in biological processes. Although there are some methods such as glycan arrays that may elucidate recognition events between carbohydrates and protein as well as screen the important glycan-binding proteins, there is a lack of simple effectively separate method to purify them from complex samples. In proteomics studies, fractionation of samples can help to reduce their complexity and to enrich specific classes of proteins for subsequent downstream analyses. Herein, a rapid simple method for purification of glycan-binding proteins from proteomic samples was developed using hydroxyl-coated magnetic particles coupled with underivatized carbohydrate. Firstly, the epo... Current Pharmaceutical Biotechnology journals http://www.medworm.com/rss/comments.php?id=3000754 Mon, 16 Nov 2009 00:00:00 +0100 3000754 http://www.medworm.com/index.php?rid=3000753&cid=s_37014_70_f&fid=37014&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19912109%26dopt%3DAbstract Authors: Li YM, Jiang JG, Yang L, Wang DY Wikstroemia indica (L.) C. A. Mey. is a member of family Thymelaeaceae and mainly distributed in middle and southeast part of China. As a traditional Chinese herb, this plant has long been employed as antipyretics, detoxicants, expectorants, vermifuges as well as aborticides in clinic practice. However, its use has mainly been based on empirical findings during hundreds and thousands of years. Recent studies indicated that W. indica contains abundant active components including flavonoids, biflavonoids, coumarins, lignans, volatile oils, polysaccharides etc. This paper provides a comprehensive review of pharmacological relevant compounds of W. indica that have been characterized to date, and introduce the research progresses supporting its phar... Current Pharmaceutical Biotechnology journals http://www.medworm.com/rss/comments.php?id=3000753 Mon, 16 Nov 2009 00:00:00 +0100 3000753 http://www.medworm.com/index.php?rid=2797529&cid=s_37014_70_f&fid=37014&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19751176%26dopt%3DAbstract Authors: Pandey RS, Dixit VK Immune stimulating complexes (ISCOMs) incorporating recombinant hepatitis B surface antigen (rHBsAg) were prepared for induction of humoral and cellular immunity by subcutaneous administration. Prepared ISCOMs were characterized for their size, shape, incorporation efficiency, zeta potential, antigen integrity, antigen conformation and immunogenicity by biophysical and immunological techniques including transmission electron microscopy (TEM), Dynamic light scattering (DLS), SDS-PAGE, fluorescence spectroscopy, in vitro potency test and in vivo humoral and cellular immune stimulatory efficacy in Balb/c mice. Prepared ISCOM particles show characteristic cage like morphology with average size of 44 approximately nm, polydispersity index 0.1, negative zeta pote... Current Pharmaceutical Biotechnology journals http://www.medworm.com/rss/comments.php?id=2797529 Sat, 12 Sep 2009 23:00:00 +0100 2797529 http://www.medworm.com/index.php?rid=2797528&cid=s_37014_70_f&fid=37014&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19751177%26dopt%3DAbstract In this study, we identified that the most detrimental single point mutation is from tryptophan to cysteine at the residue position of 452 on ErbB2 receptor by using I-Mutant 2.0, SIFT and PolyPhen programs. The modeled mutant showed less stability than native ErbB2 protein based on both total energy of the mutant and stabilizing residues in the mutant protein. This is due to deviation between the mutant and native ErbB2 having the RMSD of about 2.83A. Further, we found, pertuzumab showed a marginal higher binding affinity with ErbB2 receptor of native and mutant type with a binding free energy of -16.01 kcal/mole each as compared to trastuzumab, showing a binding free energy of -15.26 kcal/mole in ErbB2 of native type. On the contrary, trastuzumab showed a remarkably high binding affinity... Current Pharmaceutical Biotechnology journals http://www.medworm.com/rss/comments.php?id=2797528 Sat, 12 Sep 2009 23:00:00 +0100 2797528 http://www.medworm.com/index.php?rid=2797527&cid=s_37014_70_f&fid=37014&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19751178%26dopt%3DAbstract Authors: Verma PC, Trivedi I, Singh H, Shukla AK, Kumar M, Upadhyay SK, Pandey P, Hans AL, Singh PK A protocol for induction and establishment of Agrobacterium rhizogenes mediated hairy root culture of Gossypium hirsutum was developed through infection with the A4 strain and co-cultivation on hormone-free semi-solid MS medium with B5 vitamins. It resulted in the emergence of hairy roots from the leaf explants, 21 days after infection. The transformation of hairy roots was established by PCR amplification of rol B and rol C genes of the Ri plasmid. All root lines expressed gossypol, although distinct inter-clonal quantitative variations were noticed. Five independent hairy root lines were studied for their growth kinetics as well as gossypol production. The yield potentials of one of th... Current Pharmaceutical Biotechnology journals http://www.medworm.com/rss/comments.php?id=2797527 Sat, 12 Sep 2009 23:00:00 +0100 2797527 http://www.medworm.com/index.php?rid=2797526&cid=s_37014_70_f&fid=37014&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19751179%26dopt%3DAbstract Authors: Athanasios E, Konstantina V, Paraskevi K, Nikolaos N Creatine plays a central role in energy metabolism and is synthesized in the liver, kidney and pancreas. In healthy patients, it is transported via the blood stream to the muscles, heart and brain with high and fluctuating energy demands by the molecule creatine transporter. Creatine, although naturally synthesized in the human body, can be ingested in the form of supplements and is commonly used by athletes. The purpose of this review was to assess the clinical applications of creatine supplementation on paediatrics. Creatine metabolism disorders have so far been described at the level of two synthetic steps, guanidinoacetate N-methyltransferase (GAMT) and arginine: glycine amidinotransferase (AGAT), and at the level of the... Current Pharmaceutical Biotechnology journals http://www.medworm.com/rss/comments.php?id=2797526 Sat, 12 Sep 2009 23:00:00 +0100 2797526 http://www.medworm.com/index.php?rid=2797525&cid=s_37014_70_f&fid=37014&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19751180%26dopt%3DAbstract Authors: Thakur GS, Bag M, Sanodiya BS, Bhadouriya P, Debnath M, Prasad G, Bisen PS Momordica balsamina, African pumpkin (Cucurbitaceae), is a tendril-bearing, wild climber containing wide spectrum of medicinal and nutritional values and has been used as a traditional folk medicine in many countries. The leaves, fruits, seeds, and bark of the plant contains resins, alkaloids, flavonoids, glycosides, steroids, terpenes, cardiac glycoside, saponins having various medicinal importance viz. anti-HIV, anti-plasmodial, shigellocidal, anti-diarrheal, anti-septic, anti-bacterial, anti-viral, anti-inflammatory, anti-microbial, antiviral, hypoglycemic, antioxidant, analgesic and hepatoprotective. The therapeutic agent 'Momordin' is capable of inhibiting the growth of HIV and other viruses. The l... Current Pharmaceutical Biotechnology journals http://www.medworm.com/rss/comments.php?id=2797525 Sat, 12 Sep 2009 23:00:00 +0100 2797525 http://www.medworm.com/index.php?rid=2797524&cid=s_37014_70_f&fid=37014&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19751181%26dopt%3DAbstract Authors: Thakur GS, Bag M, Sanodiya BS, Debnath M, Zacharia A, Bhadouriya P, Prasad G, Bisen PS Chlorophytum borivilianum Santapau & Fernandes (Liliaceae) also known as 'Safed Musli' is a traditional rare Indian medicinal herb which has many therapeutic applications in Ayurvedic, Unani, Homeopathic and Allopathic system of medicine. Its roots (tubers) are widely used for various therapeutic applications. It is used to cure physical illness and weakness, as an aphrodisiac agent and revitalizer, as general sex tonic, remedy for diabetes, arthritis and increasing body immunity, curative for natal and postnatal problems, for rheumatism and joint pains, increase lactation in feeding mothers, as antimicrobial, anti-inflammatory, antitumor agent, also used in diarrhea, dysentery, gonorrhe... Current Pharmaceutical Biotechnology journals http://www.medworm.com/rss/comments.php?id=2797524 Sat, 12 Sep 2009 23:00:00 +0100 2797524 http://www.medworm.com/index.php?rid=2627413&cid=s_37014_70_f&fid=37014&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19619118%26dopt%3DAbstract Authors: Verma PC, Basu V, Gupta V, Saxena G, Ur Rahman L Natural products from plants are of major pharmaceutical and therapeutic importance, several of which are often obtained from the underground parts of the concerned plants. Deviation from standard rules in modern medicines, where instead of a single isolated fraction, a group of naturally occurring components exerts the desired therapeutic effect, was noted in case of Picroliv or Kutkin of Picrorhiza kurroa. "Picroliv" mainly a glucoside, is one such compound, normally obtained from 3 - 4 years old roots and rhizomes of an endangered medicinal plant - Picrorhiza kurroa (kutki) and constitute an important component of many Indian herbal preparations, used mainly for the treatment of a variety of liver ailments. It is an iridoid g... Current Pharmaceutical Biotechnology journals http://www.medworm.com/rss/comments.php?id=2627413 Thu, 23 Jul 2009 06:50:23 +0100 2627413 http://www.medworm.com/index.php?rid=2627412&cid=s_37014_70_f&fid=37014&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19619119%26dopt%3DAbstract In conclusion, the role of MD in preclinical PK-PD studies of oncological drugs has been confirmed and it has provided a strong foundation for further clinical research. PMID: 19619119 [PubMed - as supplied by publisher] (Source: Current Pharmaceutical Biotechnology) Current Pharmaceutical Biotechnology journals http://www.medworm.com/rss/comments.php?id=2627412 Thu, 23 Jul 2009 06:50:21 +0100 2627412 http://www.medworm.com/index.php?rid=2627411&cid=s_37014_70_f&fid=37014&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19619120%26dopt%3DAbstract Authors: Singh BK, Dubey VK Tryparedoxin peroxidase (TryP) is a key enzyme of the trypanothione-dependent metabolism for removal of oxidative stress in leishmania. These enzymes function as antioxidants through their peroxidase and peroxynitrite reductase activities. Inhibitors of this enzyme are presumed to be antilesihmania drugs and structural studies are prerequisite of rational drug design. We have constructed three dimensional structure of TryP of Leishmania infantum using comparative modeling. Structural analysis reveals several interesting features. Moreover, it shows remarkable structural difference with human host glutathione peroxidase, an enzyme involved in similar function and TryP from Leishmania major. PMID: 19619120 [PubMed - as supplied by publisher] (Source: Curre... Current Pharmaceutical Biotechnology journals http://www.medworm.com/rss/comments.php?id=2627411 Thu, 23 Jul 2009 06:50:18 +0100 2627411 http://www.medworm.com/index.php?rid=2627410&cid=s_37014_70_f&fid=37014&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19619121%26dopt%3DAbstract Authors: Maity H, Karkaria C, Davagnino J The purpose of this study was to dramatically enhance the solubility (> 400 fold) and stability of a therapeutic protein (Fibroblast Growth Factor 20) and to perform detailed biophysical characterization for the optimization of its formulation. The solubility of FGF-20 strongly depends on pH, arginine concentration and anions present in a buffer system. In the absence and presence of arginine, solubility was higher at lower pH (5 </= pH </= 6) and then decreased steadily with a minimum solubility at around pH 6.3 and plateaus at around pH 7.5 respectively. For a given pH, the protein was most soluble in arginine-sulfate. The solubility of FGF-20 increases with an increase in arginine-sulfate concentration for a given pH. However, a sal... Current Pharmaceutical Biotechnology journals http://www.medworm.com/rss/comments.php?id=2627410 Thu, 23 Jul 2009 06:50:16 +0100 2627410 http://www.medworm.com/index.php?rid=2627409&cid=s_37014_70_f&fid=37014&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19619122%26dopt%3DAbstract Authors: Enayati M, Ahmad Z, Stride E, Edirisinghe M A method for generating poly(lactic-co-glycolic acid) and polycaprolactone biodegradable particles of different size and shape using a jet generated in an electric field is elucidated. These particles are suitable for use as drug carriers and the method can be developed into a mass production route. The effect of different parameters such as applied voltage, collecting distance, flow rate and polymer concentration on inducing size and shape differences for these particles was studied. It was found that the flow rate, polymer concentration and collecting distance have a significant impact on the size of the generated particles and by changing the collecting distance a systematic reduction in the particle size by at least an order of m... Current Pharmaceutical Biotechnology journals http://www.medworm.com/rss/comments.php?id=2627409 Thu, 23 Jul 2009 06:50:12 +0100 2627409 http://www.medworm.com/index.php?rid=2627408&cid=s_37014_70_f&fid=37014&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19619123%26dopt%3DAbstract We present the strong fluorescence effect, a new 392 nm emission peak appearing after binding of a naphtol-urea inhibitor XIIa to the enzyme epoxide hydrolase (EH), along with the quenching of the EH tryptophan fluorescence. We have studied the quenching of the 392-nm peak (attributed to XIIa bound inside the active center of the enzyme) of the mixture EH +XIIa by various strong transparent inhibitors (competing with XIIa for binding to EH), and measured the corresponding values of the Stern-Volmer constants, K(mix)(SV). Strong EH inhibitors demonstrate different replacement behavior which can be used to distinguish them. We further demonstrate a novel fluorescent assay which allows to distinguish highly potent inhibitors and to visualize the strongest among them. We generated our assay ca... Current Pharmaceutical Biotechnology journals http://www.medworm.com/rss/comments.php?id=2627408 Thu, 23 Jul 2009 06:50:10 +0100 2627408 http://www.medworm.com/index.php?rid=2627407&cid=s_37014_70_f&fid=37014&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19619124%26dopt%3DAbstract Authors: Iversen PL, Aird KM, Wu R, Morse MM, Devi GR Phosphorodiamidate morpholino oligomers (PMO), which have a neutral chemistry, are extensively being used as tools for selective inhibition of gene expression in cell culture models and are currently in human clinical trials. Unlike phosphorothioates (PS ODN) and other charged oligonucleotides, little is known about the uptake characteristics of neutral oligomers. The purpose of this study was to understand the kinetics of PMO transport in cells and correlate with antisense activity. In contrast to primary cells and some transformed cell lines which were uptake permissive, established cancer cell lines showed very poor uptake with an occasional diffuse intracellular pattern. Differential PMO uptake was also observed in immune cells,... Current Pharmaceutical Biotechnology journals http://www.medworm.com/rss/comments.php?id=2627407 Thu, 23 Jul 2009 06:50:08 +0100 2627407 http://www.medworm.com/index.php?rid=2627406&cid=s_37014_70_f&fid=37014&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19619125%26dopt%3DAbstract Authors: Földes-Papp Z, König K, Studier H, Bückle R, Breunig HG, Uchugonova A, Kostner GM The binding of superquencher molecular beacon (SQMB) probes to human single-stranded cellular miRNA-122 targets was detected in various single live cells with femtosecond laser microscopy. For delivery of the SQMB-probes, 3D-nanoprocessing of single cells with sub-15 femtosecond 85 MHz near-infrared laser pulses was applied. Transient nanopores were formed by focusing the laser beam for some milliseconds on the membrane of a single cell in order to import of SQMB-probes into the cells. In single cells of the human liver cell lines Huh-7D12 and IHH that expressed miRNA-122, we measured target binding in the cytoplasm by two-photon fluorescence imaging. We found increased fluorescenc... Current Pharmaceutical Biotechnology journals http://www.medworm.com/rss/comments.php?id=2627406 Thu, 23 Jul 2009 06:50:06 +0100 2627406 http://www.medworm.com/index.php?rid=2549029&cid=s_37014_70_f&fid=37014&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19519408%26dopt%3DAbstract Authors: Gagnon P, Arakawa T PMID: 19519408 [PubMed - in process] (Source: Current Pharmaceutical Biotechnology) Current Pharmaceutical Biotechnology journals http://www.medworm.com/rss/comments.php?id=2549029 Sun, 31 May 2009 23:00:00 +0100 2549029 http://www.medworm.com/index.php?rid=2549028&cid=s_37014_70_f&fid=37014&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19519409%26dopt%3DAbstract Authors: Philo JS, Arakawa T Aggregation or reversible self-association of protein therapeutics can arise through a number of different mechanisms. Five common aggregation mechanisms are described and their relations to manufacturing processes to suppress and remove aggregates are discussed. PMID: 19519409 [PubMed - in process] (Source: Current Pharmaceutical Biotechnology) Current Pharmaceutical Biotechnology journals http://www.medworm.com/rss/comments.php?id=2549028 Sun, 31 May 2009 23:00:00 +0100 2549028 http://www.medworm.com/index.php?rid=2549027&cid=s_37014_70_f&fid=37014&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19519410%26dopt%3DAbstract Authors: Kaliyaperumal A, Jing S Assessment of immunogenicity is a major aspect in evaluating the safety of biological therapeutic proteins. It is important to evaluate the immunogenic potential of the biologics in an appropriate fashion using clearly defined strategy and clinical trials. The studies must include the appropriate risk assessment procedures using validated methods. The immune responses against the therapeutic biologics can be studied using various methodologies. These include enzyme linked immunoassays (ELISA), surface plasmon resonance (SPR), chemiluminescence, and flowcytometry assays for binding antibodies and cell based assays for neutralizing antibodies. The immune responses to the biologics can widely vary in various cross section of the population, thus a combinat... Current Pharmaceutical Biotechnology journals http://www.medworm.com/rss/comments.php?id=2549027 Sun, 31 May 2009 23:00:00 +0100 2549027 http://www.medworm.com/index.php?rid=2549026&cid=s_37014_70_f&fid=37014&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19519411%26dopt%3DAbstract Authors: Philo JS Although size exclusion chromatography (SEC) has been, and will continue to be, the primary analytical tool for characterization of the content and size distribution of non-particulate aggregates in protein pharmaceuticals, regulatory concerns are driving increased use of alternative and complementary methods such as analytical ultracentrifugation and light scattering techniques. This review will highlight and critically review the capabilities, advantages, and drawbacks of SEC, analytical ultracentrifugation, and light scattering methods for characterizing aggregates with sizes below about 0.3 microns. The physical principles of the biophysical methods are briefly described and examples of data for real samples and how that data is interpreted are given to help clari... Current Pharmaceutical Biotechnology journals http://www.medworm.com/rss/comments.php?id=2549026 Sun, 31 May 2009 23:00:00 +0100 2549026 http://www.medworm.com/index.php?rid=2549025&cid=s_37014_70_f&fid=37014&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19519412%26dopt%3DAbstract This article will focus on methods for analyzing and quantitating sub visible particles (SbVP) of 2 microns or larger. At the present time there is no routine method for quantitating sub visible particles (SbVP) between 0.1 microns and 2 microns. The most common technique for quantitating the amount of subvisible particles between 2 and 100 microns is the light obscuration method. This technique can determine size and amount of particles, but cannot differentiate between the types of particles, such as protein particles, foreign material, micro bubbles or silicone oil droplets, that can be present in protein solutions. The difficulties in adapting this method, originally developed for small molecule drugs for IV administration, to protein therapeutics delivered subcutaneously is discussed.... Current Pharmaceutical Biotechnology journals http://www.medworm.com/rss/comments.php?id=2549025 Sun, 31 May 2009 23:00:00 +0100 2549025 http://www.medworm.com/index.php?rid=2549024&cid=s_37014_70_f&fid=37014&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19519413%26dopt%3DAbstract Authors: Cao S, Pollastrini J, Jiang Y Field flow fractionation (FFF) is a technique that holds great promise for the analysis and characterization of protein aggregates and particles, due to its wide dynamic range and matrix-free separation mechanism. FFF can be routinely used to achieve good monomer-oligomer separation and quantification for a variety of protein types, and is a reasonable choice for an orthogonal method for size exclusion chromatography and analytical ultracentrifugation. Quantifying sub-micrometer particles in protein therapeutics is a potential of the FFF technique that is yet to be realized, due to the lack of detection with sufficient sensitivity. In this article the effect of several important parameters on the optimization of FFF analyses are explored, and the ... Current Pharmaceutical Biotechnology journals http://www.medworm.com/rss/comments.php?id=2549024 Sun, 31 May 2009 23:00:00 +0100 2549024 http://www.medworm.com/index.php?rid=2549023&cid=s_37014_70_f&fid=37014&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19519414%26dopt%3DAbstract Authors: Li CH, Li T Aggregation is often the major issue during formulation and manufacturing development of therapeutic proteins, in particular human monoclonal antibody. Currently, there is a lack of structural information of aggregates of such large protein as human antibodies, due to the large molecular sizes of the aggregates. In this article, we shall discuss the application of vibrational spectroscopies including FT-IR, Raman and Raman Optical Activity (ROA), to characterize the structures of various types of monoclonal antibody aggregates formed under different stresses. Two different classes of human monoclonal antibodies, namely IgG1 and IgG2, have been subjected to this structural investigation. The common stresses leading to antibody aggregation, mis-folding or unfolding d... Current Pharmaceutical Biotechnology journals http://www.medworm.com/rss/comments.php?id=2549023 Sun, 31 May 2009 23:00:00 +0100 2549023 http://www.medworm.com/index.php?rid=2549022&cid=s_37014_70_f&fid=37014&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19519415%26dopt%3DAbstract Authors: Hamada H, Arakawa T, Shiraki K This paper overviews solution additives that affect protein stability and aggregation during refolding, heating, and freezing processes. Solution additives are mainly grouped into two classes, i.e., protein denaturants and stabilizers. The former includes guanidine, urea, strong ionic detergents, and certain chaotropic salts; the latter includes certain amino acids, sugars, polyhydric alcohols, osmolytes, and kosmotropic salts. However, there are solution additives that are not unambiguously placed into these two classes, including arginine, certain divalent cation salts (e.g., MgCl(2)) and certain polyhydric alcohols (e.g., ethylene glycol). Certain non-ionic or non-detergent surfactants, ionic liquids, amino acid derivatives, polyamines, and ce... Current Pharmaceutical Biotechnology journals http://www.medworm.com/rss/comments.php?id=2549022 Sun, 31 May 2009 23:00:00 +0100 2549022 http://www.medworm.com/index.php?rid=2549021&cid=s_37014_70_f&fid=37014&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19519416%26dopt%3DAbstract This article aims at giving a brief overview about the discovery of the arginine effect, the range of its applications that have been explored over the past two decades, and of the current state of the discussion regarding the mechanisms responsible for the action of L-arginine as suppressor of aggregation. PMID: 19519416 [PubMed - in process] (Source: Current Pharmaceutical Biotechnology) Current Pharmaceutical Biotechnology journals http://www.medworm.com/rss/comments.php?id=2549021 Sun, 31 May 2009 23:00:00 +0100 2549021 http://www.medworm.com/index.php?rid=2549020&cid=s_37014_70_f&fid=37014&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19519417%26dopt%3DAbstract Authors: Nakakido M, Kudou M, Arakawa T, Tsumoto K In spite of its wide application to protein refolding, purification, and storage, we have not yet addressed a general solution to the mechanism of the effects of arginine hydrochloride on proteins. To elucidate the mechanism of the effects on proteins, several attempts have been reported. In this review, we would review the attempts from thermodynamic and kinetic viewpoints. PMID: 19519417 [PubMed - in process] (Source: Current Pharmaceutical Biotechnology) Current Pharmaceutical Biotechnology journals http://www.medworm.com/rss/comments.php?id=2549020 Sun, 31 May 2009 23:00:00 +0100 2549020 http://www.medworm.com/index.php?rid=2549019&cid=s_37014_70_f&fid=37014&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19519418%26dopt%3DAbstract Authors: Yigzaw Y, Hinckley P, Hewig A, Vedantham G Clearance of product related aggregates in therapeutic proteins is a major focus of purification process development. A typical purification process will have one or two chromatographic steps that remove these product related aggregates to an acceptable level. Both cation exchange and anion exchange chromatography can provide robust clearance of aggregates. The primary factors that are critical for aggregate clearance are: resin chemistry, binding and elution condition, peak collection and column load factor. This review covers how these factors can be optimized to increase the effectiveness of ion exchange chromatography in removing aggregates. PMID: 19519418 [PubMed - in process] (Source: Current Pharmaceutical Biotechnology) Current Pharmaceutical Biotechnology journals http://www.medworm.com/rss/comments.php?id=2549019 Sun, 31 May 2009 23:00:00 +0100 2549019 http://www.medworm.com/index.php?rid=2549018&cid=s_37014_70_f&fid=37014&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19519419%26dopt%3DAbstract Authors: Lu Y, Williamson B, Gillespie R Hydrophobic interaction chromatography (HIC) is a classic purification tool applied in protein and antibody, laboratory and industrial production process. It has been mainly used for the removal of both product-related impurities such as aggregates, as well as process contaminants such as host cell proteins. This review will focus on the recent development of HIC in its applications in the industrial purification processes. The process economy and requirements of high product purity and quality have driven much of the recent advancement in HIC chromatography in terms of increased throughput and enhanced selectivity or resolution. Meanwhile, high throughput screening (HTS), design of experiments (DoE) and platform approach for process development... Current Pharmaceutical Biotechnology journals http://www.medworm.com/rss/comments.php?id=2549018 Sun, 31 May 2009 23:00:00 +0100 2549018 http://www.medworm.com/index.php?rid=2549017&cid=s_37014_70_f&fid=37014&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19519420%26dopt%3DAbstract Authors: Gagnon P Charged-hydrophobic mixed mode chromatography methods have been applied to antibody purification for decades and have focused more recently on the specific task of aggregate removal. They exploit various combinations of alkyl and aromatic hydrophobic groups with positively and/or negatively charged residues. Charge and hydrophobicity remain relatively constant as function of pH for some ligands; one or both vary for others. All of these compound selectivities and their associated elution strategies are intended to achieve purification of native IgG through preferential retention of aggregates. This review focuses on the two members of this family that have shown the most promise for aggregate removal: MEP HyperCel() and Capto() adhere. It defines how they work, how th... Current Pharmaceutical Biotechnology journals http://www.medworm.com/rss/comments.php?id=2549017 Sun, 31 May 2009 23:00:00 +0100 2549017 http://www.medworm.com/index.php?rid=2549016&cid=s_37014_70_f&fid=37014&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19519421%26dopt%3DAbstract Authors: Gagnon P, Beam K Hydroxyapatite (HA) has proven in recent years to be one of the most versatile and powerful methods for removing aggregates from antibody preparations. It is effective with IgA, IgG and IgM, and it reduces aggregate levels from above 60% to less than 0.1%. Three basic elution strategies have evolved, one that removes aggregates from a modest proportion of clones, another from the majority, and one that appears to be universally effective. Each has distinct development and process ramifications. This review defines what HA is, how it interacts with various classes of biomolecules, how those interactions are controlled by different elution strategies, and how to determine which approach may be most effective for a particular antibody. Consideration is also given... Current Pharmaceutical Biotechnology journals http://www.medworm.com/rss/comments.php?id=2549016 Sun, 31 May 2009 23:00:00 +0100 2549016 http://www.medworm.com/index.php?rid=2549015&cid=s_37014_70_f&fid=37014&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19519422%26dopt%3DAbstract Authors: Seefeldt MB, Rosendahl MS, Cleland JL, Hesterberg LK Non-denaturing pressures of around 2000 bar are effective for eliminating and refolding protein aggregates and may be applicable in various phases of protein manufacturing to decrease aggregate levels in products and improve process yields. Lower aggregate levels can result in reduced immunogenicity of proteins and enable the correct refolding of proteins that might not be recovered with traditional techniques. High pressure treatment can also be used to conduct selective PEGylation and protease cleavage reactions while minimizing protein aggregation. High pressure processes have been used in the food industry for over 50 years and large scale (300 L) systems are commercially available, enabling production of proteins on the... Current Pharmaceutical Biotechnology journals http://www.medworm.com/rss/comments.php?id=2549015 Sun, 31 May 2009 23:00:00 +0100 2549015 http://www.medworm.com/index.php?rid=2549014&cid=s_37014_70_f&fid=37014&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19519423%26dopt%3DAbstract Authors: Arakawa T, Kita Y, Sato H, Ejima D A number of approaches are available in minimizing aggregation of the final protein products. This chapter describes one such approach, i.e., an attempt to avoid stressful conditions that may eventually lead to protein aggregation. Affinity chromatography uses specific interaction between protein to be purified and ligand attached to the column. Due to high affinity, dissociation of such interaction and hence elution often require harsh solvent conditions. Ion exchange and hydrophobic interaction chromatography also pose certain stressful conditions on proteins. Here we describe development of mild elution buffer using arginine. This chapter covers Protein-A, dye, Protein-A mimetic and antigen affinity chromatography. PMID: 19519423 [PubM... Current Pharmaceutical Biotechnology journals http://www.medworm.com/rss/comments.php?id=2549014 Sun, 31 May 2009 23:00:00 +0100 2549014 http://www.medworm.com/index.php?rid=2549013&cid=s_37014_70_f&fid=37014&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19519424%26dopt%3DAbstract Authors: Arakawa T, Kita Y, Ejima D Ion exchange chromatography (IEC) poses stresses on proteins in both binding and elution steps. Proteins often bind to the column with high affinity, resulting in concentration of the protein upon binding. Elution often requires high salt concentration, leading to high protein concentration with high salt concentration. Although hydrophobic interaction chromatography (HIC) involves weak interaction, salting-out salts are used for binding. These conditions may cause protein aggregation. This short article describes an approach to reduce such aggregation in IEC and HIC. This was achieved by adding small amount of salt or arginine in the loading sample or elution solvent, resulting in elution of proteins with less aggregation or higher recovery. PMI... Current Pharmaceutical Biotechnology journals http://www.medworm.com/rss/comments.php?id=2549013 Sun, 31 May 2009 23:00:00 +0100 2549013 http://www.medworm.com/index.php?rid=2472434&cid=s_37014_70_f&fid=37014&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19355936%26dopt%3DAbstract Authors: Armato U PMID: 19355936 [PubMed - in process] (Source: Current Pharmaceutical Biotechnology) Current Pharmaceutical Biotechnology journals http://www.medworm.com/rss/comments.php?id=2472434 Wed, 01 Apr 2009 04:00:00 +0100 2472434 http://www.medworm.com/index.php?rid=2472399&cid=s_37014_70_f&fid=37014&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19355937%26dopt%3DAbstract Authors: Brennan SC, Conigrave AD The extracellular calcium-sensing receptor (CaR) is a class III G-protein coupled receptor that coordinates cellular responses to changes in extracellular free Ca(2+) or amino acid concentrations as well as ionic strength and pH. It regulates signalling cascades via recruiting and controlling the activities of various heterotrimeric G-proteins, including G(q/11), G(i/0), and G(12/13), even G(s) in some "unusual" circumstances, thereby inducing changes in the metabolism of membrane lipids, the phosphorylation state of protein kinases and their targets, the activation state of monomeric G-proteins and the levels of intracellular second messengers including cAMP, Ca(2+) ions, fatty acids and other small molecules. According to its site(s) of expression an... Current Pharmaceutical Biotechnology journals http://www.medworm.com/rss/comments.php?id=2472399 Wed, 01 Apr 2009 04:00:00 +0100 2472399 http://www.medworm.com/index.php?rid=2472369&cid=s_37014_70_f&fid=37014&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19355938%26dopt%3DAbstract Authors: Molostvov G, Bland R, Zehnder D The calcium-sensing receptor (CaSR), which is involved in systemic calcium homeostasis, has also been found to be functionally expressed on cells of the vascular wall. Its activation on perivascular nerves and endothelial cells has been shown to regulate arterial tone, peripheral vascular resistance and possibly local tissue perfusion. The expression of the CaSR on immune cells involved in vascular inflammation, such as macrophages, and its increased expression in inflammation indicates the central role extracellular calcium plays in vascular inflammation and repair. Further detailed analysis will clarify the role the vascular CaSR plays as a therapeutic target for complex disease conditions such as hypertension, tissue hypoperfusion, atheroscle... Current Pharmaceutical Biotechnology journals http://www.medworm.com/rss/comments.php?id=2472369 Wed, 01 Apr 2009 04:00:00 +0100 2472369 http://www.medworm.com/index.php?rid=2472347&cid=s_37014_70_f&fid=37014&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19355939%26dopt%3DAbstract We present the evidence for a non-redundant role for CaR in skeletal mineralization, including our experience in patients with activating CaR mutations. Additionally, we review emerging research on the importance of the CaR to the regulation of serum calcium homeostasis independent of PTH, the role of the CaR in the hematopoietic stem cell niche with implications for bone marrow transplant, and early evidence that implies a role for the CaR as a factor in skeletal metastasis from breast and prostate cancer. We conclude with a discussion of drugs that target the CaR directly either as agonists (calcimimetics) or antagonists (calcilytics), and the consequences for bone physiology and pathology. PMID: 19355939 [PubMed - in process] (Source: Current Pharmaceutical Biotechnology) Current Pharmaceutical Biotechnology journals http://www.medworm.com/rss/comments.php?id=2472347 Wed, 01 Apr 2009 04:00:00 +0100 2472347 http://www.medworm.com/index.php?rid=2472307&cid=s_37014_70_f&fid=37014&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19355940%26dopt%3DAbstract Authors: Vezzoli G, Soldati L, Gambaro G Calcium-sensing receptor (CaSR), a member of family C of the G protein-coupled receptors, is expressed most abundantly in the parathyroid glands and kidney. It plays key role in these two organs because it senses changes in extracellular calcium and regulates PTH secretion and calcium reabsorption to suit the extracellular calcium concentration. In kidney, CaSR is expressed in all nephron segments. It has an inhibitory effect on the reabsorption of calcium, potassium, sodium and water, depending on the particular function of the different tubular tracts. Among its inhibitory effects, CaSR modulates the signaling pathways used by the tubulocytes to activate electrolyte or water reabsorption. The only site where there is no such inhibitory effect ... Current Pharmaceutical Biotechnology journals http://www.medworm.com/rss/comments.php?id=2472307 Wed, 01 Apr 2009 04:00:00 +0100 2472307 http://www.medworm.com/index.php?rid=2472290&cid=s_37014_70_f&fid=37014&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19355941%26dopt%3DAbstract Authors: Whitfield JF Dietary Ca(2+) reduces colon cell proliferation and carcinogenesis, but it becomes ineffective or even tumor-promoting during carcinogenesis. It appears that Ca(2+) and the colon cell CaSR together brake the massive cell production in normal colon crypts. The rapid proliferation of the transit-amplifying (TA) progeny of the colon stem cells at the bases of the crypts is driven by the "Wnt" signaling mechanism that stimulates proliferogenic genes and prevents apoptogenesis. It appears that TA cell cycling stops and terminal differentiation starts when the cells reach a higher level in the crypt where there is enough external Ca(2+) to stimulate the expression of CaSRs, the signals from which stimulate the expression of E-cadherin. At this point the APC (adenomatous... Current Pharmaceutical Biotechnology journals http://www.medworm.com/rss/comments.php?id=2472290 Wed, 01 Apr 2009 04:00:00 +0100 2472290 http://www.medworm.com/index.php?rid=2472261&cid=s_37014_70_f&fid=37014&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19355942%26dopt%3DAbstract Authors: Chiarini A, Dal Pra I, Marconi M, Chakravarthy B, Whitfield JF, Armato U Although the calcium-sensing receptor (CaSR) is expressed by all types of nerve cells in widespread areas of the human central nervous system (CNS), so far its roles in brain pathophysiology remain largely unknown. Here, we review the available evidence concerning the stages of development of sporadic late-onset Alzheimer's disease (LOAD) and the roles therein played by CaSR signaling. As the brain ages, its ability to dispose of dangerous synapse-targeting soluble amyloid beta-(1-42) (sAbeta42) oligomers released from normal neuronal activity declines. As their levels slowly rise, these oligomers increasingly target and eliminate synapses and prevent synapse formation, thereby eroding the foundations of ... Current Pharmaceutical Biotechnology journals http://www.medworm.com/rss/comments.php?id=2472261 Wed, 01 Apr 2009 04:00:00 +0100 2472261 http://www.medworm.com/index.php?rid=2472232&cid=s_37014_70_f&fid=37014&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19355943%26dopt%3DAbstract Authors: Ruhil S, Kumar V, Rathee P In recent years, human umbilical cord blood (HUCB) has emerged as an attractive tool for cell-based therapy. Although at present the clinical application of human umbilical cord blood is limited to the fields of hematology and oncology, a rising number of studies show potential for further application in the treatment of non-hematopoietic diseases. Stem cells (SC) from umbilical cord blood (UCB) are now a new reliable alternative to treat different blood diseases, if the samples are frozen at the moment of birth. This procedure is an easy and safe way to preserve genetic materials for future therapeutic uses. It can be used as alternative to bone marrow. Human umbilical cord blood, with its real abundance, simple collection procedure and no serious e... Current Pharmaceutical Biotechnology journals http://www.medworm.com/rss/comments.php?id=2472232 Wed, 01 Apr 2009 04:00:00 +0100 2472232 http://www.medworm.com/index.php?rid=2472204&cid=s_37014_70_f&fid=37014&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19355944%26dopt%3DAbstract Authors: Basak GW, Srivastava AS, Malhotra R, Carrier E "Niche" is defined as a specialized regulatory microenvironment, consisting of components which control the fate specification of stem and progenitor cells, as well as maintaining their development by supplying the requisite factors. Bone marrow (BM) niche has a well-organized architecture and is composed of osteoblasts, osteoclasts, bone marrow endothelial cells, stromal cells, adipocytes and extracellular matrix proteins (ECM). These elements play an essential role in the survival, growth and differentiation of diverse lineages of blood cells, but also provide optimal growth environment for multiple hematological malignancies including multiple myeloma (MM). MM is a neoplastic plasma cell disorder which not only resides in BM bu... Current Pharmaceutical Biotechnology journals http://www.medworm.com/rss/comments.php?id=2472204 Wed, 01 Apr 2009 04:00:00 +0100 2472204 http://www.medworm.com/index.php?rid=2184285&cid=s_37014_70_f&fid=37014&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19199960%26dopt%3DAbstract Authors: Miyamoto N, Namiki K, Tokuhara N, Uesugi M, Takahashi E, Kuromitsu J, Kasuya Y Using gene knockout mice of particular genes is one of the most effective methods in conducting successful study on the mode of action of target gene products in targeted organs. So called the knockout technology is now a powerful tool that can lead us to find clear understanding on difficult questions such as the effects of full antagonist against target molecules. Cacna1b (alpha(1B)) gene knockout mouse was generated to study mechanisms of N-type calcium (Ca(2+)) channel. The model was able to overcome physiological obstacles in studies of N-type Ca(2+) channel selective blockers, such as unspecific binding to structurally similar molecules, and failed distribution to targeted organs. In the case ... Current Pharmaceutical Biotechnology journals http://www.medworm.com/rss/comments.php?id=2184285 Sun, 01 Feb 2009 05:00:00 +0100 2184285 http://www.medworm.com/index.php?rid=2174101&cid=s_37014_70_f&fid=37014&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19199945%26dopt%3DAbstract Authors: Banerjee D PMID: 19199945 [PubMed - in process] (Source: Current Pharmaceutical Biotechnology) Current Pharmaceutical Biotechnology journals http://www.medworm.com/rss/comments.php?id=2174101 Sun, 01 Feb 2009 05:00:00 +0100 2174101 http://www.medworm.com/index.php?rid=2174100&cid=s_37014_70_f&fid=37014&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19199946%26dopt%3DAbstract Authors: Rameshwar P This review focuses on the properties of different breast cancer cell subsets, including cancer stem cells (CSCs) and cancer progenitors. The premise is that an understanding of self-renewal, the effects of aging microenvironment on the behavior of cancer cell subsets will map the path of development from CSCs to progenitors. The basic characterization of different cancer cell subsets will lead to their signatures and open the field to novel methods of prognosis and diagnosis. The identification of cancer progenitors would allow scientists to modify the cells genetically for de-differention to CSCs. This will benefit the field to understand the method by which CSCs are developed. The review discusses a reductionist approach for identifying the CSCs and other subset... Current Pharmaceutical Biotechnology journals http://www.medworm.com/rss/comments.php?id=2174100 Sun, 01 Feb 2009 05:00:00 +0100 2174100 http://www.medworm.com/index.php?rid=2174099&cid=s_37014_70_f&fid=37014&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19199947%26dopt%3DAbstract Authors: Purow B Notch was first recognized as an important developmental pathway in Drosophila in the first half of the 20(th) century. Many decades later, this pathway has been found to play central roles in humans in stem cell maintenance, cell fate decisions, and in cancer as well. Notch family members are being revealed as oncogenes in an ever-increasing number of cancers. Though significant progress has been made in dissecting the complex workings of this signaling pathway, there are very limited options available for Notch inhibitors. However, the pioneering class of Notch inhibitors is already in clinical trials for two cancer types. This review will address the current state-of-the-art, agents in the pipeline, and potential strategies for future Notch inhibitors. Successful de... Current Pharmaceutical Biotechnology journals http://www.medworm.com/rss/comments.php?id=2174099 Sun, 01 Feb 2009 05:00:00 +0100 2174099 http://www.medworm.com/index.php?rid=2174098&cid=s_37014_70_f&fid=37014&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19199948%26dopt%3DAbstract Authors: Humeniuk R, Mishra PJ, Bertino JR, Banerjee D Recent advances in cancer research showed that changes of the cell "epigenome" contribute significantly to the development and progression of cancer. Similar to genetic alterations, epigenetic modifications can be transmitted to the next generation and used to turn off and/or on certain genes or pathways that may confer survival benefit to a malignant cell. However, epigenetic changes are readily reversible raising the possibility of "epigenetic therapy". A potential problem in this therapeutic approach is the lack of specificity, as epigenetic modifications are used by both normal and cancer cells to regulate expression of various genes. Ongoing studies to identify genes that are differentially expressed in cancer cells vs. normal... Current Pharmaceutical Biotechnology journals http://www.medworm.com/rss/comments.php?id=2174098 Sun, 01 Feb 2009 05:00:00 +0100 2174098 http://www.medworm.com/index.php?rid=2174097&cid=s_37014_70_f&fid=37014&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19199949%26dopt%3DAbstract Authors: Chaudhuri D, Suriano R, Mittelman A, Tiwari RK The concept of cancer immunotherapy provides a fresh perspective as it is not associated with many of the drawbacks of conventional therapies such as chemotherapy, radiotherapy and surgery. When fully activated the immune system has immense potential as is evident from mis-matched transplanted organs undergoing rapid immunological attack and rejection. However, the development of immune strategies for cancer therapy has been associated with challenges of their own. Early attempts at cancer vaccination were carried out in an empirical manner that did not always lead to reproducibility. This led to a search of tumor associated antigens with the belief that specific targeting of these antigens would lead to successful tumor eliminati... Current Pharmaceutical Biotechnology journals http://www.medworm.com/rss/comments.php?id=2174097 Sun, 01 Feb 2009 05:00:00 +0100 2174097 http://www.medworm.com/index.php?rid=2174096&cid=s_37014_70_f&fid=37014&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19199950%26dopt%3DAbstract Authors: Anton K, Glod J Increasing evidence shows that the interaction between neoplastic cells and the surrounding stroma is a critical factor in solid tumor growth. The tumor stroma is made up of diverse cellular populations including macrophages, lymphocytes, vascular cells, and carcinoma-associated fibroblasts. The complex interactions between the stroma and neoplastic cells are largely unexplored. Initial therapies aimed at disrupting angiogenesis within the tumor microenvironment have met with success in a number of tumor types. An improved understanding of stromal signaling pathways is likely to identify additional novel therapeutic targets. PMID: 19199950 [PubMed - in process] (Source: Current Pharmaceutical Biotechnology) Current Pharmaceutical Biotechnology journals http://www.medworm.com/rss/comments.php?id=2174096 Sun, 01 Feb 2009 05:00:00 +0100 2174096 http://www.medworm.com/index.php?rid=2174095&cid=s_37014_70_f&fid=37014&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19199951%26dopt%3DAbstract Authors: Bansal N, Banerjee D Cancer Stem cells (CSC) are defined as a population of cells found within a tumor that have characteristics similar to normal stem cells. Like normal stem cells they have the potential to self renew and differentiate. The cellular origin of these cancer stem cells - whether they originate from stem cells that have lost the ability to regulate proliferation, or they arise from more differentiated population of progenitor cells that have acquired abilities to self-renew is still unclear. Investigators have reported isolation of cancer stem cells or tumor initiating cells using techniques developed for isolating hematopoietic stem cells and assays that identify a small subset of tumor initiating cells. The TICs are thought to play an important role in tumor d... Current Pharmaceutical Biotechnology journals http://www.medworm.com/rss/comments.php?id=2174095 Sun, 01 Feb 2009 05:00:00 +0100 2174095 http://www.medworm.com/index.php?rid=2174094&cid=s_37014_70_f&fid=37014&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19199952%26dopt%3DAbstract Authors: Abe K, Kimura M, Yamamura K PMID: 19199952 [PubMed - in process] (Source: Current Pharmaceutical Biotechnology) Current Pharmaceutical Biotechnology journals http://www.medworm.com/rss/comments.php?id=2174094 Sun, 01 Feb 2009 05:00:00 +0100 2174094 http://www.medworm.com/index.php?rid=2174093&cid=s_37014_70_f&fid=37014&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19199953%26dopt%3DAbstract Authors: Soewarto D, Klaften M, Rubio-Aliaga I Aim of this review is to demonstrate the relevance of animal models created by ENU mutagenesis for the pharmaceutical community to understand diseases and the modulation of disease status by pharmaceutical compounds. We give an overview of what ENU mutagenesis in mice implies and introduce the main research centers running ENU mutagenesis projects. The different strategies of ENU mutagenesis screens are explained as well as the latest advances in mapping and mutation detection strategies, which until recently have been the main limiting step in forward genetics/phenotype-driven approaches. ENU mutagenesis in mice has shown its power by providing animal models for human monogenic diseases. Moreover, the development of modifier and sensitize... Current Pharmaceutical Biotechnology journals http://www.medworm.com/rss/comments.php?id=2174093 Sun, 01 Feb 2009 05:00:00 +0100 2174093 http://www.medworm.com/index.php?rid=2174092&cid=s_37014_70_f&fid=37014&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19199954%26dopt%3DAbstract Authors: Mashimo T, Serikawa T The laboratory rat is obviously an important model for physiology, pathology, pharmacology, toxicology, and transplantation experiments. The value for pharmacological research is immense since virtually every drug approved for human treatment passes through the body of laboratory rats. Hundreds of unique rat models have been developed to mimic pathological and physiological human clinical conditions, especially in the case of complex diseases. Many of the model rats are deposited into rat resource centers, from which researchers can use and share animals and rat related resources in biomedical research. Recent progressing technologies for genetically engineered rats, such as traditional transgenesis, chemical ENU mutagenesis, and transposon insertional mu... Current Pharmaceutical Biotechnology journals http://www.medworm.com/rss/comments.php?id=2174092 Sun, 01 Feb 2009 05:00:00 +0100 2174092 http://www.medworm.com/index.php?rid=2174091&cid=s_37014_70_f&fid=37014&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19199955%26dopt%3DAbstract Authors: Araki M, Araki K, Yamamura K While the human genome project has been completed, analysis of functions of each gene is still underway. Knockout and knock down of gene products offer useful tools to understand functions of a single gene in vivo. Production of knockout mice using homologous recombination in embryonic stem (ES) cells is a powerful and established strategy. However, it is laborious, time-consuming and expensive if expanding large scale. In mice, the gene trap is an alternative strategy to disrupt gene functions by random disruption of gene. The functions of a gene in vivo can be analyzed by production of mice from trapped ES clones. Large-scale gene trap projects have been started in some research centers of the world, and the International Gene Trap Consortium (IG... Current Pharmaceutical Biotechnology journals http://www.medworm.com/rss/comments.php?id=2174091 Sun, 01 Feb 2009 05:00:00 +0100 2174091 http://www.medworm.com/index.php?rid=2174090&cid=s_37014_70_f&fid=37014&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19199956%26dopt%3DAbstract Authors: Matsushima Y Personalized medicine offers a custom-made treatment for each patient directed by information of individual's genetic variation. Despite plenty of information about human single nucleotide polymorphisms (SNPs) and gene expression profile, predicting functions of genetic variations in humans is still a difficult task. Genetic analysis using experimental animals is possible to provide information about the functions of genetic polymorphisms over experimental invention in humans. In particular, inbred strains established from wild mice are valuable resources for analyzing functions of genetic polymorphisms. In this article, first I describe history of inbred strains derived from Japanese wild mice, Mus musuclus molossinus. Next, I discuss a mouse model for hyperlipid... Current Pharmaceutical Biotechnology journals http://www.medworm.com/rss/comments.php?id=2174090 Sun, 01 Feb 2009 05:00:00 +0100 2174090 http://www.medworm.com/index.php?rid=2174089&cid=s_37014_70_f&fid=37014&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19199957%26dopt%3DAbstract Authors: Fuchs H, Gailus-Durner V, Adler T, Pimentel JA, Becker L, Bolle I, Brielmeier M, Calzada-Wack J, Dalke C, Ehrhardt N, Fasnacht N, Ferwagner B, Frischmann U, Hans W, Hölter SM, Hölzlwimmer G, Horsch M, Javaheri A, Kallnik M, Kling E, Lengger C, Maier H, Moßbrugger I, Mörth C, Naton B, Nöth U, Pasche B, Prehn C, Przemeck G, Puk O, Racz I, Rathkolb B, Rozman J, Schäble K, Schreiner R, Schrewe A, Sina C, Steinkamp R, Thiele F, Willershäuser M, Zeh R, Adamski J, Busch DH, Beckers J, Behrendt H, Daniel H, Esposito I, Favor J, Graw J, Heldmaier G, Höfler H, Ivandic B, Katus H, Klingenspor M, Klopstock T, Lengeling A, Mempel M, Müller W, Neschen S, Ollert M, Quintanilla-Martinez L, Rosenstiel P, Schmidt J, Schreiber S, Schughart K, Schulz H, Wo... Current Pharmaceutical Biotechnology journals http://www.medworm.com/rss/comments.php?id=2174089 Sun, 01 Feb 2009 05:00:00 +0100 2174089 http://www.medworm.com/index.php?rid=2174088&cid=s_37014_70_f&fid=37014&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19199958%26dopt%3DAbstract Authors: Ohtsuka M, Kimura M, Tanaka M, Inoko H Genetically modified animals have been used as models in broad range of studies including pharmaceutical biology. Designing and construction of transgene constructs are the first indispensable task in generating model animals. In addition to the classical restriction enzyme-based method, still holds some advantages in generating precise constructs, site-specific recombinase-based and homologous recombination-based DNA engineering strategies (e.g. Gateway and Red/ET recombineering, respectively) have been developed and widely used for vector construction or BAC modification. In this review, the three construction methods are described and their applications are discussed such as tandem assemblies of multiple components and modification of ... Current Pharmaceutical Biotechnology journals http://www.medworm.com/rss/comments.php?id=2174088 Sun, 01 Feb 2009 05:00:00 +0100 2174088 http://www.medworm.com/index.php?rid=2174087&cid=s_37014_70_f&fid=37014&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19199959%26dopt%3DAbstract Authors: Abe K, Yu P One of the upcoming next quests in the field of genetics might be molecular dissection of the genetic and environmental components of human complex diseases. In humans, however, there are certain experimental limitations for identification of a single component of the complex interactions by genetic analyses. Experimental animals offer simplified models for genetic and environmental interactions in human complex diseases. In particular, mice are the best mammalian models because of a long history and ample experience for genetic analyses. Forward genetics, which includes genetic screen and subsequent positional cloning of the causative genes, is a powerful strategy to dissect a complex phenomenon without preliminarily molecular knowledge of the process. In this rev... Current Pharmaceutical Biotechnology journals http://www.medworm.com/rss/comments.php?id=2174087 Sun, 01 Feb 2009 05:00:00 +0100 2174087 http://www.medworm.com/index.php?rid=2174086&cid=s_37014_70_f&fid=37014&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19199960%26dopt%3DAbstract Authors: Miyamoto N, Namiki K, Tokuhara N, Uesugi M, Takahashi E, Kuromitsu J, Kasuya Y Using gene knockout mice of particular genes is one of the most effective methods in conducting successful study on the mode of action of target gene products in targeted organs. So called the knockout technology is now a powerful tool that can lead us to find clear understanding on difficult questions such as the effects of full antagonist against target molecules. Cacna1b (alpha(iB)) gene knockout mouse was generated to study mechanisms of N-type calcium (Ca(2+)) channel. The model was able to overcome physiological obstacles in studies of N-type Ca(2+) channel selective blockers, such as unspecific binding to structurally similar molecules, and failed distribution to targeted organs. In the case ... Current Pharmaceutical Biotechnology journals http://www.medworm.com/rss/comments.php?id=2174086 Sun, 01 Feb 2009 05:00:00 +0100 2174086 http://www.medworm.com/index.php?rid=2116765&cid=s_37014_70_f&fid=37014&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19149586%26dopt%3DAbstract Authors: de Freire Bastos MD PMID: 19149586 [PubMed - as supplied by publisher] (Source: Current Pharmaceutical Biotechnology) Current Pharmaceutical Biotechnology journals http://www.medworm.com/rss/comments.php?id=2116765 Thu, 01 Jan 2009 05:00:00 +0100 2116765 http://www.medworm.com/index.php?rid=2116764&cid=s_37014_70_f&fid=37014&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19149587%26dopt%3DAbstract Authors: Bierbaum G, Sahl HG Lantibiotics are gene-encoded peptides that contain intramolecular ring structures, introduced through the thioether containing lanthionine and methyllanthionine residues. The overwhelming majority of the lantibiotics shows antibacterial activity. Some lantibiotics, e.g. nisin, are characterized by a dual mode of action. These peptides form a complex with the ultimate cell wall precursor lipid II, thereby inhibiting cell wall biosynthesis. The complexes then aggregate, incorporate further peptides and form a pore in the bacterial membrane. Recent results show that complexing of lipid II is widespread among lantibiotics; however, pore formation depends on the overall length of the peptide and the lipid composition of the test strain membrane. In the two-comp... Current Pharmaceutical Biotechnology journals http://www.medworm.com/rss/comments.php?id=2116764 Thu, 01 Jan 2009 05:00:00 +0100 2116764 http://www.medworm.com/index.php?rid=2116763&cid=s_37014_70_f&fid=37014&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19149588%26dopt%3DAbstract Authors: Nissen-Meyer J, Rogne P, Oppegârd C, Haugen HS, Kristiansen PE This review focuses on the structure and mode-of-action of non-lanthionine-containing peptide bacteriocins produced by Gram-positive bacteria. These bacteriocins may be divided into four groups: (i) the anti-listerial one-peptide pediocin-like bacteriocins that have very similar amino acid sequences, (ii) the two-peptide bacteriocins that consist of two different peptides, (iii) the cyclic bacteriocins, and (iv) the linear non-pediocin-like one-peptide bacteriocins. These bacteriocins are largely cationic, contain 20 to 70 residues, and kill cells through membrane-permeabilization. The pediocin-like bacteriocins are the ones that are best characterized. Upon contact with target membranes, their cationic N-term... Current Pharmaceutical Biotechnology journals http://www.medworm.com/rss/comments.php?id=2116763 Thu, 01 Jan 2009 05:00:00 +0100 2116763 http://www.medworm.com/index.php?rid=2116762&cid=s_37014_70_f&fid=37014&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19149589%26dopt%3DAbstract Authors: Bastos MC, Ceotto H, Coelho ML, Nascimento JS Bacteriocins are bacterial antimicrobial peptides with bactericidal activity against other bacteria. Staphylococcins are bacteriocins produced by staphylococci, which are Gram-positive bacteria with medical and veterinary importance. Most bacteriocins produced by staphylococci are either lantibiotics (e.g., Pep5, epidermin, epilancin K7, epicidin 280, staphylococcin C55/BacR1, and nukacin ISK-1) or class II bacteriocins (e.g., aureocins A70 and 53). Only one staphylococcin belonging to class III, lysostaphin, has been described so far. Production of staphylococcins is a self-protection mechanism that helps staphylococci to survive in their natural habitats. However, since these substances generally have a broad spectrum of activity... Current Pharmaceutical Biotechnology journals http://www.medworm.com/rss/comments.php?id=2116762 Thu, 01 Jan 2009 05:00:00 +0100 2116762 http://www.medworm.com/index.php?rid=2116761&cid=s_37014_70_f&fid=37014&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19149590%26dopt%3DAbstract Authors: Diep DB, Mathiesen G, Eijsink VG, Nes IF Lactobacilli are common microorganisms in diverse vegetables and meat products and several of these are also indigenous inhabitants in the gastro-intestinal (GI) tract of humans and animals where they are believed to have health promoting effects on the host. One of the highly appreciated probiotic effects is their ability to inhibit the growth of pathogens by producing antimicrobial peptides, so-called bacteriocins. Production of some bacteriocins has been shown to be strictly regulated through a quorum-sensing based mechanism mediated by a secreted peptide-pheromone (also called induction peptide; IP), a membrane-located sensor (histidine protein kinase; HPK) and a cytoplasmic response regulator (RR). The interaction between an IP and... Current Pharmaceutical Biotechnology journals http://www.medworm.com/rss/comments.php?id=2116761 Thu, 01 Jan 2009 05:00:00 +0100 2116761 http://www.medworm.com/index.php?rid=2116760&cid=s_37014_70_f&fid=37014&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19149591%26dopt%3DAbstract Authors: Lagos R, Tello M, Mercado G, García V, Monasterio O Microcins are a family of low-molecular weight bacteriocins produced and secreted by Gram-negative bacteria. This review is focused on microcin E492, a pore-forming bacteriocin produced by Klebsiella pneumoniae RYC492 that exerts its antibacterial action on related strains. The steps necessary for the production of active microcin E492 involve post-translational modification with a catechol-type siderophore at the C-terminal and proteolytic processing during export to the extracellular space. This bacteriocin has a modular structure, with a toxic domain at the N-terminal and an uptake domain at the C-terminal of the mature protein. The mechanism by which the C-terminal of microcin E492 is recognized by catecholate sidero... Current Pharmaceutical Biotechnology journals http://www.medworm.com/rss/comments.php?id=2116760 Thu, 01 Jan 2009 05:00:00 +0100 2116760 http://www.medworm.com/index.php?rid=2116759&cid=s_37014_70_f&fid=37014&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19149592%26dopt%3DAbstract Authors: Laport MS, Santos OC, Muricy G Sponges (phylum Porifera) are sessile marine filter feeders that have developed efficient defense mechanisms against foreign attackers such as viruses, bacteria, or eukaryotic organisms. Marine sponges are among the richest sources of pharmacologically-active chemicals from marine organisms. It is suggested that (at least) some of the bioactive secondary metabolites isolated from sponges are produced by functional enzyme clusters, which originated from the sponges and their associated microorganisms. More than 5,300 different products are known from sponges and their associated microorganisms, and more than 200 new metabolites from sponges are reported each year. As infectious microorganisms evolve and develop resistance to existing pharmaceutica... Current Pharmaceutical Biotechnology journals http://www.medworm.com/rss/comments.php?id=2116759 Thu, 01 Jan 2009 05:00:00 +0100 2116759 http://www.medworm.com/index.php?rid=2116758&cid=s_37014_70_f&fid=37014&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19149593%26dopt%3DAbstract Authors: Alviano DS, Alviano CS Medicinal plants constitute the base of health care systems in many societies. The recovery of the knowledge and practices associated with these plant resources are part of an important strategy linked to the conservation of biodiversity, discovery of new medicines, and the bettering of the quality of life of poor rural communities. Research in phytosciences, an emerging multidisciplinary science, is almost unlimited, with several aspects to be discussed. Therefore, the focus of the present review is mainly on the antimicrobial and antioxidant properties of bioactive phytocompounds resultant of our research with crude plant extracts and essential oils of medicinal plants belonging to different families, used in various infectious disorders. The results o... Current Pharmaceutical Biotechnology journals http://www.medworm.com/rss/comments.php?id=2116758 Thu, 01 Jan 2009 05:00:00 +0100 2116758 http://www.medworm.com/index.php?rid=2116757&cid=s_37014_70_f&fid=37014&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19149594%26dopt%3DAbstract Authors: Stevenson CL Drug delivery strategies for peptide pharmaceuticals have incorporated a wide range of structure activity relationships, analog generation to impart protease resistance and increased bioavailability, novel formulations, and delivery systems to target optimal therapeutic dosing requirements. Advances in peptide pharmaceuticals have provided products for the treatment of diabetes, obesity, Crohn's disease, osteoporosis, cancer, cardiovascular disease, immunotherapy, acromegaly, enuresis, pain, and antimicrobials. Here we review these marketed peptides and new peptidomimetic therapies currently in clinical trials. PMID: 19149594 [PubMed - as supplied by publisher] (Source: Current Pharmaceutical Biotechnology) Current Pharmaceutical Biotechnology journals http://www.medworm.com/rss/comments.php?id=2116757 Thu, 01 Jan 2009 05:00:00 +0100 2116757 http://www.medworm.com/index.php?rid=2116756&cid=s_37014_70_f&fid=37014&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19149595%26dopt%3DAbstract Authors: Nan G, Yan H, Yang G, Jian Q, Chen C, Li Z Glycan-protein interactions play important biological roles in biological processes. But there is a lack of simple high-throughput methods to elucidate recognition events between carbohydrates and protein. Although, there have been a number of glycan arrays developed in recent years utilizing different strategies and for different purposes, the method presented in this paper, a direct covalent immobilization of sugars to hydroxyl-modified glass surface, can be a very useful general method. Here, two strategies have been developed for the production of carbohydrate microarrays by the underivatized sugars that efficiently immobilized on hydroxyl-functionalized glass surface by formation of glycosidic bond with the hemiacetal group at th... Current Pharmaceutical Biotechnology journals http://www.medworm.com/rss/comments.php?id=2116756 Thu, 01 Jan 2009 05:00:00 +0100 2116756 http://www.medworm.com/index.php?rid=2054044&cid=s_37014_70_f&fid=37014&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19075681%26dopt%3DAbstract Authors: Beck A, Wurch T, Corvaïa N PMID: 19075681 [PubMed - in process] (Source: Current Pharmaceutical Biotechnology) Current Pharmaceutical Biotechnology journals http://www.medworm.com/rss/comments.php?id=2054044 Mon, 01 Dec 2008 05:00:00 +0100 2054044 http://www.medworm.com/index.php?rid=2054043&cid=s_37014_70_f&fid=37014&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19075683%26dopt%3DAbstract Authors: Schneider CK The development of new monoclonal antibodies (mAbs) is a still evolving field in finding new therapeutics. Structurally, mAbs have evolved over the past years by change from fully murine molecules to chimaeric antibodies or even humanized or fully human molecules. Although being "monoclonal" in terms of specificity, mAbs can be heterogeneous with respect to molecular features like microheterogeneity and glycosylation due to their complex manufacturing processes. Small changes in these processes can have considerable consequences on the product and also clinical safety and/or efficacy. Thus, quality, non-clinical and clinical data should not be seen as separate fields, but can impact on each other. For clinical trials of mAbs, non-clinical data from relevant specie... Current Pharmaceutical Biotechnology journals http://www.medworm.com/rss/comments.php?id=2054043 Mon, 01 Dec 2008 05:00:00 +0100 2054043 http://www.medworm.com/index.php?rid=2041332&cid=s_37014_70_f&fid=37014&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19075681%26dopt%3DAbstract Authors: Beck A, Wurch T, Corvaîa N PMID: 19075681 [PubMed - in process] (Source: Current Pharmaceutical Biotechnology) Current Pharmaceutical Biotechnology journals http://www.medworm.com/rss/comments.php?id=2041332 Mon, 01 Dec 2008 05:00:00 +0100 2041332 http://www.medworm.com/index.php?rid=2041331&cid=s_37014_70_f&fid=37014&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19075682%26dopt%3DAbstract Authors: Reichert JM Monoclonal antibodies (mAbs) comprise the majority of protein candidates currently in clinical development because of their versatility as therapeutic agents. While traditionally associated with the biotechnology industry, mAb therapeutics are now being developed and marketed by most major pharmaceutical firms. A total of 21 products are approved in the US, with additional products marketed outside the US, and over 200 mAb candidates are currently undergoing clinical study. Benchmark data for mAb therapeutics, such as clinical development and US Food and Drug Administration approval times, approval success rates, and clinical phase transition probabilities, are critical for strategic planning purposes. Trends in these benchmarks for various types of mAbs, with an e... Current Pharmaceutical Biotechnology journals http://www.medworm.com/rss/comments.php?id=2041331 Mon, 01 Dec 2008 05:00:00 +0100 2041331 http://www.medworm.com/index.php?rid=2041330&cid=s_37014_70_f&fid=37014&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19075683%26dopt%3DAbstract Authors: Schneider CK The development of new monoclonal antibodies (mAbs) is a still evolving field in finding new therapeutics. Structurally, mAbs have evolved over the past years by change from fully murine molecules to chimaeric antibodies or even humanized or fully human molecules. Although being "monoclonal" in terms of specificity, mAbs can be heterogeneous with respect to molecular features like microheterogeneity and glycosylation due to their complex manufacturing processes. Small changes in these processes can have considerable consequences on the product and also clinical safety and/or efficacy. Thus, quality, non-clinical and clinical data should not be seen as separate fields, but can impact on each other. For clinical trials of mAbs, non-clinical data from relevant specie... Current Pharmaceutical Biotechnology journals http://www.medworm.com/rss/comments.php?id=2041330 Mon, 01 Dec 2008 05:00:00 +0100 2041330 http://www.medworm.com/index.php?rid=2041329&cid=s_37014_70_f&fid=37014&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19075684%26dopt%3DAbstract This article gives an overview about the development of human therapeutic antibodies generated by phage display. After an introduction to the method, the focus is on approved antibodies and those currently in clinical trials, 14 of which are described in detail. PMID: 19075684 [PubMed - in process] (Source: Current Pharmaceutical Biotechnology) Current Pharmaceutical Biotechnology journals http://www.medworm.com/rss/comments.php?id=2041329 Mon, 01 Dec 2008 05:00:00 +0100 2041329 http://www.medworm.com/index.php?rid=2041328&cid=s_37014_70_f&fid=37014&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19075685%26dopt%3DAbstract This article provides an overview of the upstream technologies used in the industrial production of therapeutic monoclonal antibodies (mAbs) based on the cultivation of mammalian cells. More specifically, in a first section, after a short discussion of relevant biochemical characteristics of antibodies, we review the cell lines currently employed in commercial production and the methods of constructing and isolating production clones. This is followed with a review of the most current methods of commercial scale production and their associated technologies. Selected references and short discussions pertaining to emerging and relevant technologies have been embedded throughout the text in order to give a sense of the overall direction the field is taking. PMID: 19075685 [PubMed - in pro... Current Pharmaceutical Biotechnology journals http://www.medworm.com/rss/comments.php?id=2041328 Mon, 01 Dec 2008 05:00:00 +0100 2041328 http://www.medworm.com/index.php?rid=2041327&cid=s_37014_70_f&fid=37014&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19075686%26dopt%3DAbstract Authors: Vlasak J, Ionescu R The expanding field of monoclonal antibody-based pharmaceuticals has triggered increased interest in analytical characterization of these large proteins and in understanding of their heterogeneity and degradation pathways. As a result, a large number of enzymatic modifications as well as chemical and physical degradations have been reported in monoclonal antibodies in recent years. Most heterogeneity is related to changes in the surface charge of the antibody, either directly, as a change in the number of charged residues, or indirectly as a chemical or physical alteration that changes surface-charge distribution. This review presents an overview of the sources of charge-related heterogeneity in monoclonal antibodies and the methods used for their detection... Current Pharmaceutical Biotechnology journals http://www.medworm.com/rss/comments.php?id=2041327 Mon, 01 Dec 2008 05:00:00 +0100 2041327 http://www.medworm.com/index.php?rid=2041326&cid=s_37014_70_f&fid=37014&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19075687%26dopt%3DAbstract Authors: Beck A, Wagner-Rousset E, Bussat MC, Lokteff M, Klinguer-Hamour C, Haeuw JF, Goetsch L, Wurch T, Van Dorsselaer A, Corvaîa N Monoclonal antibodies (MAbs) are the fastest growing class of human pharmaceuticals. More than 20 MAbs have been approved and several hundreds are in clinical trials in various therapeutic indications including oncology, inflammatory diseases, organ transplantation, cardiology, viral infection, allergy, and tissue growth and repair. Most of the current therapeutic antibodies are humanized or human Immunoglobulins (IgGs) and are produced as recombinant glycoproteins in eukaryotic cells. Many alternative production systems and improved constructs are also being actively investigated. IgGs glycans represent only an average of around 3 % of the total ma... Current Pharmaceutical Biotechnology journals http://www.medworm.com/rss/comments.php?id=2041326 Mon, 01 Dec 2008 05:00:00 +0100 2041326 http://www.medworm.com/index.php?rid=2041325&cid=s_37014_70_f&fid=37014&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19075688%26dopt%3DAbstract Authors: Wurch T, Lowe P, Caussanel V, Bes C, Beck A, Corvaia N Recent advances in combinatorial protein engineering have made it possible to develop antibody-based and non-Ig protein scaffolds that can potentially substitute for most whole antibody-associated properties. In theory, many different natural human protein backbones are suitable to be used as recombinant templates for engineering : antibody-derived scaffolds, carrier proteins that display a single binding interface, backbones that provide a rigid core structure suitable for grafting loops or protein scaffolds allowing the incorporation of variable loops in a favorable 3D configuration. In practice however, only a few have yielded the necessary properties to be translated into 'druggable Biologicals'. Amongst these properti... Current Pharmaceutical Biotechnology journals http://www.medworm.com/rss/comments.php?id=2041325 Mon, 01 Dec 2008 05:00:00 +0100 2041325 http://www.medworm.com/index.php?rid=2041324&cid=s_37014_70_f&fid=37014&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19075689%26dopt%3DAbstract This study aims to test the predictive power of gene expression data derived from NIH's database dbEST, which collects gene expression results from a large number and variety of DNA array experiments. The motivation of this study is to make comparable experimental studies, which are usually performed only for one or a few tissues or organs, with a wide variety of other tissues. Confirmation of a good predictive power of dbEST would put a number of interesting and partially surprising recent findings, solely based on data mining, on a more solid basis than available so far. The expression of nine genes (eIF4E, DDX6, HAT1, USP28, HSP90(beta, PKM2, PLK1, COX2 and OPN) plus two calibration genes in paired normal and cancer colon tissues of eight individual patients was investigated by quantita... Current Pharmaceutical Biotechnology journals http://www.medworm.com/rss/comments.php?id=2041324 Mon, 01 Dec 2008 05:00:00 +0100 2041324 http://www.medworm.com/index.php?rid=2041323&cid=s_37014_70_f&fid=37014&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19075690%26dopt%3DAbstract Authors: Calayir E, M T, Kratzer BA, Ebner B, Panzenböck U, Stefujl J, Kostner GM Apolipoprotein M (apoM) has been suggested to play a role in reverse cholesterol transport. Here we studied the influence of liver X-receptor (LXR) agonist on the transcriptional regulation of apoM. Studies were performed in murine liver and intestinal mucosal cells in vivo and in human intestinal Caco-2 cells in vitro. The expression of apoM was analyzed by quantitative real time PCR, and compared to well-established LXR target genes. Mice fed with TO901317 for six days showed a downregulation of apoM and apoAI in the liver to 40 % and 60 % respectively and an upregulation of Cyp7A1 to 280 %. In the small intestine, however, apoM and apoAI were upregulated by 30-60 % and ABCA1 by 250-430 %. In Caco-... Current Pharmaceutical Biotechnology journals http://www.medworm.com/rss/comments.php?id=2041323 Mon, 01 Dec 2008 05:00:00 +0100 2041323 http://www.medworm.com/index.php?rid=1884066&cid=s_37014_70_f&fid=37014&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18855685%26dopt%3DAbstract Authors: Anisimov SV PMID: 18855685 [PubMed - in process] (Source: Current Pharmaceutical Biotechnology) Current Pharmaceutical Biotechnology journals http://www.medworm.com/rss/comments.php?id=1884066 Wed, 01 Oct 2008 04:00:00 +0100 1884066 http://www.medworm.com/index.php?rid=1880766&cid=s_37014_70_f&fid=37014&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18855685%26dopt%3DAbstract Authors: Anisimov SV PMID: 18855685 [PubMed - in process] (Source: Current Pharmaceutical Biotechnology) Current Pharmaceutical Biotechnology journals http://www.medworm.com/rss/comments.php?id=1880766 Wed, 01 Oct 2008 04:00:00 +0100 1880766 http://www.medworm.com/index.php?rid=1880765&cid=s_37014_70_f&fid=37014&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18855686%26dopt%3DAbstract Authors: Anisimov SV A number of molecular methods of gene expression analysis can approach genomic level. Among those, Serial Analysis of Gene Expression (SAGE) stands out. Unlike many other techniques, SAGE allows both qualitative and quantitative analysis of previously unknown transcripts. Over the course of the last 13 years, SAGE has became a recognized tool of large-scale gene expression profiling, being used extensively in human, animal, yeast and plant studies of various nature. A number of important adaptations was introduced both to the protocol of SAGE library construction and to the analytical algorithm employed. Moreover, some variations of the original protocol (MAGE, SADE, microSAGE, miniSAGE, longSAGE, superSAGE, deepSAGE, etc.) were derived to improve the utility of SA... Current Pharmaceutical Biotechnology journals http://www.medworm.com/rss/comments.php?id=1880765 Wed, 01 Oct 2008 04:00:00 +0100 1880765 http://www.medworm.com/index.php?rid=1880764&cid=s_37014_70_f&fid=37014&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18855687%26dopt%3DAbstract Authors: Datson NA Since Serial Analysis of Gene Expression (SAGE) was introduced more than a decade ago, it has been widely applied to characterise gene expression profiles in various tissues, cell types and cell lines of diverse origin including human, mouse, rat, yeast, plant and parasites. Throughout the past years many modifications to the original SAGE protocol have been developed, which address several aspects of SAGE, including an increase in sequencing efficiency (deepSAGE), improved tag-to-transcript mapping of SAGE tags (LongSAGE) and a reduction of the amount of required input RNA (microSAGE). Furthermore, the applications of SAGE have expanded from exclusively transcriptome analysis to now also include genome analysis, identifying genome signature tags that pinpoint transc... Current Pharmaceutical Biotechnology journals http://www.medworm.com/rss/comments.php?id=1880764 Wed, 01 Oct 2008 04:00:00 +0100 1880764 http://www.medworm.com/index.php?rid=1880763&cid=s_37014_70_f&fid=37014&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18855688%26dopt%3DAbstract Authors: Wang SM The multiple levels of post-transcriptional processing and million-fold differences in expression levels make fully decoding the transcriptome in any given species extremely challenging. This review addresses the influence of sequenced length on transcriptome decoding under current DNA sequencing capabilities. Comparison of full-length cDNA, EST, 14-base SAGE, 21-LongSAGE, 26-SuperSAGE, and other variations shows that the sequenced length has been a key factor in determining the sensitivity and specificity for mRNA detection. PMID: 18855688 [PubMed - in process] (Source: Current Pharmaceutical Biotechnology) Current Pharmaceutical Biotechnology journals http://www.medworm.com/rss/comments.php?id=1880763 Wed, 01 Oct 2008 04:00:00 +0100 1880763 http://www.medworm.com/index.php?rid=1880762&cid=s_37014_70_f&fid=37014&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18855689%26dopt%3DAbstract Authors: Matsumura H, Krüger DH, Kahl G, Terauchi R SuperSAGE is a variant of SAGE (Serial Analysis of Gene Expression) technology, which allows making transcript profiling by 26-bp tags extracted from cDNA employing the typeIII restriction enzyme EcoP15I. Its tag length is the longest among all the versions of SAGE, and is advantageous in tag-to-gene annotation, thereby allowing the technique to applicable to any eukaryotic life organisms. For model organisms with genome or cDNA sequences available, genes corresponding to 26-bp tags are uniquely defined by simple BLAST search. For non-model organisms without these sequence information, the 26-bp tag sequence is directly applicable to design PCR primer for amplifying cDNA of corresponding genes by 3'- or 5'-RACE. Furthermore, Supe... Current Pharmaceutical Biotechnology journals http://www.medworm.com/rss/comments.php?id=1880762 Wed, 01 Oct 2008 04:00:00 +0100 1880762 http://www.medworm.com/index.php?rid=1880761&cid=s_37014_70_f&fid=37014&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18855690%26dopt%3DAbstract Authors: Yamashita T, Honda M, Kaneko S It is now widely believed that tumors originate from normal cells as a result of accumulated genetic/epigenetic changes. These alterations affect the signaling pathways at transcriptional and post-transcriptional level that drive cells into uncontrolled cell division, growth, and migration. Recent advancement of molecular technologies have yielded comprehensive gene expression profiling techniques that have successfully provided candidate diagnostic and prognostic markers in human cancers. Serial Analysis of Gene Expression (SAGE) is a technology to facilitate the measurement of mRNA transcripts of normal and malignant tissues in a non-biased and highly accurate and quantitative manner. SAGE produces a comprehensive gene expression portrait witho... Current Pharmaceutical Biotechnology journals http://www.medworm.com/rss/comments.php?id=1880761 Wed, 01 Oct 2008 04:00:00 +0100 1880761 http://www.medworm.com/index.php?rid=1880760&cid=s_37014_70_f&fid=37014&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18855691%26dopt%3DAbstract Authors: Hashimoto S, Matsushima K Blood cells perform many important functions within the body, including homeostasis and host defense against various invading stimuli such as viral infection, cancer and autoimmune diseases. The subsets of leukocytes interact with each other through various surface molecules such as cytokine receptors, co-stimulation molecules and adhesion molecules. Over the last several years, accumulation of cDNA and genome databases has led to the accelerated identification of the molecules responsible for cell-cell interaction, cell activation and cell differentiation. In addition, technologies used in functional genomics, such as DNA microarray and serial analysis of gene expression (SAGE), have allowed us to analyze the expression of thousands of genes. The com... Current Pharmaceutical Biotechnology journals http://www.medworm.com/rss/comments.php?id=1880760 Wed, 01 Oct 2008 04:00:00 +0100 1880760 http://www.medworm.com/index.php?rid=1880759&cid=s_37014_70_f&fid=37014&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18855692%26dopt%3DAbstract Authors: Takamura T, Misu H, Yamashita T, Kaneko S Type 2 diabetes is a multifactorial disease that is caused by the disruption of inter-organ networks. These disruptions lead to absolute and/or relative deficiencies in the actions of insulin due to either a genetic disposition or environmental factors. Specifically, the liver plays a central role in energy homeostasis and is a major source of bioactive secretory proteins that contribute to the pathophysiology of diabetes and subsequent complications. Therefore, comprehensive gene expression analyses of critical tissues, including the liver, are important steps for understanding the molecular signature of type 2 diabetes. Serial analysis of gene expression (SAGE) techniques have made it possible to compare tag levels among independent ... Current Pharmaceutical Biotechnology journals http://www.medworm.com/rss/comments.php?id=1880759 Wed, 01 Oct 2008 04:00:00 +0100 1880759 http://www.medworm.com/index.php?rid=1880758&cid=s_37014_70_f&fid=37014&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18855693%26dopt%3DAbstract Authors: Kulshreshtha A, Zacharia AJ, Jarouliya U, Bhadauriya P, Prasad GB, Bisen PS Spirulina is a photosynthetic, filamentous, spiral-shaped and multicellular edible microbe. It is the nature's richest and most complete source of nutrition. Spirulina has a unique blend of nutrients that no single source can offer. The alga contains a wide spectrum of prophylactic and therapeutic nutrients that include B-complex vitamins, minerals, proteins, gamma-linolenic acid and the super anti-oxidants such as beta-carotene, vitamin E, trace elements and a number of unexplored bioactive compounds. Because of its apparent ability to stimulate whole human physiology, Spirulina exhibits therapeutic functions such as antioxidant, anti-bacterial, antiviral, anticancer, anti-inflammatory, anti-allergic ... Current Pharmaceutical Biotechnology journals http://www.medworm.com/rss/comments.php?id=1880758 Wed, 01 Oct 2008 04:00:00 +0100 1880758 http://www.medworm.com/index.php?rid=1880757&cid=s_37014_70_f&fid=37014&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18855694%26dopt%3DAbstract Authors: Patel RM Advances in molecular biology and biochemistry have dramatically increased our understanding of disease. The molecular mechanisms are the pathogenic basis of disease is changing modern medicine. New drugs often inhibit specific key pathways. In nuclear medicine, molecular imaging agents have been used for years, but most contrast agents for MRI or CT today are unspecific. The diagnosis is based on alterations in morphology and basic physiology, all of which are late manifestations of the original molecular changes. There are only few more specific contrast agents available. Microbubbles are the one, of size of blood cells are used as contrast agents for ultrasound imaging and are particularly valuable for targeting selected tissues and for providing useful information... Current Pharmaceutical Biotechnology journals http://www.medworm.com/rss/comments.php?id=1880757 Wed, 01 Oct 2008 04:00:00 +0100 1880757 http://www.medworm.com/index.php?rid=1880756&cid=s_37014_70_f&fid=37014&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18855695%26dopt%3DAbstract We present here a systematic study of the quenching efficiency of Förster-type energy-transfer (FRET) for multiple fluorophores immobilized on a single antibody. We simultaneously monitor the fluorescence intensity, fluorescence lifetime, and the number of available photons before photobleaching as a function of the number of identical emitters bound to a single IgG antibody. The detailed studies of FRET between individual fluorophores reveal complex through-space interactions. In general, even for two or three fluorophores immobilized on a single protein, homo-FRET interactions lead to an overall non-linear intensity increase and shortening of fluorescence lifetime. Over-labeling of protein in solution (ensemble) results in the loss of fluorescence signal due to the self-quenching of... Current Pharmaceutical Biotechnology journals http://www.medworm.com/rss/comments.php?id=1880756 Wed, 01 Oct 2008 04:00:00 +0100 1880756 http://www.medworm.com/index.php?rid=1696867&cid=s_37014_70_f&fid=37014&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18691080%26dopt%3DAbstract Authors: DeAngelis PL PMID: 18691080 [PubMed - in process] (Source: Current Pharmaceutical Biotechnology) Current Pharmaceutical Biotechnology journals http://www.medworm.com/rss/comments.php?id=1696867 Fri, 01 Aug 2008 04:00:00 +0100 1696867 http://www.medworm.com/index.php?rid=1696866&cid=s_37014_70_f&fid=37014&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18691081%26dopt%3DAbstract Authors: Balazs EA Hyaluronan solutions known as ophthalmic viscoelastic devices (OVDs) are used in surgical procedures within the eye and on the surface of the eye to prevent dryness and to facilitate wound healing. HA and a variety of derivatives facilitate procedures including vitreoretinal surgery, anterior segment surgery, glaucoma surgery, and corneal transplantation. PMID: 18691081 [PubMed - in process] (Source: Current Pharmaceutical Biotechnology) Current Pharmaceutical Biotechnology journals http://www.medworm.com/rss/comments.php?id=1696866 Fri, 01 Aug 2008 04:00:00 +0100 1696866 http://www.medworm.com/index.php?rid=1696865&cid=s_37014_70_f&fid=37014&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18691082%26dopt%3DAbstract Authors: Brown SH, Pummill PE Presently, the two main commercial sources of hyaluronic acid (HA) are rooster combs and streptococci. Harvesting from rooster combs is complex and costly. Streptococci are difficult to genetically manipulate and require complex media for growth. Both sources have potential problems with unwanted by-products, such as allergens and toxins. These problems can be solved by producing the HA with safe bacilli that are expressing a recombinant HA synthase (HAS). PMID: 18691082 [PubMed - in process] (Source: Current Pharmaceutical Biotechnology) Current Pharmaceutical Biotechnology journals http://www.medworm.com/rss/comments.php?id=1696865 Fri, 01 Aug 2008 04:00:00 +0100 1696865 http://www.medworm.com/index.php?rid=1696864&cid=s_37014_70_f&fid=37014&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18691083%26dopt%3DAbstract Authors: Prestwich GD, Kuo JW Hyaluronan (HA) is a very useful polymer, but its properties sometimes need to be altered or enhanced by chemical modification for biomedical applications. A wide variety of HA derivatives are currently used for eye surgery, joint viscoelastic supplementation, and anti-adhesion films. The future promises to deliver new classes of HA-based reagents as well as new polymers that can be used in situ with living cells or within the body. PMID: 18691083 [PubMed - in process] (Source: Current Pharmaceutical Biotechnology) Current Pharmaceutical Biotechnology journals http://www.medworm.com/rss/comments.php?id=1696864 Fri, 01 Aug 2008 04:00:00 +0100 1696864 http://www.medworm.com/index.php?rid=1696863&cid=s_37014_70_f&fid=37014&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18691084%26dopt%3DAbstract Authors: DeAngelis PL In many cases, the cellular response to hyaluronan (HA) depends on the molecular weight (MW) of the polymer chain. Most HA preparations from Nature or its derivatives possess wide size distributions called polydisperse. New chemoenzymatic synthesis technology allows the production of very narrow size distribution polymers called monodisperse. The use of stoichiometrically controlled and synchronized polymerization reactions allows an assortment of new HA reagents in the range of 10 kDa to 2,500 kDa for answering HA biology questions or potentially treating disease. PMID: 18691084 [PubMed - in process] (Source: Current Pharmaceutical Biotechnology) Current Pharmaceutical Biotechnology journals http://www.medworm.com/rss/comments.php?id=1696863 Fri, 01 Aug 2008 04:00:00 +0100 1696863 http://www.medworm.com/index.php?rid=1696862&cid=s_37014_70_f&fid=37014&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18691085%26dopt%3DAbstract Authors: Toole BP, Ghatak S, Misra S Hyaluronan (HA) polysaccharide has differential effects on cells depending on polymer size. One of the more exciting findings is that small chains or oligosaccharides of HA (6-18 sugar units), but not large polymers, will kill many types of cancer cells by triggering apoptosis while leaving normal cells unaffected. Even chemoresistant cells become drug-sensitive when co-treated with HA oligosaccharides. Overall, these observations form the basis for new anticancer therapeutics. PMID: 18691085 [PubMed - in process] (Source: Current Pharmaceutical Biotechnology) Current Pharmaceutical Biotechnology journals http://www.medworm.com/rss/comments.php?id=1696862 Fri, 01 Aug 2008 04:00:00 +0100 1696862 http://www.medworm.com/index.php?rid=1696861&cid=s_37014_70_f&fid=37014&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18691086%26dopt%3DAbstract Authors: Brown TJ Despite advances in chemotherapeutic regimens, the treatment of metastatic cancer remains a challenge. A key problem with chemotherapy drugs is nonspecific drug distribution, resulting in low tumor concentrations and systemic toxicity. The holy grail of clinical cancer research has been to establish more specific ways of directing therapeutics to tumors, whether through more targeted anti-cancer agents or via the method of delivery. Many tumor cells show up-regulated expression of receptors for the polysaccharide hyaluronan (HA), resulting in HA having a high affinity for tumors. This observation has led to the preclinical development of HA-cytotoxin bioconjugates that utilize HA as the tumor recognition moiety. The primary challenges have been organ-directed toxicity... Current Pharmaceutical Biotechnology journals http://www.medworm.com/rss/comments.php?id=1696861 Fri, 01 Aug 2008 04:00:00 +0100 1696861 http://www.medworm.com/index.php?rid=1696860&cid=s_37014_70_f&fid=37014&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18691087%26dopt%3DAbstract Authors: Azeredo J, Sutherland IW Biofilm formation occurs spontaneously on both inert and living systems and is an important bacterial survival strategy. In humans biofilms are responsible for many pathologies, most of them associated with the use of medical devices. A major problem of biofilms is their inherent tolerance to host defences and antibiotic therapies; there is therefore an urgent need to develop alternative ways to prevent and control biofilm-associated clinical infections. Several in vitro experiments have shown that phages are able to infect biofilm cells and that those phages inducing the production of depolymerases have an advantage since they can penetrate the inner layers of the biofilm by degrading components of the biofilm exopolymeric matrix. In practice clinical... Current Pharmaceutical Biotechnology journals http://www.medworm.com/rss/comments.php?id=1696860 Fri, 01 Aug 2008 04:00:00 +0100 1696860 http://www.medworm.com/index.php?rid=1696859&cid=s_37014_70_f&fid=37014&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18691088%26dopt%3DAbstract Authors: Bansal T, Garg S The concept of probiotics now has been around for more than a century, with its consumption increasing exponentially; owing to exciting scientific and clinical findings, limiting side effects of existing pharmaceutical agents and increased consumer demand for natural products. But, the evidence for their safety and efficacy has largely been anecdotal, lacking an integrated scientific basis. Clinical studies conducted with probiotics were of inadequate design and resulted in unreliable data. That is the reason why despite having innumerable potential therapeutic uses probiotics are not being universally accepted. The purpose of present article is to amalgamate various branches of research which would help in development of "better", "commercial" and "pharmaceut... Current Pharmaceutical Biotechnology journals http://www.medworm.com/rss/comments.php?id=1696859 Fri, 01 Aug 2008 04:00:00 +0100 1696859 http://www.medworm.com/index.php?rid=1696858&cid=s_37014_70_f&fid=37014&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18691089%26dopt%3DAbstract Authors: Debnath M, Bisen PS Jatropha curcas is a stress--resistant perennial plant growing on marginal soils. This plant is widespread throughout arid and semiarid tropical regions of the world and has been used as a traditional folk medicine in many countries. J.curcas is a source of several secondary metabolites of medicinal importance. The leaf, fruits, latex and bark contain glycosides, tannins, phytosterols, flavonoids and steroidal sapogenins that exhibit wide ranging medicinal properties. The plant products exhibit anti-bacterial and anti-fungal activities. The paper highlights the ability of various metabolites present in the plant to act as therapeutic agents and plant protectants. The plant is designated as an energy plant and use of J.curcas oil as biodiesel is a promising ... Current Pharmaceutical Biotechnology journals http://www.medworm.com/rss/comments.php?id=1696858 Fri, 01 Aug 2008 04:00:00 +0100 1696858 http://www.medworm.com/index.php?rid=1696857&cid=s_37014_70_f&fid=37014&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18691090%26dopt%3DAbstract Authors: Wang W, Shen S, Chen Q, Tanga B, He G, Ruan H, Das UN Silkworm pupae protein is a good source of high quality protein. The hydrolyzates of silkworm pupae protein catalyzed by neutrase, pepsin, acidic protease (Asperqiius usamii NO. 537), flavourzyme, alcalase, and trypsin with inhibitory activity on angiotensin I-converting enzyme (ACE) were identified by HPLC. The hydrolyzates catalyzed by acidic protease exerted the highest inhibitory activity on ACE. The hydrolyzing conditions were optimized by one-factor, factional factorial (FFD), and center composite (CCD) design methods, and response surface methodology (RSM). Statistical analyses showed that regression of the second-order model equation is suitable to describe ACE inhibitory bioactivity. The predicted inhibitory activi... Current Pharmaceutical Biotechnology journals http://www.medworm.com/rss/comments.php?id=1696857 Fri, 01 Aug 2008 04:00:00 +0100 1696857 http://www.medworm.com/index.php?rid=1696856&cid=s_37014_70_f&fid=37014&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18691091%26dopt%3DAbstract Authors: Thomas R, Sah NK, Sharma PB Jatropha curcas is a drought resistant, perennial plant that grows even in the marginal and poor soil. Raising Jatropha is easy. It keeps producing seeds for many years. In the recent years, Jatropha has become famous primarily for the production of biodiesel; besides this it has several medicinal applications, too. Most parts of this plant are used for the treatment of various human and veterinary ailments. The white latex serves as a disinfectant in mouth infections in children. The latex of Jatropha contains alkaloids including Jatrophine, Jatropham and curcain with anti-cancerous properties. It is also used externally against skin diseases, piles and sores among the domestic livestock. The leaves contain apigenin, vitexin and isovitexin etc. whi... Current Pharmaceutical Biotechnology journals http://www.medworm.com/rss/comments.php?id=1696856 Fri, 01 Aug 2008 04:00:00 +0100 1696856 http://www.medworm.com/index.php?rid=1696855&cid=s_37014_70_f&fid=37014&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18691092%26dopt%3DAbstract Authors: Sabisz M, Skladanowski A Caffeine and other methylxanthines produce multiple physiologic effects throughout the human body, many of these effects could potentially modulate the activity of anticancer therapy. Caffeine may directly interfere with drug transport to tumor cells by formation of mixed stacking complexes with polyaromatic drugs. If formed in cells, these complexes may also prevent of intercalating drugs from DNA binding and, in this way, lower their antitumor activity. Since many of potent carcinogens are polyaromatic compounds, formation of stacking complexes with carcinogens could be associated with anti-genotoxic activity of caffeine and its use in cancer chemoprevention. Caffeine has also been reported to inhibit ATM and ATR kinases which leads to the disruption... Current Pharmaceutical Biotechnology journals http://www.medworm.com/rss/comments.php?id=1696855 Fri, 01 Aug 2008 04:00:00 +0100 1696855 http://www.medworm.com/index.php?rid=1683947&cid=s_37014_70_f&fid=37014&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18673277%26dopt%3DAbstract Authors: Arnold U PMID: 18673277 [PubMed - in process] (Source: Current Pharmaceutical Biotechnology) Current Pharmaceutical Biotechnology journals http://www.medworm.com/rss/comments.php?id=1683947 Sun, 01 Jun 2008 04:00:00 +0100 1683947 http://www.medworm.com/index.php?rid=1680142&cid=s_37014_70_f&fid=37014&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18673277%26dopt%3DAbstract Authors: Arnold U PMID: 18673277 [PubMed - in process] (Source: Current Pharmaceutical Biotechnology) Current Pharmaceutical Biotechnology journals http://www.medworm.com/rss/comments.php?id=1680142 Sun, 01 Jun 2008 04:00:00 +0100 1680142 http://www.medworm.com/index.php?rid=1680141&cid=s_37014_70_f&fid=37014&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18673278%26dopt%3DAbstract Authors: Rosenberg HF The eosinophil-derived neurotoxin (EDN, also known as eosinophil protein-X) is best-known as one of the four major proteins found in the large specific granules of human eosinophilic leukocytes. Although it was named for its discovery and initial characterization as a neurotoxin, it is also expressed constitutively in human liver tissue and its expression can be induced in macrophages by proinflammatory stimuli. EDN and its divergent orthologs in rodents have ribonuclease activity, and are members of the extensive RNase A superfamily, although the relationship between the characterized physiologic functions and enzymatic activity remains poorly understood. Recent explorations into potential physiologic functions for EDN have provided us with some insights into its... Current Pharmaceutical Biotechnology journals http://www.medworm.com/rss/comments.php?id=1680141 Sun, 01 Jun 2008 04:00:00 +0100 1680141 http://www.medworm.com/index.php?rid=1680140&cid=s_37014_70_f&fid=37014&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18673279%26dopt%3DAbstract Authors: Boix E, Torrent M, Sánchez D, Nogués MV The eosinophil cationic protein (ECP) is a secretory ribonuclease, which is found in the eosinophilic leukocyte and involved in the innate immune system. Its cytotoxic activity is effective against a wide range of pathogens, suggesting a relatively non-specific mechanism of action. We review here the specific antipathogen activities that have been characterized for ECP. Although eosinophils and ECP are primarily associated with the host defense against nonphagocytosable pathogens, such as helminthic parasites, ECP has also an antibacterial activity, which is not shared by the other, closely-related eosinophil ribonuclease, the eosinophil derived neurotoxin (EDN). Although there is no evidence for direct involvement in vivo of e... Current Pharmaceutical Biotechnology journals http://www.medworm.com/rss/comments.php?id=1680140 Sun, 01 Jun 2008 04:00:00 +0100 1680140 http://www.medworm.com/index.php?rid=1680139&cid=s_37014_70_f&fid=37014&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18673280%26dopt%3DAbstract Authors: Carreras-Sangrà N, Alvarez-García E, Herrero-Galán E, Tomé J, Lacadena J, Alegre-Cebollada J, Oñaderra M, Gavilanes JG, Martínez-Del-Pozo A Ribotoxins constitute a family of toxic extracellular fungal RNases that exert a highly specific activity on a conserved region of the larger molecule of rRNA, known as the sarcin-ricin loop. This cleavage of a single phosphodiester bond inactivates the ribosome and leads to protein synthesis inhibition and cell death. In addition to this ribonucleolytic activity, ribotoxins can cross lipid membranes in the absence of any known protein receptor. This ability is due to their capacity to interact with acid phospholipid-containing membranes. Both activities together explain their cytotoxic character, being rather... Current Pharmaceutical Biotechnology journals http://www.medworm.com/rss/comments.php?id=1680139 Sun, 01 Jun 2008 04:00:00 +0100 1680139 http://www.medworm.com/index.php?rid=1680138&cid=s_37014_70_f&fid=37014&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18673281%26dopt%3DAbstract Authors: Arnold U By virtue of their RNA degrading catalytic activity, ribonucleases are potentially cytotoxic. For the application of these enzymes as therapeutics, however, they have to overcome several obstacles whose interplay is not yet fully understood. Ribonucleases with a basic pI are not only able to interact with the (negatively charged) cellular membrane but they are also distinctively selective for tumor cells. After the (endocytotic) uptake into the cell and release into the cytosol from the endosomes where they have to resist the attack by proteases, they face the cytosolic ribonuclease inhibitor. Only if they are able to evade the tight binding to the inhibitor (or if enough ribonuclease molecules enter the cell to neutralize the inhibitor protein) they are able to attac... Current Pharmaceutical Biotechnology journals http://www.medworm.com/rss/comments.php?id=1680138 Sun, 01 Jun 2008 04:00:00 +0100 1680138 http://www.medworm.com/index.php?rid=1680137&cid=s_37014_70_f&fid=37014&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18673282%26dopt%3DAbstract Authors: Benito A, Vilanova M, Ribó M In addition to their ribonucleolytic activity, several ribonucleases (RNases) play important roles in other specific biological activities, such as dendritic cell activation, certain pollen-induced allergies, blood vessel formation and defense against parasitic or microbial infections. Among these diverse actions, cytotoxic activity, which relies in most cases on ribonucleolytic activity, has attracted a considerable attention because of the potential for using RNases as therapeutic agents for the treatment of different malignancies. In addition to use naturally existing RNases, major efforts have been made in the development of engineered variants, which display more potent cytotoxic activity and greater selectivity for malignant cells. This ... Current Pharmaceutical Biotechnology journals http://www.medworm.com/rss/comments.php?id=1680137 Sun, 01 Jun 2008 04:00:00 +0100 1680137 http://www.medworm.com/index.php?rid=1680136&cid=s_37014_70_f&fid=37014&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18673283%26dopt%3DAbstract Authors: Futami J, Yamada H The cytotoxic properties of naturally occurring or engineered RNases correlate well with their efficiency of cellular internalization and digestion level of cellular RNA. Cationized RNases are considered to adsorb to the anionic cellular surface by Coulombic interactions, and then become efficiently internalized into cells by an endocytosis-like pathway. The design of cytotoxic RNases by chemical modification of surface carboxylic residues is one of the powerful strategies for enhancing cellular internalization and is accompanied with a decreased sensitivity for the cytoplasmic RNase inhibitor. Although chemically modified cationized RNases showed decreased ribonucleolytic activity, improved endocytosis and decreased affinity to the endogenous RNase inhibito... Current Pharmaceutical Biotechnology journals http://www.medworm.com/rss/comments.php?id=1680136 Sun, 01 Jun 2008 04:00:00 +0100 1680136 http://www.medworm.com/index.php?rid=1680135&cid=s_37014_70_f&fid=37014&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18673284%26dopt%3DAbstract Authors: Rutkoski TJ, Raines RT Onconase((R)) (ONC) is an amphibian member of the bovine pancreatic ribonuclease (RNase A) superfamily that exhibits innate antitumoral activity. ONC has been granted both orphan-drug and fast-track status by the U.S. Food and Drug Administration for the treatment of malignant mesothelioma, and is poised to become the first chemotherapeutic agent based on a ribonuclease. Investigations into the mechanism of ribonuclease-based cytotoxicity have elucidated several important determinants for cytotoxicity, including efficient deliverance of ribonucleolytic activity to the cytosol and preservation of conformation stability. Nevertheless, the most striking similarity between ONC and bovine seminal ribonuclease, another naturally cytotoxic ribonuclease, is thei... Current Pharmaceutical Biotechnology journals http://www.medworm.com/rss/comments.php?id=1680135 Sun, 01 Jun 2008 04:00:00 +0100 1680135 http://www.medworm.com/index.php?rid=1680134&cid=s_37014_70_f&fid=37014&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18673285%26dopt%3DAbstract Authors: Libonati M, Gotte G, Vottariello F After a short introduction with some examples of cytotoxic ribonucleases, the importance of natural or artificial dimerization (oligomerization) as a way for a ribonuclease to acquire novel functional properties has been pointed out. In particular, the role of the three dimensional domain swapping mechanism in bovine pancreatic ribonuclease A oligomerization, as well as its impact for the acquisition of novel biological functions (among which a remarkable antitumor action) by the enzyme protein in oligomeric form have been discussed. Finally, the structural and functional features that could explain why oligomeric ribonuclease A becomes able to display a cytotoxic activity, and the possible use and limits of the three dimensional domain-swapp... Current Pharmaceutical Biotechnology journals http://www.medworm.com/rss/comments.php?id=1680134 Sun, 01 Jun 2008 04:00:00 +0100 1680134 http://www.medworm.com/index.php?rid=1680133&cid=s_37014_70_f&fid=37014&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18673286%26dopt%3DAbstract Authors: De Lorenzo C, D'Alessio G Immunotoxins are chimeric molecules that specifically target tumor cells, as they are made up of toxins linked to an antibody directed to a specific, cell-surface tumor-associated-antigen (TAA). When the immune moiety is internalized by the tumor cell, it will carry the conjugated toxin into the cell, so that the cell will be selectively killed in a way postulated more than a hundred years ago by Paul Ehrlich, the first author to use the term magic bullet. To date, toxicity and immunogenicity have complicated the clinical use of most immunotoxins. More recently, based on the immunotoxin principle, immunoRNases have been proposed, in which the toxin moiety of immunotoxins is replaced by a non-toxic RNase. An immunoRNase (IR) is in fact an immuno-pro-to... Current Pharmaceutical Biotechnology journals http://www.medworm.com/rss/comments.php?id=1680133 Sun, 01 Jun 2008 04:00:00 +0100 1680133 http://www.medworm.com/index.php?rid=1680132&cid=s_37014_70_f&fid=37014&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18673287%26dopt%3DAbstract Authors: Ardelt W, Shogen K, Darzynkiewicz Z Rana pipiens oocytes contain two homologues of pancreatic ribonuclease A that are cytostatic and cytotoxic to human cancer cells. Extensively studied Onconase is in advanced Phase IIIb clinical trials against malignant mesothelioma, while Amphinase is a novel enzyme in pre-clinical development. Onconase is the smallest (104 amino acid residues) member of the ribonuclease A superfamily while Amphinase (114 residues) is the largest among amphibian ribonucleases. Both enzymes share the characteristic frog ribonucleases C-terminal disulfide bond but another signature of this group, the N-terminal pyroglutamate, an integral part of Onconase active site is not conserved in Amphinase. Although Onconase and Amphinase are weak catalysts their enzymat... Current Pharmaceutical Biotechnology journals http://www.medworm.com/rss/comments.php?id=1680132 Sun, 01 Jun 2008 04:00:00 +0100 1680132 http://www.medworm.com/index.php?rid=1680131&cid=s_37014_70_f&fid=37014&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18673288%26dopt%3DAbstract Authors: Rybak SM Onconase, a member of the pancreatic ribonuclease A superfamily, is currently in Phase III clinical trials for treatment of unresectable malignant mesothelioma. The anticancer effect of onconase may relate to its intracellular target, a non-coding RNA. Some non- coding RNAs are aberrantly expressed in cancer cells. This discovery is creating new interest in drugs that target RNA. Conjugating onconase to agents that recognize tumor associated molecules further increases its potency and specificity. Analysis of onconase activity when directed to two different internalizing and one non-internalizing receptor reveals that the ideal targeting agents would rapidly enter lysosomal compartments before onconase escaped to the cytosol. Antibody-onconase conjugates are effective... Current Pharmaceutical Biotechnology journals http://www.medworm.com/rss/comments.php?id=1680131 Sun, 01 Jun 2008 04:00:00 +0100 1680131 http://www.medworm.com/index.php?rid=1680130&cid=s_37014_70_f&fid=37014&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18673289%26dopt%3DAbstract Authors: Krauss J, Arndt MA, Dübel S, Rybak SM Ribonucleases (RNases) of the superfamily A exhibit potent antineoplastic activity yet do not mediate appreciable immunogenicity or non-specific toxicity in both animal models and cancer patients. Ranpirnase (Onconase((R))), the first ribonuclease being evaluated as a therapeutic in humans, has progressed to phase III clinical trials in patients with unresectable mesothelioma. Conjugation of RNases to internalizing tumor-targeting monoclonal antibodies was shown to enhance specific cell killing by several orders of magnitude both in vitro and in animal models. In this review we describe the development and current status of genetically engineered 2(nd) generation immunoRNases as promising novel anti-cancer therapeutics. PMID: 1867... Current Pharmaceutical Biotechnology journals http://www.medworm.com/rss/comments.php?id=1680130 Sun, 01 Jun 2008 04:00:00 +0100 1680130