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Antiviral
Terms modified by Antiviral Selected AbstractsAntiviral and anticancer activities of 13(E)-labd-13-ene-8,,15-diol isolated from Brachyglottis monroiPHYTOTHERAPY RESEARCH, Issue 2 2010Hwa Jung Choi Abstract The antiviral activity of 13(E)-labd-13-ene-8,,15-diol (1), isolated from Brachyglottis monroi, was examined against human rhinovirus 2 (HRV2) and 3 (HRV3), and the anticancer activity on human cancer cells (A549 and Hep2). Compound (1) showed strong anti-HRV2 and HRV3 activity with a 50% inhibitory concentration (IC50) of 2.68 and 0.87,µg/mL, respectively, and a 50% cytotoxicity concentration (CC50) of 59.45,µg/mL. Ribavirin only showed anti-HRV3 activity with an IC50 of 30.48,µg/mL and a CC50 > 100,µg/mL. The addition of compound (1) to HRV-infected HeLa cells directly reduced the formation of visible cytopathic effect (CPE) and it directly interacted with HRV particles. Furthermore, A549 and Hep2 cells incubated with 32,µg/mL of compound (1) for 48,h exhibited antilung and antilaryngeal cancer activities, with a viability of less than 50%. These results suggest that compound (1) may be used as a potential antiviral and anticancer agent. Copyright © 2009 John Wiley & Sons, Ltd. [source] Synthesis, Antiviral and Cytostatic Evaluation of Unsaturated Exomethylene and Keto D -Lyxopyranonucleoside AnaloguesARCHIV DER PHARMAZIE, Issue 6 2009Niki Tzioumaki Abstract This report describes the synthesis of unsaturated exomethylene lyxopyranonucleoside analogues as potential biologically active agents. Commercially available 1,2,3,4-tetra- O -acetyl-,- D -lyxopyranose 1 was condensed with silylated thymine and uracil, respectively, deacetylated and acetalated to afford 1-(2,3- O -isopropylidene-,- D -lyxopyranosyl)thymine 4a and 1-(2,3- O -isopropylidene-,- D -lyxopyranosyl)uracil 4b. The new derivatives 1-(2,3,4-trideoxy-4-methylene-,-pent-2-enopyranosyl)thymine 8a and 1-(2,3,4-trideoxy-4-methylene-,-pent-2-enopyranosyl)uracil 8b were prepared via two different key intermediates, 7a, b and 13a, b in order to elucidate the influence of 2,,3,-unsaturation and to clarify the difference between the keto and exomethylene group on the biological activity of the target molecules. Compounds 7a, b, 8a, b, and 13a, b were evaluated for their antiviral and cytostatic activity using several virus strains and cell lines. Whereas no marked antiviral activity was noticed, 13a and 13b showed a cytostatic activity that ranged between 7 and 23 ,M for 13a and 26 and 38 ,M for 13b against murine leukemia L1210, human lymphocyte Molt4/C8 and CEM cells, and human breast carcinoma MCF7 cells. [source] Dendritic Catanionic Assemblies: In vitro Anti-HIV Activity of Phosphorus-Containing Dendrimers Bearing Gal,1cer AnaloguesCHEMBIOCHEM, Issue 12 2005Muriel Blanzat Dr. Abstract Two series of water-soluble dendritic catanionic assemblies, acting as multisite analogues of galactosylceramide (Gal,1cer), have been prepared with the goal of blocking HIV infection prior to the entry of the virus into human cells. Trifunctional and hexafunctional cinnamic acid-terminated dendrimers have been synthesized from phosphorus-containing dendrimers bearing aldehyde end groups. A classical acid,base reaction performed in water between acid-terminated dendrimers and stoichiometric amounts of N -hexadecylamino-1-deoxylactitol (3) provided the expected catanionic assemblies. Antiviral assays on these supramolecular entities confirmed the crucial roles both of multivalency effects and of lipophilicity on the biological activity of Gal,1cer analogues. Moreover, correlation between in vitro tests and molecular modeling highlights the specific influence of the assembly shape on the anti-HIV efficiency, with the tri- and hexafunctional cored dendrimers, both decorated with 12 sugar moieties, exhibiting IC50 values of 1.1 and 0.12 ,M, respectively. [source] Synthesis, Antiviral and Antitumor Activity of 2-Substituted-5-amidino-benzimidazoles.CHEMINFORM, Issue 42 2007Kristina Starcevic Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF. [source] A Synthetic Study on Antiviral and Antioxidative Chromene Derivative.CHEMINFORM, Issue 34 2006Jun Mori Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF. [source] Thiadiazolyl Quinazolones as Potential Antiviral and Antihypertensive Agents.CHEMINFORM, Issue 17 2004V. K. Pandey Abstract For Abstract see ChemInform Abstract in Full Text. [source] Infantile spasms and cytomegalovirus infection: antiviral and antiepileptic treatmentDEVELOPMENTAL MEDICINE & CHILD NEUROLOGY, Issue 9 2007Dorota Dunin-Wasowicz MD PhD From 1 January 1995 to 31 December 2004, 22 patients (13 males, nine females; age range 2-12mo) with infantile spasms and cytomegalovirus (CMV) infection were treated with intravenous ganciclovir (GCV) and antiepileptic drugs. GCV was given for 3 to 12 weeks with a 1-month interval (one, two, or three courses). Epileptic spasms occurred before (group A: eight patients), simultaneously (group B: eight patients), and after (group C: six patients) a diagnosis of human CMV (HCMV) infection and antiviral treatment. In 11 patients, DNA HCMV was found in cerebrospinal fluid by nested-polymerase chain reaction method (neuroinfection). All infants excreted CMV in urine. DNA HCMV and specific immunoglobulin M and immunoglobulin G antibodies were present in blood. Ten patients, including four with neuroinfection, have been seizure-free for at least the past 18 months. In two patients with neuroinfection, vigabatrin monotherapy was withdrawn after a 2 year 6 month seizure-free period. Eighteen patients required antiepileptic drugs polytherapy, four of whom required additional adrenocorticotropic hormone (ACTH). Six patients on polytherapy were seizure-free on follow-up, two of whom were treated with ACTH, but no patient with hypsarrhythmia who required ACTH treatment was seizure-free on follow-up. In five patients, psychomotor development was normal, 16 had tetraplegia (Gross Motor Function Classification System [GMFCS] Level V), and one had diplegia (GMFCS Level III). Early antiviral and antiepileptic therapy could result in the long-term cessation of seizures. [source] Here today , not gone tomorrow: Roles for activating receptors in sustaining NK cells during viral infectionsEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 4 2010Seung-Hwan Lee Abstract The conclusive evidence supporting a role for NK cells in defense against viruses has been obtained under conditions of NK cell deficiencies prior to infections. NK cell proliferation can be induced during infections, but the advantages of resulting expansion have been unclear because NK cell basal frequency is already high. However, NK cell decreases are also observed during certain conditions of viral infection. Given the range of potent antiviral and immunoregulatory functions of NK cells, such "disappearance" dramatically changes the resources available to the host. New studies demonstrate that proliferation dependent on activating receptors for virus-induced ligands is key for NK cell maintenance, and allows their continued availability for control of adaptive immune responses and immunopathology. This pathway for sustaining NK cells may represent a system used generally to select subsets for rescue during homeostatic purging. In the case of NK cells, though, nonselection limits continued access to the many beneficial functions of NK cells. The observations resolve the long-standing conundrum of reported NK cell increases and decreases during viral infections. Moreover, they demonstrate a previously unappreciated role for activating receptors, i.e. to keep NK cells here today and also tomorrow. [source] Molecular Interaction between a Gadolinium,Polyoxometalate and Human Serum AlbuminEUROPEAN JOURNAL OF INORGANIC CHEMISTRY, Issue 34 2009Li Zheng Abstract Polyoxometalates (POMs) show promising antibacterial, antiviral (particularly anti-HIV), antitumor, and anticancer activities, but the mechanism of these potential therapeutic effects remains to be elucidated at the molecular level. The interaction between the Gd-containing tungstosilicate [Gd(,2 -SiW11O39)2]13, and human serum albumin (HSA) was studied by several techniques. Fluorescence spectroscopy showed an energy transfer between the single tryptophan residue of HSA and the POM. Circular dichroism led to the conclusion that the POM significantly altered the secondary structure of HSA. Isothermal titration calorimetry revealed an enthalpy-driven binding reaction between HSA and the POM, resulting in the formation of a 1:1 complex.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009) [source] Synthesis and Properties of New Nucleotide Analogues Possessing Squaramide Moieties as New Phosphate Isosters,EUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 24 2005Kohji Seio Abstract New analogues of 2,-deoxynucleotides and ribonucleotides incorporating a unique squaramide structure were synthesized. Because of the strong acidity of this moiety (pKa = 2.3), these nucleotide analogues exist in a monoanionic form, which can be regarded as an electronic isoster of 5,-nucleotides under physiological conditions. The synthesis of the nucleotide analogues was achieved through the condensation of 5,- or 3,-aminonucleosides with dimethyl squarate, whilst the selective removal of the methyl group was effectively accomplished by treatment with sodium bromide. In addition, we also synthesized 3,,5,-cyclic nucleotide analogues from the 3,,5,-diazidonucleoside derivatives. NMR analysis revealed that their ribose puckering was of an N-type form, identical to that in cAMP and cGMP. Because of the unique structural, electronic, and conformational properties of squaramide-type nucleotide analogues, these analogues should be quite interesting as potential biologically active compounds such as antiviral and anticancer agents. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005) [source] Dynamic versus static models in cost-effectiveness analyses of anti-viral drug therapy to mitigate an influenza pandemicHEALTH ECONOMICS, Issue 5 2010Anna K. Lugnér Abstract Conventional (static) models used in health economics implicitly assume that the probability of disease exposure is constant over time and unaffected by interventions. For transmissible infectious diseases this is not realistic and another class of models is required, so-called dynamic models. This study aims to examine the differences between one dynamic and one static model, estimating the effects of therapeutic treatment with antiviral (AV) drugs during an influenza pandemic in the Netherlands. Specifically, we focus on the sensitivity of the cost-effectiveness ratios to model choice, to the assumed drug coverage, and to the value of several epidemiological factors. Therapeutic use of AV-drugs is cost-effective compared with non-intervention, irrespective of which model approach is chosen. The findings further show that: (1) the cost-effectiveness ratio according to the static model is insensitive to the size of a pandemic, whereas the ratio according to the dynamic model increases with the size of a pandemic; (2) according to the dynamic model, the cost per infection and the life-years gained per treatment are not constant but depend on the proportion of cases that are treated; and (3) the age-specific clinical attack rates affect the sensitivity of cost-effectiveness ratio to model choice. Copyright © 2009 John Wiley & Sons, Ltd. [source] A new strategy for studying In Vitro the drug susceptibility of clinical isolates of human hepatitis B virusHEPATOLOGY, Issue 4 2004David Durantel Resistance of hepatitis B virus (HBV) to antivirals has become a major clinical problem. Our objective was to develop a new method for the cloning of naturally occurring HBV genomes and a phenotypic assay capable of assessing HBV drug susceptibility and DNA synthesis capacity in vitro. Viral DNA was extracted from sera and was amplified by polymerase chain reaction, and amplicons were cloned into vectors that enable, after cell transfection, the initiation of the intracellular HBV replication cycle. Single or multiple clones were used to transfect Huh7 cells. The viral DNA synthesis capacity and drug susceptibility were determined by measuring the level of intracellular DNA intermediate, synthesized in absence or presence of antiviral, using Southern blot analysis. We have developed, calibrated, then used this phenotypic assay to determine the drug susceptibility of HBV quasispecies isolated throughout the course of therapy from patients selected according to their mutation profile. A multiclonal and longitudinal analysis enabled us to measure the variation of drug susceptibility of different viral quasispecies by comparison of IC50/IC90s with standards. The presence of famciclovir- or lamivudine-induced mutations in the viral population caused a change in viral DNA synthesis capacity and drug susceptibility in vitro, demonstrating the clinical relevance of the assay. In conclusion, our phenotypic assay enables the in vitro characterization of DNA synthesis capacity and drug susceptibility of HBV quasispecies isolated from patients. This assay should allow a better monitoring of patients undergoing antiviral therapy, as well as the screening of novel drugs on emerging resistant strains. (Hepatology 2004;40:855,864). [source] CD8+ T-cell interaction with HCV replicon cells: Evidence for both cytokine- and cell-mediated antiviral activityHEPATOLOGY, Issue 6 2003Chen Liu The interaction between the host immune response and infected hepatocytes plays a central role in the pathogenesis of hepatitis C virus (HCV). The lack of a suitable animal or in vitro model has hindered our understanding of the host T-cell/HCV interaction. Our aim was to develop an in vitro model to study the mechanisms of HCV-specific T-cell-mediated antiviral and cytolytic function. The HCV replicon was HLA typed and lymphocytes were obtained from an HLA class I-matched subject. CD8+ T cells were expanded with 2 HCV-specific/HLA-restricted peptides for NS3. Lymphocyte preparations were cocultured with HCV replicon (FCA1) and control (Huh7) cells labeled with 51Cr. After a 48-hour incubation, the cells were harvested for RNA extraction. Standard blocking assays were performed in the presence of anti-interferon gamma (IFN-,), anti-tumor necrosis factor , (TNF-,), and anti-FasL. Cytolytic activity was measured by 51Cr release. HCV replicon cells express homozygous HLA-A11 alleles and present HCV nonstructural proteins. HCV-specific expansion of CD8+ cells led to a 10-fold decrease in HCV replication by Northern blot analysis and 21% specific lysis of FCA1 cells (compared with 2% of control Huh7 cells). Twenty percent of this antiviral activity was independent of T-cell binding, suggesting cytokine-mediated antiviral activity. The CD8+ antiviral effect was markedly reduced by blocking either IFN-, or FasL but was unaffected by blocking TNF-,. In conclusion, HCV-specific CD8+ cells inhibit viral RNA replication by cytokine-mediated and direct cytolytic effects. This T-cell/HCV subgenomic replicon system represents a model for the investigation of CD8 cell interaction with HCV-infected hepatocytes. [source] Regulation of innate immunity against hepatitis C virus infectionHEPATOLOGY RESEARCH, Issue 2 2008Takeshi Saito Chronic hepatitis C virus (HCV) infection is a global public health problem. HCV infection is treated with type I interferon (IFN), a natural product that is produced by cells during virus infection as a result of innate immune signaling events. The secreted IFN alert the surrounding cells to turn on an "antiviral state" that resists infection. In general, the role of innate immune response is to suppress viral replication and to induce cytokines and other factors that promote adaptive immunity and the resolution of infection. The mechanisms by which the innate immune response and IFN actions limit HCV infection are not well defined, but are likely to involve the function of specific IFN-stimulated genes. HCV also copesintensively with immune responses in order to establish persistent infection. Recent studies reveal that a other viruses use similar tactics to regulate the antiviral innate immune response. In the case of HCV, innate immune signaling is strictly controlled by the viral NS3/4A protease, resulting in the disruption of IFN production. Here, we summarize the current understanding of how HCV evades the innate immune system. [source] Interferon-alpha regulates the dynamic balance between human activated regulatory and effector T cells: implications for antiviral and autoimmune responsesIMMUNOLOGY, Issue 1 2010Amit Golding Summary An adequate effector response against pathogens and its subsequent inactivation after pathogen clearance are critical for the maintenance of immune homeostasis. This process involves an initial phase of T-cell effector (Teff) activation followed by the expansion of regulatory T cells (Tregs), a unique cell population that limits Teff functions. However, significant questions remain unanswered about the mechanisms that regulate the balance between these cell populations. Using an in vitro system to mimic T-cell activation in human peripheral blood mononuclear cells (PBMC), we analysed the patterns of Treg and Teff activation, with special attention to the role of type I interferon (IFN-I). Interestingly, we found that IFN-,, either exogenously added or endogenously induced, suppressed the generation of CD4+ FoxP3HI IFN-,Neg activated Tregs (aTregs) while simultaneously promoting propagation of CD4+ FoxP3Low/Neg IFN-,Pos activated Teffs (aTeffs). We also showed that IFN-,-mediated inhibition of interleukin (IL)-2 production may play an essential role in IFN-,-induced suppression of aTregs. In order to test our findings in a disease state with chronically elevated IFN-,, we investigated systemic lupus erythematosus (SLE). Plasma from patients with SLE was found to contain IFN-I activity that suppressed aTreg generation. Furthermore, anti-CD3 activated SLE PBMCs exhibited preferential expansion of aTeffs with a very limited increase in aTreg numbers. Together, these observations support a model whereby a transient production of IFN-, (such as is seen in an early antiviral response) may promote CD4 effector functions by delaying aTreg generation, but a chronic elevation of IFN-, may tip the aTeff:aTreg balance towards aTeffs and autoimmunity. [source] Effect of rapid influenza testing on the clinical management of paediatric influenzaINFLUENZA AND OTHER RESPIRATORY VIRUSES, Issue 3 2009Lance C. Jennings Background, Rapid tests are now widely available to assist the diagnosis of influenza; implementation may optimise the use of antiviral and antibiotic agents in the clinical management of influenza. Objective, To explore the clinical management of children with influenza-like illness (ILI) when rapid influenza tests were and were not performed. Methods, Between 15 January 2007 and 30 April 2007, a standardised questionnaire was used to record the clinical features of children aged 1,12 years who presented to office-based paediatricians in Germany with febrile ILI during periods of local influenza activity. For each paediatric contact, a clinical diagnosis of either ,influenza positive', ,influenza negative' or ,suspected ILI' was made. Where performed, the outcome of a Clearview Exact Influenza A + B rapid test was recorded. Prescriptions for antiviral agents and antibiotic medications were also recorded. Results, A total of 16 907 questionnaires were evaluated. After fever (an entry criteria for all children), cough (84·6%), fatigue/decreased activity (83·0%), rhinorrhoea (73·7%) and headache (67·1%) were the most common symptoms. Influenza was clinically diagnosed in 56·8% (9596/16 907) of cases. The antiviral oseltamivir was prescribed for 24·6% (178/725) of children who were influenza positive by symptom assessment alone and 60·1% (4618/7685) of children who were influenza positive by rapid test. Antibiotics were less commonly prescribed for children who were influenza positive by rapid test [3·5% (271/7685) versus 17·2% (125/725) for symptom assessment alone]. Conclusions, In children with ILI, a positive rapid test result for influenza promotes the rational use of antiviral agents and reduces the inappropriate use of antibiotic medications. [source] Effects of interferon-,2b on keloid treatment with triamcinolone acetonide intralesional injectionINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 2 2008June Hyunkyung Lee MD Background, Triamcinolone acetonide intralesional injection (TAIL) has been used for the treatment of keloids, but only with limited success. Interferon-, (IFN-,) is the most widely used IFN, and has mainly antiviral, antiproliferative, and antitumoral functions. A few studies have evaluated the efficacy of IFN-,2b in controlled trials for the treatment of keloids. Objective, To compare the efficacy and side-effects of keloid treatment using IFN-,2b and TAIL, and TAIL only. Methods, Twenty lesions (combined TAIL + IFN-,2b group) and 20 control lesions (TAIL-only group) were studied in 19 patients (14 women and five men). The age range was 7,51 years (mean age, 24.6 years). Both groups were treated with TAIL every 2 weeks. The combined TAIL + IFN-,2b group was treated with intralesional injection of IFN-,2b, twice a week. Lesion measurements were made using thread, glue, and alginate. Results, Statistically significant decreases in depth (81.6%, P = 0.005) and volume (86.6%, P = 0.002) were observed in lesions of the combined TAIL + IFN-,2b group. In the TAIL-only group, the decreases in depth (66.0%, P = 0.281) and volume (73.4%, P = 0.245) were less statistically significant. The main side-effects were fever and flu-like symptoms, mild pain, and inflammation at the injection site. Conclusions, Intralesional IFN-,2b is an effective and safe treatment for keloids. Although the recurrence rate is as yet unknown, more than 80% improvement was noted in the majority of cases. Hence, adjuvant intralesional IFN-,2b should be considered, particularly for patients who have a history of failed corticosteroid injections. [source] RNase L: Its biological roles and regulationIUBMB LIFE, Issue 9 2006Shu-Ling Liang Abstract 2'-5'oligoadenylate-dependent ribonuclease L (RNase L) is one of the key enzymes involved in the function of interferons (IFNs), a family of cytokines participating in innate immunity against viruses and other microbial pathogens. Upon binding with its activator, 5'-phosphorylated, 2'-5' linked oligoadenylates (2-5A), RNase L degrades single-stranded viral and cellular RNAs and thus plays an important role in the antiviral and antiproliferative functions of IFNs. In recent years, evidence has revealed that RNase L displays a broad range of biological roles which are summarized in this review. iubmb Life, 58: 508-514, 2006 [source] Non-conventional signal transduction by type 1 interferons: The NF-,B pathwayJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 5 2007Ziyun Du Abstract Type I interferons (IFNs) regulate diverse cellular functions by modulating the expression of IFN-stimulated genes (ISGs) through the activation of the well established signal transduction pathway of the Janus Kinase (JAK) and signal transducers and activators of transcription (STAT) proteins. Although the JAK,STAT signal transduction pathway is critical in mediating IFN's antiviral and antiproliferative activities, other signaling pathways are activated by IFNs and regulate cellular response to IFN. The NF-,B transcription factor regulates the expression of genes involved in cell survival and immune responses. We have identified a novel IFN mediated signal pathway that leads to NF-,B activation and demonstrate that a subset of ISGs that play key roles in cellular response to IFN is regulated by NF-,B. This review focuses on the IFN-induced NF-,B activation pathway and the role of NF-,B in ISG expression, antiviral activity and apoptosis, and the therapeutic application of IFN in cancer and infectious disease. J. Cell. Biochem. 102: 1087,1094, 2007. © 2007 Wiley-Liss, Inc. [source] Enhanced type I interferon signaling and recruitment of chemokine receptor CXCR3-expressing lymphocytes into the skin following treatment with the TLR7-agonist imiquimodJOURNAL OF CUTANEOUS PATHOLOGY, Issue 4 2005Joerg Wenzel Introduction:, Imiquimod (AldaraÔ) is an immune response modifier approved for the topical treatment of external genital and perianal warts which can mediate regression of several cutaneous malignancies [basal cell carcinoma (BCC), Bowen's disease, actinic keratosis, and metastasis of malignant melanoma]. Recently, it was discovered that imiquimod acts through the toll-like receptor (TLR) 7. We hypothesize that TLR7-signaling strongly induces the production of interferon (IFN) ,, which is able to enhance Th1-mediated cellular antiviral and antitumor immunity. Patients and methods:, In the present study we analyzed the expression of MxA, a protein specifically induced by type I IFNs during topical imiquimod treatment in several patients suffering from different cutaneous malignancies (BCC, cutaneous metastasis of melanoma, and breast cancer), and characterized the inflammatory infiltrate, along with the expression of chemokine receptor CXCR3, by immunohistochemistry. Results:, Treatment with the TLR7-agonist imiquimod induced a significant lesional lymphocytic inflammation, associated with strong expression of MxA, indicating the induction of type I IFN signaling. The extent of lesional MxA staining closely correlated with the number of infiltrating T lymphocytes and the expression of the chemokine receptor CXCR3, characteristic for Th1-biased immune responses. Discussion:, Our in vivo results suggest an important role for TLR7-induced production of type I IFN, which links innate and adaptive immunity and promotes specific Th1-biased cellular immune response capable of eliminating cutaneous malignancies. MxA appears to be a valuable parameter to demonstrate IFN-type I expression in imiquimod therapy. [source] PURIFICATION AND CHARACTERIZATION OF ,-CARRAGEENASE FROM MARINE BACTERIUM MUTANT STRAIN PSEUDOALTEROMONAS SP.JOURNAL OF FOOD BIOCHEMISTRY, Issue 3 2010AJ5-13 AND ITS DEGRADED PRODUCTS ABSTRACT A ,-carrageenan-degrading bacterial strain AJ5 isolated from the intestine of Apostichopus japonicus was identified as Pseudoalteromonas sp. based on the phenotypic characters and 16S rRNA gene sequencing. The mutant Pseudoalteromonas sp. AJ5-13 with ,-carrageenase activity of 61 U/mg protein was obtained from Pseudoalteromonas sp. AJ5 using mutagenesis technique. An extracellular ,-carrageenase was purified from Pseudoalteromonas sp. AJ5-13 cultural supernatant by ammonium sulfate fractionation, gel filtration chromatography (Sephadex G-200) and cation-exchange chromatography (CM-cellulose 52). The purified enzyme yielded a single band on SDS-PAGE with the molecular mass of 35 kDa. Data of the N-terminal amino acid sequence indicated that this protein might be a novel ,-carrageenase. The pI and Km of the enzyme were 8.5 and 9.8 ± 0.2 mg/mL, respectively. The enzyme exhibited maximal activity at pH 8.0 and 55C. It hydrolyzed the ,-1, 4-glycosidic linkages of ,-carrageenan yielding ,-neocarrabiose, -tetraose, -hexaose, -octaose and -decaose sulfates as the main end-products. PRACTICAL APPLICATIONS ,-Carrageenases degrade ,-carrageenan by hydrolyzing the ,-1,4 linkages to a series of oligosaccharides. Thus, it is expected that like other ,-carrageenases, the ,-carrageenase isolated from Pseudoalteromonas sp. AJ5-13 would also be useful in seaweed biotechnology, pharmacy and immunology. ,-Carrageenases can be applied to study the composition and structure of carrageenans from different red alga, and to study the bacterial ,-carrageenan metabolism. They also provide the opportunity to investigate the structure-function relationship of the hydrolases that degrade self-associating sulfated polysaccharides. Examples of the practical applications of ,-carrageenases include their use in degrading the cell walls of seaweeds to obtain protoplasts, and in hydrolyzing ,-carrageenan to produce oligosaccharides. ,-Carrageenan-oligosaccharides have various potential biological properties, such as antiviral, antitumor, antioxidant activities, cytoprotection, immunomodulation, etc. [source] Synthesis and biological screening of some fluorinated dibenzofuran containing 3-chlorochromones and benzothiazepinesJOURNAL OF HETEROCYCLIC CHEMISTRY, Issue 4 2009Pratibha Randhavane Variously substituted chalcones were synthesized from 4-difluoromethoxy-dibenzofuran-1-carboxaldehyde. These chalcones were converted into corresponding 3-chlorochromones and dihydro-benzothiazepines. Synthesized compounds were tested for their antifungal, antibacterial, antiviral and antioxidant activities. J. Heterocyclic Chem., (2009). [source] Synthesis of oxazolo[3,2- b]hetero[1,2,4]thiadiazine S,S-dioxides ,JOURNAL OF HETEROCYCLIC CHEMISTRY, Issue 5 2005Salvador Vega Six bromomethyl derivatives of the new 2,3-dihydrooxazolo[3,2- b]thieno[3,4- e][1,2,4]thiadiazine 5,5-dioxides, 2,3-dihydrooxazolo[3,2- b]thieno[2,3- e][1,2,4]thiadiazine 5,5-dioxides and 6,7-dihydrooxazolo-[3,2- b]pyrazolo[4,3- e][1,2,4]thiadiazine 9,9-dioxides heterocyclic ring systems were synthesized. These compounds are good intermediates for the preparation and development of promising antiviral and psy-chotropic drugs. The structures of the products are supported by different nmr spectroscopic methods and mass spectrometry. [source] Cytokine responses in a severe case of glandular fever treated successfully with foscarnet combined with prednisolone and intravenous immunoglobulinJOURNAL OF MEDICAL VIROLOGY, Issue 1 2009Christine Ma Abstract Viral loads and cytokine responses Epstein,Barr virus (EBV) were measured in an 18-year-old boy with severe glandular fever complicated by a mild anaemia, severe thrombocytopaenia and neutropaenia. Hepatosplenomegaly was detected by abdominal ultrasound in the presence of significant hepatitis. Cytokine testing demonstrated elevated cell-mediated Th1 (IFN-,, IL-12, sTNFR1, CXCL10, CXCL9 and CCL3) and humoral Th2 (IL-4) immune responses. Serum antibodies to EBV virus capsid antigen (VCA) IgM and IgG antibodies were detected, together with a raised EBV DNA level (up to about 70,000 DNA copies/mL) in the acute phase of the illness. This EBV DNA load decreased rapidly in response to treatment with a combination of foscarnet, intravenous immunoglobulin and prednisolone, and the boy's symptoms settled eventually after approximately 50 days of illness, following this combined antiviral and immune-modulating therapy. Detailed immunological, virological, haematological and biochemical laboratory parameters are presented to document this patient's severe EBV disease and eventual recovery. J. Med. Virol. 81:99,105, 2009. © 2008 Wiley-Liss, Inc. [source] Antibacterial, antiviral, antiproliferative and apoptosis-inducing properties of Brackenridgea zanguebarica (Ochnaceae)JOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 8 2006Maren Möller Brackenridgea zanguebarica is a small tree that is used in traditional African medicine as a type of cure-all for many diseases, including the treatment of wounds. The yellow bark of B. zanguebarica was used for the preparation of an ethanolic extract, which was tested in various concentrations against eleven bacteria, Herpes simplex virus type 1 (HSV-1) and different human tumour cell lines. The extract that contains different polyphenolic substances like calodenin B. Cell growth inhibition, assessed via MTT-assay, was found in all tested human cell lines with IC50 values (concentration of extract that reduced cell viability by 50%) between 33 ,g dry extract/mL for HL-60 human myeloid leukaemia cells and 93 ,g dry extract/mL for HaCaT human keratinocytes. Staining with Annexin-V-FLUOS and JC-1 followed by subsequent analysis via flow cytometry revealed significant apoptosis-inducing properties. Analysis of caspase activity using a fluorogenic caspase-3 substrate showed a significant caspase activity in Jurkat T-cells after incubation with the extract. The bark extract had a pronounced activity against free HSV-1 and a strong antibacterial activity against Gram-positive strains (MICs: 6,24 ,g dry extract/mL), which are often involved in skin infections. Additionally, no irritating properties of the extract could be observed in hen-egg test chorioallantoic membrane (HET-CAM) assay. These findings give a rationale for the traditional use of B. zanguebarica and are a basis for further analysis of the plant's components, their biological activity, and its use in modern phytotherapy. [source] MICROALGAE AND CYANOBACTERIA: FOOD FOR THOUGHT,JOURNAL OF PHYCOLOGY, Issue 2 2008Miroslav Gantar In non-Western civilizations, cyanobacteria have been part of the human diet for centuries. Today, microalgae and cyanobacteria are either produced in controlled cultivation processes or harvested from the natural habitats and marketed as food supplements around the world. Cyanobacteria produce a vast array of different biologically active compounds, some of which are expected to be used in drug development. The fact that some of the active components from cyanobacteria potentially have anticancer, antimicrobial, antiviral, anti-inflammatory, and other effects is being used for marketing purposes. However, introduction of these products in the form of whole biomass for alimentary purposes raises concerns regarding the potential toxicity and long-term effects on human health. Here, we review data on the use of cyanobacteria and microalgae in human nutrition and searched for available information on legislature that regulates the use of these products. We have found that, although the quality control of these products is most often self-regulated by the manufacturers, different governmental agencies are introducing strict regulations for placing novel products, such as algae and cyanobacteria, on the market. The existing regulations require these products to be tested for the presence of toxins, such as microcystin; however, other, sometimes novel, toxins remain undetected, and their long-term effects on human health remain unknown. [source] Review article: influenza A (H1N1) virus in patients with inflammatory bowel diseaseALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 1 2010J.-F. RAHIER Summary Background, Infection with influenza A (H1N1)v (swine flu) has caused widespread anxiety, among patients who are potentially immunocompromised, such as those being treated for inflammatory bowel disease. Aim, To provide guidance for physicians and their patients on the risk, prevention and management of influenza A (H1N1)v infection. Methods, Medline was searched using the following key words: ,swine flu', ,immunosuppression', inflammatory bowel disease', ,recommendations', ,immunization', ,vaccination'. Organizations such as European Centre for Disease Prevention and Control, the Centers for Disease Control and Prevention and the World Health Organization were consulted for recent papers and recommendations regarding immunocompromised patients and influenza A (H1N1)v infection. Results, Pandemic influenza A (H1N1) virus predominantly affects young patients. Those who are immunocompromised because of underlying disease or treatment are considered at higher risk of complications from influenza A (H1N1). They should be offered prevention (vaccination, postexposure prophylaxis) or treatment with antiviral drugs, if affected. Pneumococcal infection is a complication of influenza infection; therefore, pneumococcal vaccination appears advisable. Seasonal influenza vaccination is also recommended. Withdrawal of immunosuppressive treatment appears advisable during severe active infection if possible. Conclusions, Pragmatic advice is the best that can be offered in the current circumstances because of paucity of evidence. Investigation into the impact of influenza A (H1N1)v infection in young people with chronic conditions is needed. [source] Review article: current antiviral therapy of chronic hepatitis BALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 2 2008W. S. AYOUB Summary Background, The long-term goals of therapy for chronic hepatitis B are to reduce serum HBV DNA to low or undetectable levels and ultimately reduce or prevent the development of cirrhosis and hepatocellular carcinoma. Aim, To review the current treatment of chronic hepatitis B, with a focus on diagnosis and management of resistance and active management of suboptimal responses. Methods, A systematic review of the literature, with a focus on recent guidelines, was undertaken. Results, Among the six drugs licensed for the treatment of chronic hepatitis B in the US, the preferred agents in 2008 will include entecavir, peginterferon alfa-2a, possibly telbivudine, and tenofovir following licensure. When using an oral agent, a major focus of management is on the selection of a drug with high potency and low rate of resistance, and active on-treatment management to optimize therapy. Preventing the sequelae of antiviral drug resistance and appropriate management when resistance is initially detected are also the major focus of current management. The addition of an antiviral agent that is not cross-resistant is critical to restore suppression of viral replication. Conclusions, Newer agents and modified treatment strategies, especially using combination therapy, hold promise to optimize the management of patients with chronic hepatitis B by achieving the high potency and the lowest rate of resistance. [source] Inosine monophosphate dehydrogenase (IMPDH) as a target in drug discoveryMEDICINAL RESEARCH REVIEWS, Issue 2 2008Qingning Shu Abstract Inosine monophosphate dehydrogenase (IMPDH) is a key enzyme of de novo purine nucleotide biosynthesis and is viewed as an important target in the quest for discovery of drugs in the antiviral, antibacterial and anticancer therapeutic areas. This review focuses on the medicinal chemistry, drug discovery and chemical biology of IMPDH. Examples of IMP and cofactor site-directed inhibitors, allosteric inhibitors and isoform-selective inhibitors are presented. Comparison of IMPDHs from different organisms is also made to facilitate the design of species-selective IMPDH inhibitors for drug discovery. Special emphasis in the review is placed on IMPDH from Mycobacterium tuberculosis. © 2007 Wiley Periodicals, Inc. Med Res Rev, 28, No. 2, 219,232, 2008 [source] Design of translactam HCMV protease inhibitors as potent antiviralsMEDICINAL RESEARCH REVIEWS, Issue 4 2005Alan D. Borthwick Abstract Human cytomegalovirus (HCMV) is an important pathogen for which there is a significant unmet medical need. New HCMV antivirals, active against novel molecular targets, are undoubtedly needed as the currently available drugs ganciclovir, cidofovir, and foscarnet, which are all viral DNA inhibitors, suffer from limited effectiveness, mainly due to the development of drug resistance, poor bioavailability, and toxicity. One of the newer molecular targets that has been exploited in the search for better drug candidates is HCMV protease. Our ,Ala HCMV protease (wild type variant with the internal cleavage site deleted) was cloned and expressed in E. coli. This viral enzyme was used to develop HCMV protease assays to evaluate potential inhibitors. The chirally pure (SRS)-,-methyl pyrrolidine-5,5- trans -lactam template was synthesized, which together with the natural substrate requirements of HCMV protease and detailed SAR, was used to design potent and selective mechanism based inhibitors of HCMV protease. The mechanism of action of these inhibitors of HCMV protease was investigated by ESI/MS, and the X-ray crystal structure of the HCMV protease was used to refine our selective viral enzyme inhibitors to obtain plasma stable antivirals. A novel ELISA antiviral assay was developed which, together with a cytotoxicity assay, enabled us to discover anti-HCMV drug candidates equivalent in potency to ganciclovir that had good pharmacokinetics in the dog and good brain and ocular penetration in the guinea pig. © 2005 Wiley Periodicals, Inc. Med Res Rev. [source] | ||||||||||||||||||||||||||||||||||||||||