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Selected AbstractsSurvival of human enteric viruses in the environment and foodFEMS MICROBIOLOGY REVIEWS, Issue 4 2004Artur Rze Abstract Human enteric pathogenic viruses can enter the environment through discharge of waste materials from infected persons, and be transmitted back to susceptible persons to continue the cycle of disease. Contamination of food with viruses may also promote disease outbreaks. A number of studies have investigated the survival characteristics of several enteric viruses in various environments and foodstuffs, to help explain the transmissibility of these pathogens. This review deals with published work on enteric virus survival on fomites, and in waters, soil, and foods; the results of these studies have illustrated the robust survival of viruses in these environments. Much information is lacking, however, especially for foodstuffs and soils, and no detailed information is available concerning the survival of noroviruses, the most significant foodborne type. [source] Antiadhesion molecule therapy in inflammatory bowel diseaseINFLAMMATORY BOWEL DISEASES, Issue 4 2002Dr. Gert Van Assche Abstract Adhesion molecules regulate the influx of leukocytes in normal and inflamed gut. Some of these molecules such as MadCAM-1 are specific for the gastrointestinal endothelium, but in inflammatory bowel diseases most of the adhesion factors are up-regulated. Adhesion molecules also are involved in local lymphocyte stimulation and antigen presentation within the intestinal mucosa. Recently, therapeutic compounds directed against trafficking of lymphocytes toward the gut mucosa have been designed, and are being developed as a novel class of drugs in the treatment of Crohn's disease (CD) and ulcerative colitis. This review deals with the immunological aspects of leukocyte trafficking focused on gut homing of T cells. Secondly, the changes in adhesion molecules and T-cell trafficking during intestinal inflammation are discussed. Finally, we review the clinical data that have been gathered in trials of biological therapies directed against adhesion molecules. Both antiintercellular adhesion molecule-1 (ICAM-1) and anti-,4 integrin strategies are being developed. Trials with the anti-ICAM-1 antisense oligonucleotide, ISIS-2302, in steroid-refractory CD have provided conflicting efficacy data. The anti-,4 integrin antibodies natalizumab (Antegren) and LDP-02 are in phase III and phase II trials, respectively. In the near future, these novel biological agents may prove valuable therapeutic tools in the management of refractory IBD. [source] Influences of the environment on the endocrine and paracrine fish growth hormone,insulin-like growth factor-I systemJOURNAL OF FISH BIOLOGY, Issue 6 2010M. Reinecke Insulin-like growth factor-I (IGF-I) is a key component of the complex system that regulates differentiation, development, growth and reproduction of fishes. The IGF-I gene is mainly expressed in the liver that represents the principal source of endocrine IGF-I but also in numerous other organs where the hormone most probably acts in an autocrine,paracrine manner. The primary stimulus for synthesis and release of IGF-I is growth hormone (GH) from the anterior pituitary. Thus, in analogy to mammals, it is usual to speak of a fish ,GH,IGF-I axis'. The GH,IGF-I system is affected by changes in the environment and probably represents a target of endocrine disrupting compounds (EDC) that impair many physiological processes in fishes. Thus, the review deals with the influences of changes in different environmental factors, such as food availability, temperature, photoperiod, season, salinity and EDCs, on GH gene expression in pituitary, IGF-I gene expression in liver and extrahepatic sites and the physiological effects resulting from the evoked alterations in endocrine and local IGF-I. Environmental influences certainly interact with each other but for convenience of the reader they will be dealt with in separate sections. Current trends in GH,IGF-I research are analysed and future focuses are suggested at the end of the sections. [source] Solution structure of nociceptin peptidesJOURNAL OF PEPTIDE SCIENCE, Issue 9 2002Pietro Amodeo Abstract Peptides embedded in the sequence of pre-pro-nociceptin, i.e. nociceptin, nocistatin and orphanin FQ2, have shed light on the complexity of the mechanisms involving the peptide hormones related to pain and have opened up new perspectives for the clinical treatment of pain. The design of new ligands with high selectivity and bioavailability, in particular for ORL1, is important both for the elucidation and control of the physiological role of the receptor and for their therapeutic importance. The failure to obtain agonists and antagonists when using, for nociceptin, the same substitutions that are successful for opioids, and the conformational flexibility of them all, justify systematic efforts to study the solution conformation under conditions as close as possible to their natural environment. Structural studies of linear peptides in solution are hampered by their high flexibility. A direct structural study of the complex between a peptide and its receptor would overcome this difficulty, but such a study is not easy since opioid receptors are membrane proteins. Thus, conformational studies of lead peptides in solution are still important for drug design. This review deals with conformational studies of natural pre-nociceptin peptides in several solvents that mimic in part the different environments in which the peptides exert their action. None of the structural investigations yielded a completely reliable bioactive conformation, but the global conformation of the peptides in biomimetic environments can shed light on their interaction with receptors. Copyright © 2002 European Peptide Society and John Wiley & Sons, Ltd. [source] Colloidal soft matter as drug delivery systemJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 1 2009Giulia Bonacucina Abstract Growing interest is being dedicated to soft matter because of its potential in delivering any type of drugs. Since hydrophilic, lipophilic, small and big molecules can be loaded into these colloidal systems and administered through the parenteral or nonparenteral route, soft matter systems have been used to solve many biomedical and pharmaceutical problems. In fact, they make possible to overcome difficulties in the formulation and delivery of poorly water-soluble drug molecules, settle some stability issues typical of biological drug molecules, design parenteral sustained release forms and provide functionalized soft particles that are very effective in drug targeting. This review deals with the important role that colloids play in the drug delivery and targeting, with particular attention to the more currently used systems such as microemulsions, organogels, liposomes, micelles, and dendrimers. Though significant progress has been made in drug targeting, some challenges still remain. Further efforts will be required to better understand the characteristics of targets and to discover new ones. In-depth knowledge of the physico-chemical structure and properties of the systems used for targeting is fundamental for understanding the mechanism of interaction with the biological substrate and the consequent drug release. © 2008 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 98:1,42, 2009 [source] Potential prospects of chitosan derivative trimethyl chitosan chloride (TMC) as a polymeric absorption enhancer: synthesis, characterization and applicationsJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 9 2008Jasjeet K. Sahni ABSTRACT In recent years, researchers have been working extensively on various novel properties of polymers to develop increased efficiency of drug delivery and improve bioavailability of various drug molecules, especially macromolecules. Chitosan, a naturally occurring polysaccharide, because of its protonated/polymeric nature, provides effective and safe absorption of peptide and protein drugs. Its transmucosal absorption is, however, limited to acidic media because of its strong intermolecular hydrogen bonds. A new partially quaternized chitosan derivative, N-trimethyl chitosan chloride (TMC), has been synthesized with improved solubility, safety and effectiveness as an absorption enhancer at neutral pH and in aqueous environment. It enhances the absorption, especially of peptide drugs, by reversible opening of tight junctions in between epithelial cells, thereby facilitating the paracellular diffusion of peptide drugs. This derivative thus opens new perspectives as a biomaterial for various pharmaceutical applications/drug delivery systems. This review deals with the potential use of the quaternized chitosan derivative as a permeation enhancer for the mucosal delivery of macromolecular drugs along with its other biomedical applications. [source] Emerging Role of Epigenetics in the Actions of AlcoholALCOHOLISM, Issue 9 2008Shivendra D. Shukla This review deals with the recent developments on the epigenetic effects of ethanol. A large body of data have come from studies in liver and in neuronal systems and involve post-translational modifications in histones and methylations in DNA. Ethanol causes site selective acetylation, methylation, and phosphorylation in histone. With respect to methylations the methyl group donating system involving S-adenosyl methionine appears to play a central role. There is contrasting effect of acetylation versus methylation on the same site of histone, as it relates to the transcriptional activation. Epigenetic memory also appears to correlate with liver pathology and Mallory body formation. Experimental evidence supports transcriptional regulation of genes in the CNS by DNA methylations. These studies are contributing towards a better understanding of a novel epigenetic regulation of gene expression in the context of alcohol. The critical steps and the enzymes (e.g., histone acetyltransferase, histone deacetylase, DNA methyltransferase) responsible for the epigenetic modifications are prime targets for intense investigation. The emerging data are also beginning to offer novel insight towards defining the molecular actions of ethanol and may contribute to potential therapeutic targets at the nucleosomal level. These epigenetic studies have opened up a new avenue of investigation in the alcohol field. [source] Protein sequence information by matrix-assisted laser desorption/ionization in-source decay mass spectrometryMASS SPECTROMETRY REVIEWS, Issue 5 2007Julie Hardouin Abstract Proteins from biological samples are often identified by mass spectrometry (MS) with the two following "bottom-up" approaches: peptide mass fingerprinting or peptide sequence tag. Nevertheless, these strategies are time-consuming (digestion, liquid chromatography step, desalting step), the N - (or C -) terminal information often lacks and post-translational modifications (PTMs) are hardly observed. The in-source decay (ISD) occurring in a matrix assisted laser desorption/ionization (MALDI) source appears an interesting analytical tool to obtain N -terminal sequence, to identify proteins and to characterize PTMs by a "top-down" strategy. The goal of this review deals with the usefulness of the ISD technique in MALDI source in proteomics fields. In the first part, the ISD principle is explained and in the second part, the use of ISD in proteomic studies is discussed for protein identification and sequence characterization. © 2007 Wiley Periodicals, Inc., Mass Spec Rev 26:672,682, 2007 [source] Neural control of the lower urinary tract: Peripheral and spinal mechanisms,NEUROUROLOGY AND URODYNAMICS, Issue 1 2010L. Birder Abstract This review deals with individual components regulating the neural control of the urinary bladder. This article will focus on factors and processes involved in the two modes of operation of the bladder: storage and elimination. Topics included in this review include: (1) The urothelium and its roles in sensor and transducer functions including interactions with other cell types within the bladder wall ("sensory web"), (2) The location and properties of bladder afferents including factors involved in regulating afferent sensitization, (3) The neural control of the pelvic floor muscle and pharmacology of urethral and anal sphincters (focusing on monoamine pathways), (4) Efferent pathways to the urinary bladder, and (5) Abnormalities in bladder function including mechanisms underlying comorbid disorders associated with bladder pain syndrome and incontinence. Neurourol. Urodynam. 29: 128,139, 2010. © 2009 Wiley-Liss, Inc. [source] Flavin-based Blue-light Photosensors: A Photobiophysics UpdatePHOTOCHEMISTRY & PHOTOBIOLOGY, Issue 6 2007Aba Losi This review deals with the biophysical aspects of flavin-based photosensors, comprising cryptochromes, LOV (Light, Oxygen and Voltage) and BLUF (Blue Light sensing Using FAD) proteins. Special emphasis is given to structural issues, photocycle quantum yields and energetics, mechanism of the light-triggered reactions, early stages in signal transduction and oligomeric states of the light sensing protein modules. For BLUF and LOV domains important parallels are emerging, despite their different ,/, fold arrangement, whereas there is increasing evidence for a mechanicistic and functional splitting of the cryptochrome family. [source] Targeting Allograft Injury and Inflammation in the Management of Post-Lung Transplant Bronchiolitis Obliterans SyndromeAMERICAN JOURNAL OF TRANSPLANTATION, Issue 6 2009A. G. N. Robertson Chronic allograft dysfunction, manifesting as bronchiolitis obliterans syndrome (BOS), is the major cause of morbidity and mortality in human lung transplant recipients. While alloimmunity has a definite role, there is increasing interest in overall allograft injury and subsequent inflammation and remodeling. This review deals with nonalloimmune factors that may potentiate alloimmune injury. We discuss infection and reflux/aspiration as examples of allograft injury, which may lead to chronic loss of graft function and BOS. Surgical and nonsurgical treatments aimed at preventing these insults and improving survival are considered. The need for further evidence, including randomized-controlled trials, to evaluate the role of medical and surgical therapies is emphasized by the current literature. [source] Enantioresolution of dl -penicillamineBIOMEDICAL CHROMATOGRAPHY, Issue 1 2010Ravi Bhushan Abstract Penicillamine (PenA) is a nonproteinogenic amino acid containing a thiol group. The three functional groups in penicillamine undergo characteristic chemical reactions and differ in their ability to participate in various chemical and biochemical reactions. d -penicillamine is more active pharmacologically, while the l -isomer occurs ,naturally'. This review deals with the enantioresolution of PenA both by direct and indirect methods using liquid chromatography. HPLC separation of its diastereomers prepared with different chiral derivatizing reagents (on reversed-phase columns) and separation of the derivatives prepared with achiral reagents (on chiral columns or via ligand exchange mode) has been discussed. Separation of enantiomers tagged with achiral reagent (to add a chromophore for ehanced detection) when there is no diastereomer formation has been considered separately. In addition, application of PenA and its derivatives as chiral selector for enentioresolution of certain other compounds has also been discussed. Copyright © 2009 John Wiley & Sons, Ltd. [source] O -acetylated sialic acids: Multifaceted role in childhood acute lymphoblastic leukaemiaBIOTECHNOLOGY JOURNAL, Issue 3 2009Suchandra Chowdhury Abstract Childhood acute lymphoblastic leukaemia (ALL), a malignant transformation of the lymphoblasts, is highly responsive to chemotherapy. However, due to certain inadequacy in detection of minimal residual disease (MRD), relapse is a common phenomenon. To address this question, the present review deals with the induction of an unique O -acetyl derivative of sialic acid on a few disease-associated glycoproteins and glycolipids at the onset of childhood ALL, a finding of our group in the last decade. This information has been successfully utilized for diagnosis and prognosis of the disease. Existing literature is included for comparison. Additionally, cell surface overexpression of 9- O -acetylated sialoglycoproteins and antibodies against them present in patients' sera aid the survival of the malignant lymphoblasts and suggest a multifaceted role played by these molecules. Taken together, monitoring these molecules helps not only in unravelling the biology of this paediatric malignancy but also in personalizing the treatment strategies for the betterment of the patient population. [source] Pathogenesis of osteoblastic bone metastases from prostate cancer,CANCER, Issue 6 2010Toni Ibrahim MD Abstract Prostate cancer is the second leading cause of cancer-related death in men. A typical feature of this disease is its ability to metastasize to bone. It is mainly osteosclerotic, and is caused by a relative excess of osteoblast activity, leading to an abnormal bone formation. Bone metastases are the result of a complex series of steps that are not yet fully understood and depend on dynamic crosstalk between metastatic cancer cells, cellular components of the bone marrow microenvironment, and bone matrix (osteoblasts and osteoclasts). Prostate cancer cells from primary tissue undergo an epithelial-mesenchymal transition to disseminate and acquire a bone-like phenotype to metastasize in bone tissue. This review discusses the biological processes and the molecules involved in the progression of bone metastases. Here we focus on the routes of osteoblast differentiation and activation, the crosstalk between bone cells and tumor cells, and the molecules involved in these processes that are expressed by both osteoblasts and tumor cells. Furthermore, this review deals with the recently elucidated role of osteoclasts in prostate cancer bone metastases. Certainly, to better understand the underlying mechanisms of bone metastasis and so improve targeted bone therapies, further studies are warranted to shed light on the probable role of the premetastatic niche and the involvement of cancer stem cells. Cancer 2010. © 2010 American Cancer Society. [source] Genetic and epigenetic factors involved in B-cell lymphomagenesisCANCER SCIENCE, Issue 9 2004Masao Seto Malignant lymphomas have been classified by the WHO into disease categories based not only on histological features, but also on cell surface markers, cytogenetic and clinical features. It is known that chromosome translocation plays an important role in lymphoma development, but it is not entirely clear yet why a given type of chromosome translocation is associated with a specific type of lymphoma. This review deals with molecular mechanisms of B-cell lymphoma development in association with chromosome translocations. The outcome of chromosome translo-cations can be categorized into three factors: enhancement of proliferation, inhibition of differentiation and anti-apoptotic activity. It is well known that chromosome translocation by itself cannot cause cells to become malignant because it is only one of the growth advantages leading to malignancy, while additional genetic and epigenetic alterations are required for cells to become fully malignant. Mucosa-associated lymphoid tissue (MALT) lymphomas of the stomach are unique in that a majority can be cured by Helicobacter pylori eradication, although 20 to 30% remain resistant. Others as well as we have demonstrated that the presence of the API2-MALT1 chimeric gene correlates well with resistance to H. pylori eradication treatment. These characteristics have led to the speculation that the classification of MALT lymphoma falls somewhere between tumor and inflammation. Although MALT lymphoma seems to have unique features in comparison with other types of B-cell lymphomas, it shares common molecular mechanisms with B-cell lymphoma development. [source] Preparation of enantiomerically enriched ,-aminoorganostannanes and their applications in stereoselective synthesis,CHIRALITY, Issue 10 2010Vincent Coeffard Abstract This review deals with the preparation of chiral, nonracemic ,-aminoorganostannanes and their applications in asymmetric synthesis. The pioneering works in this field date back almost 20 years ago and since then extensive research has been carried out to develop efficient and selective routes to highly enantioenriched ,-aminoorganostannanes. The facile Sn/Li transmetalation of these compounds by n -BuLi has led to various applications in stereoselective synthesis. Selected examples using chiral ,-aminoorganostannanes as starting materials will be reported. Chirality, 2010. © 2010 Wiley-Liss, Inc. [source] |