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Sample records for antiviral treatment initiation

  1. Determinants of Antiviral Treatment Initiation in a Hepatitis C-infected Population Benefiting from Universal Health Care Coverage

    Directory of Open Access Journals (Sweden)

    Romain Moirand

    2007-01-01

    Full Text Available BACKGROUND AND AIMS: In view of increasing therapeutic efficacy, the delivery of hepatitis C virus (HCV antiviral treatment is expected to increase. Yet practical experience reveals a low rate of treatment, particularly among intravenous drug users. The aim of the present study was to examine the prevalence of HCV treatment and identify factors associated with HCV treatment in a population of patients evaluated in an academic hepatology outpatient clinic between 2001 and 2002.

  2. Bell's Palsy: Treatment with Steroids and Antiviral Drugs

    Science.gov (United States)

    ... PATIENTS and their FAMILIES BELL’S PALSY: TREATMENT WITH STEROIDS AND ANTIVIRAL DRUGS This information sheet is provided to help you understand the role of steroids and antiviral drugs for treating Bell’s palsy. Neurologists ...

  3. Antiviral Treatment among Pregnant Women with Chronic Hepatitis B

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    Lin Fan

    2014-01-01

    Full Text Available Objective. To describe the antiviral treatment patterns for chronic hepatitis B (CHB among pregnant and nonpregnant women. Methods. Using 2011 MarketScan claims, we calculated the rates of antiviral treatment among women (aged 10–50 years with CHB. We described the pattern of antiviral treatment during pregnancy and ≥1 month after delivery. Results. We identified 6274 women with CHB during 2011. Among these, 64 of 507 (12.6% pregnant women and 1151 of 5767 (20.0% nonpregnant women received antiviral treatment (P < 0.01. Pregnant women were most commonly prescribed tenofovir (73.4% and lamivudine (21.9%; nonpregnant women were most commonly prescribed tenofovir (50.2% and entecavir (41.3% (P < 0.01. Among 48 treated pregnant women with an identifiable delivery date, 16 (33.3% were prescribed an antiviral before pregnancy and continued treatment for at least one month after delivery; 14 (29.2% started treatment during the third trimester and continued at least one month after delivery. Conclusion. Among this insured population, pregnant women with CHB received an antiviral significantly less often than nonpregnant women. The most common antiviral prescribed for pregnant women was tenofovir. These data provide a baseline for assessing changes in treatment patterns with anticipated increased use of antivirals to prevent breakthrough perinatal hepatitis B virus infection.

  4. Antiviral Treatment among Pregnant Women with Chronic Hepatitis B

    Science.gov (United States)

    Fan, Lin; Owusu-Edusei, Kwame; Schillie, Sarah F.; Murphy, Trudy V.

    2014-01-01

    Objective. To describe the antiviral treatment patterns for chronic hepatitis B (CHB) among pregnant and nonpregnant women. Methods. Using 2011 MarketScan claims, we calculated the rates of antiviral treatment among women (aged 10–50 years) with CHB. We described the pattern of antiviral treatment during pregnancy and ≥1 month after delivery. Results. We identified 6274 women with CHB during 2011. Among these, 64 of 507 (12.6%) pregnant women and 1151 of 5767 (20.0%) nonpregnant women received antiviral treatment (P < 0.01). Pregnant women were most commonly prescribed tenofovir (73.4%) and lamivudine (21.9%); nonpregnant women were most commonly prescribed tenofovir (50.2%) and entecavir (41.3%) (P < 0.01). Among 48 treated pregnant women with an identifiable delivery date, 16 (33.3%) were prescribed an antiviral before pregnancy and continued treatment for at least one month after delivery; 14 (29.2%) started treatment during the third trimester and continued at least one month after delivery. Conclusion. Among this insured population, pregnant women with CHB received an antiviral significantly less often than nonpregnant women. The most common antiviral prescribed for pregnant women was tenofovir. These data provide a baseline for assessing changes in treatment patterns with anticipated increased use of antivirals to prevent breakthrough perinatal hepatitis B virus infection. PMID:25548510

  5. Antiviral Treatment among Pregnant Women with Chronic Hepatitis B

    OpenAIRE

    Lin Fan; Kwame Owusu-Edusei; Schillie, Sarah F.; Murphy, Trudy V.

    2014-01-01

    Objective. To describe the antiviral treatment patterns for chronic hepatitis B (CHB) among pregnant and nonpregnant women. Methods. Using 2011 MarketScan claims, we calculated the rates of antiviral treatment among women (aged 10–50 years) with CHB. We described the pattern of antiviral treatment during pregnancy and ≥1 month after delivery. Results. We identified 6274 women with CHB during 2011. Among these, 64 of 507 (12.6%) pregnant women and 1151 of 5767 (20.0%) nonpregnant women receiv...

  6. Antiviral treatment for Bell's palsy (idiopathic facial paralysis

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    Ildiko Gagyor

    Full Text Available ABSTRACTBACKGROUND: Corticosteroids are widely used in the treatment of idiopathic facial paralysis (Bell's palsy, but the effectiveness of additional treatment with an antiviral agent is uncertain. Significant morbidity can be associated with severe cases of Bell's palsy.OBJECTIVES: To assess the effects of antiviral treatments alone or in combination with any other therapy for Bell's palsy.METHODS:Search methods:On 7 October 2014 we searched the Cochrane Neuromuscular Disease Group Specialized Register, CENTRAL, MEDLINE, EMBASE, LILACS, DARE, NHS EED, and HTA. We also reviewed the bibliographies of the identified trials and contacted trial authors and known experts in the field and relevant drug companies to identify additional published or unpublished data. We searched clinical trials registries for ongoing studies.Selection criteria:We considered randomised controlled trials or quasi-randomised controlled trials of antivirals with and without corticosteroids versus control therapies for the treatment of Bell's palsy.We excluded trials that had a high risk of bias in several domains.Data collection and analysis:Pairs of authors independently assessed trials for relevance, eligibility, and risk of bias, using standard Cochrane procedures.MAIN RESULTS: Eleven trials, including 2883 participants, met the inclusion criteria and are included in the final analysis. We added four studies to the previous review for this update. Some of the trials were small, and a number were at high or unclear risk of bias. Other trials did not meet current best standards in allocation concealment and blinding. Incomplete recovery:We found no significant benefit from adding antivirals to corticosteroids in comparison with corticosteroids alone for people with Bell's palsy (risk ratio (RR 0.69, 95% confidence interval (CI 0.47 to 1.02, n = 1715. For people with severe Bell's palsy (House Brackmann scores of 5 and 6 or the equivalent in other scales, we found a

  7. Prophylactic Antiviral Treatment in Recurrent Herpes Zoster: A Case Report

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    Hatice Gamze Bayram

    2011-06-01

    Full Text Available Herpes zoster (HZ occurs in older ages with activation of varicella-zoster virus (VZV which persists in a dormant phase within the dorsal root ganglia. The incidence of HZ in immunosuppressed patients is 20-100 times higher and the clinical progress is more severe than in immunocompetent individuals. A 48-year-old man who had been diagnosed with acute myelocytic leukemia type M3 and had been treated with immunosuppressive agents was admitted to our clinic. The patient was clinically diagnosed as having HZ. He was treated with acyclovir 800 mg five times daily for 7 days. In the consecutive three months, he attended our clinic again with similar complaints. The left cervical (C5, C6 dermatomes were involved at the fourth attack of HZ. Multinucleated giant cells were determined on the Tzanck smear. VZV DNA was detected by polymerase chain reaction (PCR. Treatment with valacyclovir 1 g three times daily for 14 days was prescribed and then, prophylactic treatment with valacyclovir 500 mg two times a day was administered. Although immunosuppressive treatment was continued, no new attacks of herpes zoster occurred. We think that prophylactic antiviral therapy should be initiated in immunosuppressive individuals who have recurrent herpes zoster attacks.

  8. Antiviral treatment for chronic hepatitis C in patients with human immunodeficiency virus

    DEFF Research Database (Denmark)

    Iorio, Alfonso; Marchesini, Emanuela; Awad, Tahany;

    2010-01-01

    Antiviral treatment for chronic hepatitis C may be less effective if patients are co-infected with human immunodeficiency virus (HIV).......Antiviral treatment for chronic hepatitis C may be less effective if patients are co-infected with human immunodeficiency virus (HIV)....

  9. Causes of treatment failure for hepatitis C in the era of direct-acting antiviral therapy.

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    Cabezas, Joaquín; Llerena, Susana; Puente, Ángela; Fábrega, Emilio; Crespo, Javier

    2016-07-01

    Hepatitis C therapy in the era of the newer direct-acting antiviral agents has radically changed our treatment schemes by achieving very high rates of sustained virological response. However, treatment with direct antiviral agents fails in a subgroup of patients. This group of so-called difficult-to-treat individuals is the subject of this paper, which reviews the causes of virological failure, their clinical implications, and some final recommendations.

  10. Depletion of elongation initiation factor 4E binding proteins by CRISPR/Cas9 enhances the antiviral response in porcine cells.

    Science.gov (United States)

    Ramírez-Carvajal, Lisbeth; Singh, Neetu; de los Santos, Teresa; Rodríguez, Luis L; Long, Charles R

    2016-01-01

    Type I interferons (IFNs) are key mediators of the innate antiviral response in mammalian cells. Elongation initiation factor 4E binding proteins (4E-BPs) are translational controllers of interferon regulatory factor 7 (IRF-7), the "master regulator" of IFN transcription. Previous studies have suggested that mouse cells depleted of 4E-BPs are more sensitive to IFNβ treatment and had lower viral loads as compared to wild type (WT) cells. However, such approach has not been tested as an antiviral strategy in livestock species. In this study, we tested the antiviral activity of porcine cells depleted of 4E-BP1 by a Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/CRISPR-associated protein-9 nuclease (Cas9) genome engineering system. We found that 4E-BP1 knockout (KO) porcine cells had increased expression of IFNα and β, IFN stimulated genes, and significant reduction in vesicular stomatitis virus titer as compare to WT cells. No phenotypical changes associated with CRISPR/Cas9 manipulation were observed in 4E-BP1 KO cells. This work highlights the use of the CRISPR/Cas9 system to enhance the antiviral response in porcine cells.

  11. Antiviral treatment of a boy with EBV-associated hydroa vacciniforme

    DEFF Research Database (Denmark)

    Mose, Anja Pahlow; Fisker, Niels; Clemmensen, Ole;

    2014-01-01

    Hydroa vacciniforme is one of the rarest forms of photosensitivity disorders of the skin. Effective treatment options are scarce and mainly constitute of strict sun protection. Lately, hydroa vacciniforme has been associated with Epstein-Barr virus infection. We present a patient with hydroa...... vacciniforme and concomitant previous/chronic Epstein-Barr virus infection. In this case, antiviral treatment was successful....

  12. Antiviral treatment in patients with cytomegalovirus positive ulcerative colitis

    Institute of Scientific and Technical Information of China (English)

    Kadir; Ozturk

    2014-01-01

    Cytomegalovirus(CMV) is a common virus in patients with ulcerative colitis receiving immunosuppressive drugs. Many studies suggested that CMV infection is an exacerbating factor in patients with ulcerative colitis. The role of CMV in exacerbations of ulcerative colitis has been discussed. One of studies starting this discussion is an article entitled "CMV positive ulcerative colitis: A single center experience and literature review" by Kopylov et al. However, we think that there are some points that should be emphasized about the study. Especially, the small number of patients in the study has led to meaningless results. Large controlled prospective trials are needed to clarify the benefit of antiviral therapy for active ulcerative colitis patients.

  13. Chronic Hepatitis C and Antiviral Treatment Regimens: Where Can Psychology Contribute?

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    Evon, Donna M.; Golin, Carol E.; Fried, Michael W.; Keefe, Francis J.

    2013-01-01

    Objective: Our goal was to evaluate the existing literature on psychological, social, and behavioral aspects of chronic hepatitis C viral (HCV) infection and antiviral treatment; provide the state of the behavioral science in areas that presently hinder HCV-related health outcomes; and make recommendations for areas in which clinical psychology…

  14. Viral Response to Specifically Targeted Antiviral Therapy for Hepatitis C and the Implications for Treatment Success

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    Curtis L Cooper

    2010-01-01

    Full Text Available Currently, hepatitis C virus (HCV antiviral therapy is characterized by long duration, a multitude of side effects, difficult administration and suboptimal success; clearly, alternatives are needed. Collectively, specifically targeted antiviral therapy for HCV (STAT-C molecules achieve rapid viral suppression and very high rapid virological response rates, and improve sustained virological response rates. The attrition rate of agents within this class has been high due to various toxicities. Regardless, several STAT-C molecules are poised to become the standard of care for HCV treatment in the foreseeable future. Optimism must be tempered with concerns related to the rapid development of drug resistance with resulting HCV rebound. Strategies including induction dosing with interferon and ribavirin, use of combination high-potency STAT-C molecules and an intensive emphasis on adherence to HCV antiviral therapy will be critical to the success of this promising advance in HCV therapy.

  15. Optimal Control of Hepatitis C Antiviral Treatment Programme Delivery for Prevention amongst a Population of Injecting Drug Users

    OpenAIRE

    Martin, Natasha K.; Pitcher, Ashley B.; Vickerman, Peter; Vassall, Anna; Hickman, Matthew

    2011-01-01

    In most developed countries, HCV is primarily transmitted by injecting drug users (IDUs). HCV antiviral treatment is effective, and deemed cost-effective for those with no re-infection risk. However, few active IDUs are currently treated. Previous modelling studies have shown antiviral treatment for active IDUs could reduce HCV prevalence, and there is emerging interest in developing targeted IDU treatment programmes. However, the optimal timing and scale-up of treatment is unknown, given the...

  16. Optimal Control of Hepatitis C Antiviral Treatment Programme Delivery for Prevention amongst a Population of Injecting Drug Users

    OpenAIRE

    Martin, NK; Pitcher, AB; Vickerman, P.; Vassall, A; Hickman, M

    2011-01-01

    : In most developed countries, HCV is primarily transmitted by injecting drug users (IDUs). HCV antiviral treatment is effective, and deemed cost-effective for those with no re-infection risk. However, few active IDUs are currently treated. Previous modelling studies have shown antiviral treatment for active IDUs could reduce HCV prevalence, and there is emerging interest in developing targeted IDU treatment programmes. However, the optimal timing and scale-up of treatment is unknown, given t...

  17. Antiviral treatment for chronic hepatitis B in renaltransplant patients

    Institute of Scientific and Technical Information of China (English)

    Ezequiel Ridruejo

    2015-01-01

    Chronic hepatitis B infection is frequent in renaltransplant patients. It negatively impacts long termoutcomes reducing graft and patient survival. Currentguidelines clearly define who needs treatment, whento start, what is the first line therapy, how to monitortreatment response, when to stop, and how patientsmust be controlled for its safety. There is some datashowing a favorable safety and efficacy profile ofnucleos(t)ide analogue (NUC) treatment in the renaltransplant setting. Entecavir, a drug without majorsigns of nephrotoxicity, appears to be the first optionfor NUC na?ve patients and tenofovir remains thepreferred choice for patients with previous resistanceto lamivudine or any other NUC. Renal transplantrecipients under antiHBV therapy should be monitoredfor its efficacy against HBV but also for its safety witha close renal monitoring. Studies including a largenumber of patients with long term treatment and followup are still needed to better demonstrate the safetyand efficacy of newer NUCs in this population.

  18. To test or to treat? An analysis of influenza testing and antiviral treatment strategies using economic computer modeling.

    Directory of Open Access Journals (Sweden)

    Bruce Y Lee

    Full Text Available BACKGROUND: Due to the unpredictable burden of pandemic influenza, the best strategy to manage testing, such as rapid or polymerase chain reaction (PCR, and antiviral medications for patients who present with influenza-like illness (ILI is unknown. METHODOLOGY/PRINCIPAL FINDINGS: We developed a set of computer simulation models to evaluate the potential economic value of seven strategies under seasonal and pandemic influenza conditions: (1 using clinical judgment alone to guide antiviral use, (2 using PCR to determine whether to initiate antivirals, (3 using a rapid (point-of-care test to determine antiviral use, (4 using a combination of a point-of-care test and clinical judgment, (5 using clinical judgment and confirming the diagnosis with PCR testing, (6 treating all with antivirals, and (7 not treating anyone with antivirals. For healthy younger adults ( or = 65 years old, in both seasonal and pandemic influenza scenarios, employing PCR was the most cost-effective option, with the closest competitor being clinical judgment (when judgment accuracy > or = 50%. Point-of-care testing plus clinical judgment was cost-effective with higher probabilities of influenza. Treating all symptomatic ILI patients with antivirals was cost-effective only in older adults. CONCLUSIONS/SIGNIFICANCE: Our study delineated the conditions under which different testing and antiviral strategies may be cost-effective, showing the importance of accuracy, as seen with PCR or highly sensitive clinical judgment.

  19. Antiviral Medications for Treatment of 2009 H1N1 Influenza and Pregnancy

    Centers for Disease Control (CDC) Podcasts

    2009-11-09

    This podcast features CDC's Dr. Sonja Rasmussen discussing the latest guidelines related to antiviral medications for treatment of 2009 H1N1 Influenza. Excerpt from a CDC-Medscape video series for physicians, nurses, pharmacists, and other healthcare professionals.  Created: 11/9/2009 by National Center for Health Marketing (NCHM); National Center on Birth Defects and Developmental Disabilities (NCBDDD).   Date Released: 1/21/2010.

  20. Prevention and Treatment of KSHV-associated Diseases with Antiviral Drugs

    Institute of Scientific and Technical Information of China (English)

    Ren-rong TIAN; Qing-jiao LIAO; Xulin CHEN

    2008-01-01

    s Kaposi's sarcoma-associated herpesvirus (KSHV) was first identified as the etiologic agent of Kaposi's sarcoma (KS) in 1994.KSHV infection is necessary,but not sufficient for the development of Kaposi sarcoma (KS),primary effusion lymphoma (PEL),and multicentric Castleman disease (MCD).Advances in the prevention and treatment of KSHV-associated Diseases have been achieved,even though current treatment options are ineffective,or toxic to many affected persons.The identification of new targets for potential future therapies and the randomized trial to evaluate the efficacy of new antivirals are required.

  1. Early gene activation initiates neuroinflammation prior to VSV neuroinvasion: Impact on antiviral responses and sleep.

    Science.gov (United States)

    Ciavarra, Richard P; Lundberg, Patric; Machida, Mayumi; Ambrozewicz, Marta A; Wellman, Laurie L; Breving, Kimberly; Steel, Christina; Sanford, Larry D

    2017-02-15

    Rapid eye movement (REM) sleep is rapidly and persistently suppressed during vesicular stomatitis virus (VSV) encephalitis in C57Bl/6J (B6) mice. REM sleep suppression was associated with a complex global brain chemokine/cytokine response with bimodal kinetics although regionally distinct cytokine profiles were readily identified. Cytokine mRNA was translated either immediately or suppressed until the pathogen was cleared from the CNS. Innate signaling pathway (TLRs, RIG-I) activation occurred rapidly and sequentially prior to VSV neuroinvasion suggesting that antiviral states are quickly established in the CNS in advance of viral pathogen penetration. Il1β suppressed REM sleep mimicking aspects of VSV-induced sleep alterations whereas some robustly induced chemokines may be protective of REM. Thus, multiple brain chemokines may mediate sleep across VSV encephalitis via differential somnogenic effects.

  2. New antiviral targets for innovative treatment concepts for hepatitis B virus and hepatitis delta virus.

    Science.gov (United States)

    Durantel, David; Zoulim, Fabien

    2016-04-01

    Current therapies of chronic hepatitis B (CHB) remain limited to pegylated-interferon-alpha (PegIFN-α) or any of the five approved nucleos(t)ide analogues (NUC) treatments. While viral suppression can be achieved in the majority of patients with the high-barrier-to-resistance new-generation of NUC, i.e. entecavir and tenofovir, HBsAg loss is achieved by PegIFN-α and/or NUC in only 10% of patients, after a 5-year follow-up. Attempts to improve the response by administering two different NUC or a combination of NUC and PegIFN-α have not provided a dramatic increase in the rate of functional cure. Because of this and the need of long-term NUC administration, there is a renewed interest regarding the understanding of various steps of the HBV replication cycle, as well as specific virus-host cell interactions, in order to define new targets and develop new antiviral drugs. This includes a direct inhibition of viral replication with entry inhibitors, drugs targeting cccDNA, siRNA targeting viral transcripts, capsid assembly modulators, and approaches targeting the secretion of viral envelope proteins. Restoration of immune responses is a complementary approach. The restoration of innate immunity against HBV can be achieved, with TLR agonists or specific antiviral cytokine delivery. Restoration of adaptive immunity may be achieved with inhibitors of negative checkpoint regulators, therapeutic vaccines, or autologous transfer of engineered HBV-specific T cells. Novel targets and compounds will readily be evaluated using both relevant and novel in vitro and in vivo models of HBV infection. The addition of one or several new drugs to current therapies should offer the prospect of a markedly improved response to treatments and an increased rate of functional cure. This should lead to a reduced risk of antiviral drug resistance, and to a decreased incidence of cirrhosis and hepatocellular carcinoma (HCC).

  3. Antiviral therapy of hepatitis C as curative treatment of indolent B-cell lymphoma

    Science.gov (United States)

    Merli, Michele; Carli, Giuseppe; Arcaini, Luca; Visco, Carlo

    2016-01-01

    The association of hepatitis C virus (HCV) and B-cell non-Hodgkin lymphomas (NHL) has been highlighted by several epidemiological and biological insights; however the most convincing evidence is represented by interventional studies demonstrating the capability of antiviral treatment (AT) with interferon (IFN) with or without ribavirin to induce the regression of indolent lymphomas, especially of marginal-zone origin. In the largest published retrospective study (100 patients) the overall response rate (ORR) after first-line IFN-based AT was 77% (44% complete responses) and responses were sustainable (median duration of response 33 mo). These results were confirmed by a recent meta-analysis on 254 patients, demonstrating an ORR of 73%. Moreover this analysis confirmed the highly significant correlation between the achievement of viral eradication sustained virological response (SVR) and hematological responses. Two large prospective studies demonstrated that AT is associated with improved survival and argue in favor of current guidelines’ recommendation of AT as preferential first-line option in asymptomatic patients with HCV-associated indolent NHL. The recently approved direct-acting antiviral agents (DAAs) revolutionized the treatment of HCV infection, leading to SVR approaching 100% in all genotypes. Very preliminary data of IFN-free DAAs therapy in indolent HCV-positive NHL seem to confirm their activity in inducing lymphoma regression.

  4. ELIMINATION OF CVB ( FROM A RANGE OF CHRYSANTHEMUM VARIETIES BY APICAL MERISTEM CULTURE FOLLOWING ANTIVIRAL AGENT AND HEAT TREATMENTS

    Directory of Open Access Journals (Sweden)

    KURNIAWAN BUDIARTO

    2011-09-01

    Full Text Available CVB elimination for retaining healthy protocols from infected chrysanthemum plant wasinvestigated through combined treatment of meristem culture with synthetic antiviral ribavirinor thermotherapy under conditions. The biological materials used for the experimentconstituted of six commercial varieties: Dewi Sartika, Saraswati, Yellow Fiji, White Puma,Yellow Puma and White Reagent. Tissue culture initiation was conducted through plantletestablishment using MS supplemented with IAA. Ribavirin was added in media with theconcentration of 40 mg/l on cv. Dewi Sartika, Saraswati and Yellow Fiji. Parallel with this step,heat treatment with different durations (1, 2, and 3 weeks was also conducted on the plantletson White Puma, Yellow Puma and White Reagent. Meristem culture was done followingthe chemo- and thermotherapy. The experiment resumed the failure of single treatment ofmeristem culture in eliminating CVB from the infected chrysanthemum plantlets. Under heattreatment, percentage of virus-free plantlets increased along with the duration ofthermotherapy, though the survival rate of plantlets decreased in lengthened heat treatment.The best results regarding virus free plant percentage were obtained when meristem culture wasapplied following ribavirin or three weeks of heat treatment.

  5. Dynamic evolution of hepatitis C virus resistance-associated substitutions in the absence of antiviral treatment

    Science.gov (United States)

    Eltahla, Auda A.; Leung, Preston; Pirozyan, Mehdi R.; Rodrigo, Chaturaka; Grebely, Jason; Applegate, Tanya; Maher, Lisa; Luciani, Fabio; Lloyd, Andrew R.; Bull, Rowena A.

    2017-01-01

    Resistance against new hepatitis C virus (HCV) antivirals is an area of increasing interest. Resistance-associated substitutions (RASs) have been identified in treatment-naïve individuals, but pressures driving treatment-independent RAS emergence are poorly understood. We analysed the longitudinal evolution of RASs in twelve participants with early acute HCV infections. Full-genome deep sequences were analysed for changes in RAS frequency within NS3, NS5A and NS5B-coding regions over the course of the infection. Emergence of RASs relevant only to the polymerase non-nucleoside inhibitors (NNI) was detected, and these lay within CD8+ T-cell epitopes. Conversely, the loss of NNI RASs over time appeared likely to be driven by viral fitness constraints. These results highlight the importance of monitoring CD8+ T cell epitope-associated RASs in populations with dominant HLA types. PMID:28139734

  6. Bay laurel (Laurus nobilis) as potential antiviral treatment in naturally BQCV infected honeybees.

    Science.gov (United States)

    Aurori, Adriana C; Bobiş, Otilia; Dezmirean, Daniel S; Mărghitaş, Liviu A; Erler, Silvio

    2016-08-15

    Viral diseases are one of the multiple factors associated with honeybee colony losses. Apart from their innate immune system, including the RNAi machinery, honeybees can use secondary plant metabolites to reduce or fully cure pathogen infections. Here, we tested the antiviral potential of Laurus nobilis leaf ethanolic extracts on forager honeybees naturally infected with BQCV (Black queen cell virus). Total viral loads were reduced even at the lowest concentration tested (1mg/ml). Higher extract concentrations (≥5mg/ml) significantly reduced virus replication. Measuring vitellogenin gene expression as an indicator for transcript homeostasis revealed constant RNA levels before and after treatment, suggesting that its expression was not impacted by the L. nobilis treatment. In conclusion, plant secondary metabolites can reduce virus loads and virus replication in naturally infected honeybees.

  7. Application of Bayesian Approach to Cost-Effectiveness Analysis of Antiviral Treatments in Chronic Hepatitis B

    Science.gov (United States)

    Zhang, Hua; Huo, Mingdong; Chao, Jianqian; Liu, Pei

    2016-01-01

    Background Hepatitis B virus (HBV) infection is a major problem for public health; timely antiviral treatment can significantly prevent the progression of liver damage from HBV by slowing down or stopping the virus from reproducing. In the study we applied Bayesian approach to cost-effectiveness analysis, using Markov Chain Monte Carlo (MCMC) simulation methods for the relevant evidence input into the model to evaluate cost-effectiveness of entecavir (ETV) and lamivudine (LVD) therapy for chronic hepatitis B (CHB) in Jiangsu, China, thus providing information to the public health system in the CHB therapy. Methods Eight-stage Markov model was developed, a hypothetical cohort of 35-year-old HBeAg-positive patients with CHB was entered into the model. Treatment regimens were LVD100mg daily and ETV 0.5 mg daily. The transition parameters were derived either from systematic reviews of the literature or from previous economic studies. The outcome measures were life-years, quality-adjusted lifeyears (QALYs), and expected costs associated with the treatments and disease progression. For the Bayesian models all the analysis was implemented by using WinBUGS version 1.4. Results Expected cost, life expectancy, QALYs decreased with age. Cost-effectiveness increased with age. Expected cost of ETV was less than LVD, while life expectancy and QALYs were higher than that of LVD, ETV strategy was more cost-effective. Costs and benefits of the Monte Carlo simulation were very close to the results of exact form among the group, but standard deviation of each group indicated there was a big difference between individual patients. Conclusions Compared with lamivudine, entecavir is the more cost-effective option. CHB patients should accept antiviral treatment as soon as possible as the lower age the more cost-effective. Monte Carlo simulation obtained costs and effectiveness distribution, indicate our Markov model is of good robustness. PMID:27574976

  8. Health-related quality of life and impact of antiviral treatment in Chinese patients with chronic hepatitis C in Taiwan

    Institute of Scientific and Technical Information of China (English)

    Shih-Chao Kang; Shinn-Jang Hwang; Shiang-Ho Lee; Full-Young Chang; Shou-Dong Lee

    2005-01-01

    AIM: To evaluate health-related quality of life (HRQOL) in Chinese patients with chronic hepatitis C (CH-C), and the impact of antiviral treatment.METHODS: Short Form 36 (SF-36) Health-related Quality of Life Questionnaires to interview CH-C patients, and age- and sex-matched control subjects at outpatient clinics of a medical center in Taiwan were used. Data were transformed to scores for comparisons of eight major SF-36 domains. We also enrolled consecutive CH-C patients who completed one course of antiviral treatment(interferon α with ribavirin), and measured the HRQOLbefore, at the 12th wk of treatment, at the end of treatment, and at mo 6, after stopping the treatment to evaluate the impact of antiviral treatment.RESULTS: A total of 371 outpatients were enrolled, including 182 with CH-C and 189 age- and sex-matched subjects without CH-C. CH-C subjects had obviously lower educational status (P<0.01). Mean scores of domains in general health, physical functioning, role-physical,role-emotional, vitality, and mental health of the SF-36 were significantly lower in subjects with CH-C than those without CH-C (P<0.05). In an analysis of 47 CH-C patients who received and completed the whole course of antiviral treatment, mean scores of all domains were significantly lower at wk 12 of treatment compared to baseline. The scores returned to pretreatment values by the end of treatment, but were significantly increased at mo 6 after stopping the treatment. Among the 47 CH-C patients, 21 had sustained responses and 26 had nonsustained responses to antiviral treatment. Compared to pretreatment values, subjects with sustained responses had significantly lower social functioning scores at wk 12 of treatment, and scores for all SF-36 domains returned to pretreatment values, and increased significantly at mo 6 after stopping the treatment. For non-sustained virological responders, scores of all SF-36 domains significantly decreased at wk 12 of treatment, and did not increase

  9. Antiviral Efficacy and Host Innate Immunity Associated with SB 9200 Treatment in the Woodchuck Model of Chronic Hepatitis B

    Science.gov (United States)

    Korolowicz, Kyle E.; Iyer, Radhakrishnan P.; Czerwinski, Stefanie; Suresh, Manasa; Yang, Junming; Padmanabhan, Seetharamaiyer; Sheri, Anjaneyulu; Pandey, Rajendra K.; Skell, Jeffrey; Marquis, Judith K.; Kallakury, Bhaskar V.; Tucker, Robin D.; Menne, Stephan

    2016-01-01

    SB 9200, an oral prodrug of the dinucleotide SB 9000, is being developed for the treatment of chronic hepatitis B virus (HBV) infection and represents a novel class of antivirals. SB 9200 is thought to activate the viral sensor proteins, retinoic acid-inducible gene 1 (RIG-I) and nucleotide-binding oligomerization domain-containing protein 2 (NOD2) resulting in interferon (IFN) mediated antiviral immune responses in virus-infected cells. Additionally, the binding of SB 9200 to these sensor proteins could also sterically block the ability of the viral polymerase to access pre-genomic RNA for nucleic acid synthesis. The immune stimulating and direct antiviral properties of SB 9200 were evaluated in woodchucks chronically infected with woodchuck hepatitis virus (WHV) by daily, oral dosing at 15 and 30 mg/kg for 12 weeks. Prolonged treatment resulted in 2.2 and 3.7 log10 reductions in serum WHV DNA and in 0.5 and 1.6 log10 declines in serum WHV surface antigen from pretreatment level with the lower or higher dose of SB 9200, respectively. SB 9200 treatment also resulted in lower hepatic levels of WHV nucleic acids and antigen and reduced liver inflammation. Following treatment cessation, recrudescence of viral replication was observed but with dose-dependent delays in viral relapse. The antiviral effects were associated with dose-dependent and long-lasting induction of IFN-α, IFN-β and IFN-stimulated genes in blood and liver, which correlated with the prolonged activation of the RIG-I/NOD2 pathway and hepatic presence of elevated RIG-I protein levels. These results suggest that in addition to a direct antiviral activity, SB 9200 induces antiviral immunity during chronic hepadnaviral infection via activation of the viral sensor pathway. PMID:27552102

  10. Depletion of elongation initiation factor 4E binding proteins by CRISPR/Cas9 genome editing enhances antiviral response in porcine cells

    Science.gov (United States)

    Type I interferons (IFN) are key mediators of the innate antiviral response in mammalian cells. Elongation initiation factor 4E binding proteins (4E-BPs) are translational controllers of interferon regulatory factor 7 (IRF7), the master regulator of IFN transcription. The role of 4EBPs in the negat...

  11. Regulation of Eukaryotic Initiation Factor 4E and Its Isoform: Implications for Antiviral Strategy in Plants

    Institute of Scientific and Technical Information of China (English)

    Yu-Yang Zhang; Han-Xia Li; Bo Ou-yang; Zhi-Biao Ye

    2006-01-01

    In recent years, biotechnology has permitted regulation of the expression of endogenous plant genes to improve agronomicaiiy important traits. Genetic modification of crops has benefited from emerging knowledge of new genes, especially genes that exhibit novel functions, one of which is eukaryotic initiation factor 4E (elF4E). elF4E is one of the most important translation initiation factors involved in eukaryotic initiation. Recent research has demonstrated that virus resistance mediated by elF4E and its isoform elF (iso)4E occurs in several plant-virus interactions, thus indicating a potential new role for elF4E/elL(iso)4E in resistance strategies against plant viruses. In this review, we briefly describe elF4E activity in plant translation, its potential role, and functions of the elF4E subfamily in plant-virus interactions. Other initiation factors such as elF4G could also play a role in plant resistance against viruses. Finally, the potential for developing elF4E-medlated resistance to plant viruses in the future is discussed. Future research should focus on elucidation of the resistance mechanism and spectrum mediated by elF4E. Knowledge of a particular plant-virus interaction will help to deepen our understanding of elF4E and other eukaryotic initiation factors, and their involvement in virus disease control.

  12. Direct antiviral agent treatment of decompensated hepatitis C virus-induced liver cirrhosis

    Institute of Scientific and Technical Information of China (English)

    Shogo; Ohkoshi; Haruka; Hirono; Satoshi; Yamagiwa

    2015-01-01

    Recently, direct antiviral agents(DAAs) have been increasingly used for the treatment of chronic hepatitis C virus(HCV) infections, replacing interferon-based regimens that have severe adverse effects and low tolerability. The constant supply of new DAAs makes shorter treatment periods with enhanced safety possible. The efficacy of DAAs for treatment of compensated liver cirrhosis(LC) is not less than that for treatment of non-cirrhotic conditions. These clinical advantages have been useful in pre- and post-liver transplantation(LT) settings. Moreover, DAAs can be used to treat decompensated HCV-induced LC in elderly patients or those with severe complications otherwise having poor prognosis. Although encouraging clinical data are beginning to appear, the actual efficacy of DAAs for suppressing disease progression, allowing delisting for LT and, most importantly, improving prognosis of patients with decompensated HCV-LC remains unknown. Casecontrol studies to examine the short- or long-term effects of DAAs for treatment of decompensated HCV-LC are urgently need.

  13. Efficient Suppression of Hepatitis C Virus Replication by Combination Treatment with miR-122 Antagonism and Direct-acting Antivirals in Cell Culture Systems

    OpenAIRE

    Fanwei Liu; Tetsuro Shimakami; Kazuhisa Murai; Takayoshi Shirasaki; Masaya Funaki; Masao Honda; Seishi Murakami; Minkyung Yi; Hong Tang; Shuichi Kaneko

    2016-01-01

    Direct-acting antivirals (DAAs) against Hepatitis C virus (HCV) show effective antiviral activity with few side effects. However, the selection of DAA-resistance mutants is a growing problem that needs to be resolved. In contrast, miR-122 antagonism shows extensive antiviral effects among all HCV genotypes and a high barrier to drug resistance. In the present study, we evaluated three DAAs (simeprevir, daclatasvir, and sofosbuvir) in combination with anti-miR-122 treatment against HCV genotyp...

  14. Some Preliminary Results on an SEIARD Epidemic Model with Vaccination and Antiviral Treatment Controls and Dead-Infective Culling Action

    Science.gov (United States)

    De la Sen, M.; Nistal, R.; Alonso-Quesada, S.; Garrido, A. J.

    2016-08-01

    This paper studies the non-negativity and stability properties of the solutions of a newly proposed SEIADR model which incorporates asymptomatic and dead-infective subpopulations to those defining the standard SEIR model and, in parallel, it incorporates feedback vaccination and antiviral treatment controls.

  15. Antiviral drug valacyclovir treatment combined with a clean feeding system enhances the suppression of salivary gland hypertrophy in laboratory colonies of Glossina pallidipes

    Science.gov (United States)

    2014-01-01

    Background Hytrosaviridae cause salivary gland hypertrophy (SGH) syndrome in some infected tsetse flies (Diptera: Glossinidae). Infected male and female G. pallidipes with SGH have a reduced fecundity and fertility. Due to the deleterious impact of the virus on G. pallidipes colonies, adding the antiviral drug valacyclovir to the blood diet and changing the feeding regime to a clean feeding system (each fly receives for each feeding a fresh clean blood meal) have been investigated to develop virus management strategies. Although both approaches used alone successfully reduced the virus load and the SGH prevalence in small experimental groups, considerable time was needed to obtain the desired SGH reduction and both systems were only demonstrated with colonies that had a low initial virus prevalence (SGH ≤ 10%). As problems with SGH are often only recognized once the incidence is already high, it was necessary to demonstrate that this combination would also work for high prevalence colonies. Findings Combining both methods at colony level successfully suppressed the SGH in G. pallidipes colonies that had a high initial virus prevalence (average SGH of 24%). Six months after starting the combined treatment SGH symptoms were eliminated from the treated colony, in contrast to 28 months required to obtain the same results using clean feeding alone and 21 months using antiviral drug alone. Conclusions Combining valacyclovir treatment with the clean feeding system provides faster control of SGH in tsetse than either method alone and is effective even when the initial SGH prevalence is high. PMID:24886248

  16. Antiviral Treatment Alters the Frequency of Activating and Inhibitory Receptor-Expressing Natural Killer Cells in Chronic Hepatitis B Virus Infected Patients

    Directory of Open Access Journals (Sweden)

    Juan Lv

    2012-01-01

    Full Text Available Natural killer (NK cells play a critical role in innate antiviral immunity, but little is known about the impact of antiviral therapy on the frequency of NK cell subsets. To this aim, we performed this longitudinal study to examine the dynamic changes of the frequency of different subsets of NK cells in CHB patients after initiation of tenofovir or adefovir therapy. We found that NK cell numbers and subset distribution differ between CHB patients and normal subjects; furthermore, the association was found between ALT level and CD158b+ NK cell in HBV patients. In tenofovir group, the frequency of NK cells increased during the treatment accompanied by downregulated expression of NKG2A and KIR2DL3. In adefovir group, NK cell numbers did not differ during the treatment, but also accompanied by downregulated expression of NKG2A and KIR2DL3. Our results demonstrate that treatment with tenofovir leads to viral load reduction, and correlated with NK cell frequencies in peripheral blood of chronic hepatitis B virus infection. In addition, treatments with both tenofovir and adefovir in chronic HBV infected patients induce a decrease of the frequency of inhibitory receptor+ NK cells, which may account for the partial restoration of the function of NK cells in peripheral blood following treatment.

  17. The value of some genetic factors for prediction of chronic hepatitis C antiviral treatment effectiveness

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    V. M. Mitsura

    2014-01-01

    Full Text Available Aim: To determine the value of gene polymorphisms of interleukin-28B (IL28B, RNase L, HLA DRB1*1101 and HLADQB1*03 alleles as predictors of antiviral treatment efficacy in patients with chronic hepatitis C (CHC.Material and methods. A total of 156 in-patients with chronic hepatitis C (65.4% men, 62.4% had genotype 1 hepatitis C virus – HCV were studied. The results of treatment with interferon (IFN and ribavirin (RBV were analyzed in 74 patients. Polymerase chain reaction identified single nucleotide polymorphisms (SNP of the gene IL28B 39743165T>G (rs8099917, SNP 39738787C> T (rs12979860, RNase L gene (1385G>A, HLA DRB1*1101 and HLA-DQB1*03 alleles.Results. In patients with HCV genotype 1 mutant alleles were more common in SNP 39743165T>G (p=0.001 and 39738787C>T (p=0.0002 than in patients with other genotypes. Response to therapy IFN/RBV was higher in those with “favorable” TT variant (SNP 39743165T>G and CC (SNP 39738787C>T, in those with their combination virologic response ffect were found according to genes IL28B and RNase L SNP variants, DRB1*1101 and HLA-DQB1*03 alleles.Conclusion. Testing for SNP 39738787C>T of IL28B gene is recommended before starting therapy IFN / RBV for all patients with genotype 1 HCV as a predictor of treatment response. Testing SNP 1385G>A gene RNase L and DRB1*1101, HLA-DQB1*03 alleles has no apparent prognostic value for patients with CHC antiviral therapy.

  18. Treatment of hepatitis C virus genotype 3 infection with direct-acting antiviral agents

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    L.P. Zanaga

    Full Text Available Hepatitis C virus (HCV genotype 3 is responsible for 30.1% of chronic hepatitis C infection cases worldwide. In the era of direct-acting antivirals, these patients have become one of the most challenging to treat, due to fewer effective drug options, higher risk of developing cirrhosis and hepatocellular carcinoma and lower sustained virological response (SVR rates. Currently there are 4 recommended drugs for the treatment of HCV genotype 3: pegylated interferon (PegIFN, sofosbuvir (SOF, daclatasvir (DCV and ribavirin (RBV. Treatment with PegIFN, SOF and RBV for 12 weeks has an overall SVR rate of 83–100%, without significant differences among cirrhotic and non-cirrhotic patients. However, this therapeutic regimen has several contraindications and can cause significant adverse events, which can reduce adherence and impair SVR rates. SOF plus RBV for 24 weeks is another treatment option, with SVR rates of 82–96% among patients without cirrhosis and 62–92% among those with cirrhosis. Finally, SOF plus DCV provides 94–97% SVR rates in non-cirrhotic patients, but 59–69% in those with cirrhosis. The addition of RBV to the regimen of SOF plus DCV increases the SVR rates in cirrhotic patients above 80%, and extending treatment to 24 weeks raises SVR to 90%. The ideal duration of therapy is still under investigation. For cirrhotic patients, the optimal duration, or even the best regimen, is still uncertain. Further studies are necessary to clarify the best regimen to treat HCV genotype 3 infection.

  19. Measuring the Response of Extrahepatic Symptoms and Quality of Life to Antiviral Treatment in Patients with Hepatitis C

    Directory of Open Access Journals (Sweden)

    David Isaacs

    2013-01-01

    Full Text Available Background. HCV infection is associated with musculoskeletal manifestations such as chronic widespread pain, sicca syndrome, polyarthritis, and a reduced HRQOL. Little data is available on the effect of treatment on these manifestations. This study measured changes in extrahepatic symptoms and HRQOL before and after antiviral treatment in a large UK patient cohort. Methods. 118 patients completed HQLQ and rheumatological questionnaires before and after treatment with pegylated interferon-α and ribavirin, with specific regard to chronic widespread pain, sicca syndrome, and sustained virological response. Results. There was significant improvement in HQLQ domains of physical functioning, physical disability, social functioning, limitations and health distress due to hepatitis, and general health. There was significant deterioration in domains of positive well-being, health distress, and mental health. There was a significant decline prevalence of CWP (26.3% versus 15.3%, . Sicca syndrome prevalence fell insignificantly (12.7% versus 11%. SVR was associated positively with all HRQOL changes and significantly with CWP remission. Conclusions. HCV antivirals significantly improve poor HRQOL scores and CWP. Before treatment, both were common, coassociated, and unaccounted for through mixed cryoglobulinemia alone. Although a role of the hepatitis C virus in CWP cannot be deduced by these results, symptomatic improvement via antiviral treatment exists for this subset of patients.

  20. Direct-Acting Antivirals for the Treatment of Chronic Hepatitis C: Open Issues and Future Perspectives

    Directory of Open Access Journals (Sweden)

    Hee Bok Chae

    2013-01-01

    Full Text Available Currently, two direct-acting antivirals (DAAs show well-established efficacy against hepatitis C virus (HCV, namely, first-wave protease inhibitors telaprevir and boceprevir. Most clinical trials have examined DAAs in combination with standard of care (SOC regimens. Future therapeutic drugs were divided into three categories. They are second-wave protease inhibitors, second-generation protease inhibitors, and polymerase inhibitors. Second-wave protease inhibitors are more improved form and can be administered once a day. Oral drug combinations can be favored because interferon (IFN not only has to be given as intradermal injection, but also can cause several serious side effects. Combination of drugs with different mechanisms shows a good sustained virological response (SVR. But several mutations are associated with viral resistance to DAAs. Therefore, genotypic resistance data may provide insights into strategies aimed at maximizing SVR rates and minimizing resistance. Combined drug regimens are necessary to prevent the emergence of drug-resistant HCV. Many promising DAA candidates have been identified. Of these, a triple regimen containing sofosbuvir shows promise, and treatment with daclatasvir plus asunaprevir yields a high SVR rate (95%. Oral drug combinations will be standard of care in the near future.

  1. Antiviral treatment of hepatitis B virus-transgenic mice by a marine organism, Styela plicata

    Institute of Scientific and Technical Information of China (English)

    Rui Wang; Zhen-Lan Du; Wen-Jun Duan; Xin Zhang; Fan-Lin Zeng; Xin-Xiang Wan

    2006-01-01

    AIM: To evaluate the antiviral effect of the effective ingredient of Styela plicata in a murine model of hepatitis B virus carrier.METHODS: HBV-transgenic mice were divided into 3 groups (control group, lamivudine treatment group and the effective ingredient of Styela plicata treatment group) and assigned to receive normal diet, lamivudine or the effective ingredient of Styela plicata for consecutive weeks. Serum hepatitis B surface antigen was detected by enzyme-linked immunosorbent assay (ELISA) method. Serum HBV DNA was detected by real-time polymerase chain reaction (RT-PCR). Serum T helper (h) 1 cytokine interleukin (IL)-2 and Th2 cytokine IL-6 were detected by the quantitative sandwich enzyme immunoassay technique. Another group of HBV-transgenic mice was assigned to receive the effective ingredient of Styela plicata for consecutive weeks. The histology of liver tissue was evaluated before and after treatment.RESULTS: Twelve weeks after starting the therapy, serum hepatitis B surface antigen was significantly lowered in Styela plicata -treated mice and lamivudine-treated mice compared with the mice receiving normal diet (F12wk = 88.81, P12wk = 0.000 < 0.01). Serum HBV DNA was significantly lowered in Styela plicata -treated mice and lamivudine-treated mice compared with the mice receiving normal diet (F12wk = 20.71, P12wk = 0.000 < 0.01). However, like lamivudine, the effective ingredient of Styela plicata could not inhibit the replication of HBV completely. A rebound phenomenon of hepatitis B sur-face antigen and HBV DNA in sera could be found 4 wk after withdrawal of medication. Eight weeks after starting the therapy, serum levels before and after Styela plicata treatment of IL-2 were 2.41 ± 0.38 and 10.56 ± 0.78 ng/L, respectively (t8wk = -16.51, P8wk = 0.000 < 0.01).Compared with the serum levels of IL-2 in the normal diet-treated mice (2.48 ± 0.17 ng/L; t8wk = 13.23, P8wk = 0.000 < 0.01). Serum levels before and after Styela plicata treatment

  2. Report of the first Asia-Pacific Forum on antiviral treatment of influenza, Asia-Pacific Alliance for the Control of Influenza, Bangkok, 14 June 2012.

    Science.gov (United States)

    Jennings, Lance C; Smith, David W; Chan, Paul K S

    2013-11-01

    On 14 June 2012, the Asia-Pacific Alliance for the Control of Influenza (APACI) convened the first Antiviral Forum jointly with the Influenza Foundation of Thailand and the Thailand Department of Disease Control. The goals of the meeting were to improve pandemic planning in the region from lessons learned during the 2009 pandemic, particularly with regard to the safety and efficacy of antiviral use; gain a better understanding of the therapeutic use of antivirals in seasonal influenza; review and analyse the official influenza control policies of Asia-Pacific countries and evidence gaps to support policy development; and to establish collaborative relationships to promote best practices in the use of antivirals for the treatment of influenza. The urgent need for education highlighting the importance of influenza and the benefits of antiviral drug use in the Asia-Pacific region was identified.

  3. Vaccination and antiviral treatment of neglected diseases caused by flaviviral infections.

    Science.gov (United States)

    Schleich, K; Nürnberger, C; Sobanski, A; Efferth, T

    2011-01-01

    Flaviviral infections have a re-emerging impact on the health situation in developing countries with several billions of people living at risk. In the present review, we focus on three members of the genus Flavivirus belonging to the Flaviviridae family. They are transmitted to humans by mosquito bites, namely those viruses leading to Dengue Fever, Yellow Fever and mosquito-borne Japanese encephalitis. All three virus groups have a spherical structure with a diameter of approximately 50 nm. Although sharing a similar genomic structure and intracellular life cycle, they show different clinical manifestations. Infections are incurable, as there is no antiviral treatment available for either of the three viruses. Thus, prevention and vaccination are the best defenses. The most promising vaccines are live attenuated vaccines (LAVs), such as the YF17D strain against Yellow Fever or the SA-14-14-2 strain against Japanese encephalitis. Additionally, recombinant vaccines for Japanese encephalitis are in development. Although Dengue Fever is the most prevalent arthropode-borne flaviviral infection and a lot of research to develop a vaccine against all four Dengue Fever serotypes was undertaken, no vaccine is available on the market yet. Promising tetravalent vaccine candidates are currently undergoing clinical phase trials, including LAVs, recombinant and chimeric candidates as well as non-replicating vaccine approaches. Additionally, encouraging anti-flaviviral approaches target non-structural proteins, virus-specific proteases essential for cellular maturation of viral particles. Peptide inhibitors against the highly conserved NS2B and NS3 proteases are attractive as pan-flaviviral drug candidates.

  4. Antiviral Efficacy and Host Immune Response Induction during Sequential Treatment with SB 9200 Followed by Entecavir in Woodchucks.

    Science.gov (United States)

    Suresh, Manasa; Korolowicz, Kyle E; Balarezo, Maria; Iyer, Radhakrishnan P; Padmanabhan, Seetharamaiyer; Cleary, Dillon; Gimi, Rayomand; Sheri, Anjaneyulu; Yon, Changsuek; Kallakury, Bhaskar V; Tucker, Robin D; Afdhal, Nezam; Menne, Stephan

    2017-01-01

    SB 9200, an orally bioavailable dinucleotide, activates the viral sensor proteins, retinoic acid-inducible gene 1 (RIG-I) and nucleotide-binding oligomerization domain-containing protein 2 (NOD2) causing the induction of the interferon (IFN) signaling cascade for antiviral defense. The present study evaluated the overall antiviral response in woodchucks upon induction of immune response, first with SB 9200 followed by Entecavir (ETV) versus reduction of viral burden with ETV followed by SB 9200 immunomodulation. Woodchucks chronically infected with woodchuck hepatitis virus (WHV) were treated orally with SB 9200 (30 mg/kg/day) and ETV (0.5 mg/kg/day). Group 1 received ETV for 4 weeks followed by SB 9200 for 12 weeks. Group 2 received SB 9200 for 12 weeks followed by ETV for 4 weeks. At the end of treatment in Group 2, average reductions of 6.4 log10 in serum WHV DNA and 3.3 log10 in WHV surface antigen were observed whereas in Group 1, average reductions of 4.2 log10 and 1.1 log10 in viremia and antigenemia were noted. Both groups demonstrated marked reductions in hepatic WHV nucleic acid levels which were more pronounced in Group 2. Following treatment cessation and the 8-week follow-up, recrudescence of viral replication was observed in Group 1 while viral relapse in Group 2 was significantly delayed. The antiviral effects observed in both groups were associated with temporally different induction of IFN-α, IFN-β, and IFN-stimulated genes in blood and liver. These results suggest that the induction of host immune responses by pretreatment with SB 9200 followed by ETV resulted in antiviral efficacy that was superior to that obtained using the strategy of viral reduction with ETV followed by immunomodulation.

  5. the denver tube Combined with antiviral drugs In the treatment of HBV-related Cirrhosis with Refractory ascites:a Report of three Cases

    Institute of Scientific and Technical Information of China (English)

    Xiao-jin Wang; Li-qin Shi; Qing-chun Fu; Liu-da Ni; Feng Zhou; Jin-wei Chen; Cheng-wei Chen

    2014-01-01

    Treatment of nucleos(t)ide antiviral drugs for decompensated HBV-related cirrhosis can signiifcantly improve the prognosis. But those patients with refractory ascites possibly deteriorate due to the complications of ascites before any beneift from anti-viral drugs could be observed. Therefore, it is important to ifnd a way to help the patients with HBV-related cirrhosis and refractory ascites to receive the full beneifts from antiviral therapy. Peritoneovenous shunt (PVS) using Denver tube enables ascites to continuously bypass into systemic circulation, thereby reducing ascites and albumin input and improving quality of life. We report herein 3 cases of decompensated HBV-related cirrhosis with refractory ascites, PVS using Denver tube was combined with lamivudine for antiviral treatment before and after. Then, ascites was alleviated significantly or disapeared and viral responsed well. All patients achieved a satisfactory long-term survival from 6.7 to 14.7 years. It was suggested that the Denver shunt could be used as an adjuvant method to antiviral drugs for decompensated HBV-related cirrhosis with refractory ascites to help the patients reap the full beneifts and maximize efifcacy of antiviral treatment.

  6. New antiviral agents and new treatments on the horizon for the management of viral hepatitis

    Directory of Open Access Journals (Sweden)

    M. Sönmezoğlu

    2011-12-01

    Full Text Available Transfusion dependant patients are at risk of acquiring transfusiontransmitted viral infections including Hepatitis B virus (HBV and Hepatitis C (HCV. These infections can lead to cirrhosis and hepatic cancer. Standard treatment, although with improved therapeutic results still exhibits resistance and relapses. New antiviral agents have been developed to further improve results and reduce adverse events. For hepatitis B, along with pegylated interferon a-2a, other drugs that have been approved include lamivudine, adefovir, entecavir, telbivudine and tenofovir, while emtricitabine and clevudine are awaiting FDA approval. Possible combination drug therapy may improve efficacy without engendering resistance. For hepatitis C, standard therapy has been the combination of Peg-IFN/Ribavarin. Genotype 1 of the virus, which is widespread in the USA and Europe, can be resistant to treatment especially with high viral load. Directly acting antiviral agents (DAAs, are being developed. These are: i HCV NS3 protease inhibitors, such as telaprevir and boceprevir, which are currently approved by the FDA. Several other compounds are in phase I-II development; ii NS5B polymerase inhibitors, which target HCV replication. These include mericitabine (a nucleoside analogue inhibitor currently in phase III trials, and nonnucleiside inhibitors; iii New intreferons such as pgylated interferonl, which are also on trial. Triple therapy using pegylated IFNa/ Ribavarin along with telaprevir or boceprevir are also under trial. 输血依赖型患者面临输血传播病毒感染的风险,包括乙型肝炎病毒(HBV)和丙型肝炎病毒(HCV)。 这些感染可导致肝硬化和肝癌。 标准治疗,尽管具有改善的治疗效果,但是仍然表现出抗病性和复发性 已研发出新的抗病毒药物,进一步完善结果和降低不良事件。 关于乙型肝炎,和聚乙二醇化干扰素a-2a一起,其他已获批准的药物包括拉米夫

  7. Herpes simplex virus keratitis: an update of the pathogenesis and current treatment with oral and topical antiviral agents.

    Science.gov (United States)

    Tsatsos, Michael; MacGregor, Cheryl; Athanasiadis, Ioannis; Moschos, Marilita M; Hossain, Parwez; Anderson, David

    2016-12-01

    Ophthalmic herpes simplex viral keratitis is responsible for a range of ocular manifestations from superficial epithelial disease to stromal keratitis and endotheliitis. The Herpetic Eye Disease Study has guided the management of herpetic eye disease for almost twenty years, but newer medications such as valacyclovir are now available and are considered to have better bioavailability than acyclovir. In this review, we examine the existing evidence on the pathogenesis of different ophthalmic herpes simplex viral keratitis disease modalities and the role of oral and topically administered antiviral drugs in the treatment of herpes simplex viral keratitis.

  8. Ultrasensitive HCV RNA Quantification in Antiviral Triple Therapy: New Insight on Viral Clearance Dynamics and Treatment Outcome Predictors

    Science.gov (United States)

    Garbuglia, Anna Rosa; Visco-Comandini, Ubaldo; Lionetti, Raffaella; Lapa, Daniele; Castiglione, Filippo; D’Offizi, Gianpiero; Taibi, Chiara; Montalbano, Marzia; Capobianchi, Maria Rosaria; Paci, Paola

    2016-01-01

    Objectives Identifying the predictive factors of Sustained Virological Response (SVR) represents an important challenge in new interferon-based DAA therapies. Here, we analyzed the kinetics of antiviral response associated with a triple drug regimen, and the association between negative residual viral load at different time points during treatment. Methods Twenty-three HCV genotype 1 (GT 1a n = 11; GT1b n = 12) infected patients were included in the study. Linear Discriminant Analysis (LDA) was used to establish possible association between HCV RNA values at days 1 and 4 from start of therapy and SVR. Principal component analysis (PCA) was applied to analyze the correlation between HCV RNA slope and SVR. A ultrasensitive (US) method was established to measure the residual HCV viral load in those samples which resulted “detected <12IU/ml” or undetectable with ABBOTT standard assay, and was retrospectively used on samples collected at different time points to establish its predictive power for SVR. Results According to LDA, there was no association between SVR and viral kinetics neither at time points earlier than 1 week (days 1 and 4) after therapy initiation nor later. The slopes were not relevant for classifying patients as SVR or no-SVR. No significant differences were observed in the median HCV RNA values at T0 among SVR and no-SVR patients. HCV RNA values with US protocol (LOD 1.2 IU/ml) after 1 month of therapy were considered; the area under the ROC curve was 0.70. Overall, PPV and NPV of undetectable HCV RNA with the US method for SVR was 100% and 46.7%, respectively; sensitivity and specificity were 38.4% and 100% respectively. Conclusion HCV RNA “not detected” by the US method after 1 month of treatment is predictive of SVR in first generation Protease inhibitor (PI)-based triple therapy. The US method could have clinical utility for advanced monitoring of virological response in new interferon based DAA combination regimens. PMID:27560794

  9. Whole genome HBV deletion profiles and the accumulation of preS deletion mutant during antiviral treatment

    Directory of Open Access Journals (Sweden)

    Zhang Dake

    2012-12-01

    Full Text Available Abstract Background Hepatitis B virus (HBV, because of its error-prone viral polymerase, has a high mutation rate leading to widespread substitutions, deletions, and insertions in the HBV genome. Deletions may significantly change viral biological features complicating the progression of liver diseases. However, the clinical conditions correlating to the accumulation of deleted mutants remain unclear. In this study, we explored HBV deletion patterns and their association with disease status and antiviral treatment by performing whole genome sequencing on samples from 51 hepatitis B patients and by monitoring changes in deletion variants during treatment. Clone sequencing was used to analyze preS regions in another cohort of 52 patients. Results Among the core, preS, and basic core promoter (BCP deletion hotspots, we identified preS to have the highest frequency and the most complex deletion pattern using whole genome sequencing. Further clone sequencing analysis on preS identified 70 deletions which were classified into 4 types, the most common being preS2. Also, in contrast to the core and BCP regions, most preS deletions were in-frame. Most deletions interrupted viral surface epitopes, and are possibly involved in evading immuno-surveillance. Among various clinical factors examined, logistic regression showed that antiviral medication affected the accumulation of deletion mutants (OR = 6.81, 95% CI = 1.296 ~ 35.817, P = 0.023. In chronic carriers of the virus, and individuals with chronic hepatitis, the deletion rate was significantly higher in the antiviral treatment group (Fisher exact test, P = 0.007. Particularly, preS2 deletions were associated with the usage of nucleos(tide analog therapy (Fisher exact test, P = 0.023. Dynamic increases in preS1 or preS2 deletions were also observed in quasispecies from samples taken from patients before and after three months of ADV therapy. In vitro experiments demonstrated that

  10. Estimating the Impact of Expanding Treatment Coverage and Allocation Strategies for Chronic Hepatitis C in a Direct Antiviral Agent Era

    Science.gov (United States)

    Poovorawan, Kittiyod; Pan-ngum, Wirichada; White, Lisa J.; Soonthornworasiri, Ngamphol; Wilairatana, Polrat; Wasitthankasem, Rujipat; Tangkijvanich, Pisit; Poovorawan, Yong

    2016-01-01

    Hepatitis C virus (HCV) infection is an important worldwide public health problem, and most of the global HCV burden is in low- to middle-income countries. This study aimed to estimate the future burden of chronic hepatitis C (CHC) and the impact of public health policies using novel antiviral agents in Thailand. A mathematical model of CHC transmission dynamics was constructed to examine the disease burden over the next 20 years using different treatment strategies. We compared and evaluated the current treatment (PEGylated interferon and ribavirin) with new treatments using novel direct-acting antiviral agents among various treatment policies. Thailand’s CHC prevalence was estimated to decrease 1.09%–0.19% in 2015–2035. Expanding treatment coverage (i.e., a five-fold increment in treatment accessibility) was estimated to decrease cumulative deaths (33,007 deaths avoided, 25.5% reduction) from CHC-related decompensated cirrhosis and hepatocellular carcinoma (HCC). The yearly incidence of HCC-associated HCV was estimated to decrease from 2,305 to 1,877 cases yearly with expanding treatment coverage. A generalized treatment scenario (i.e., an equal proportional distribution of available treatment to individuals at all disease stages according to the number of cases at each stage) was predicted to further reduce death from HCC (9,170 deaths avoided, 11.3% reduction) and the annual incidence of HCC (i.e., a further decrease from 1,877 to 1,168 cases yearly, 37.7% reduction), but cumulative deaths were predicted to increase (by 3,626 deaths, 3.7% increase). Based on the extensive coverage scenario and the generalized treatment scenario, we estimated near-zero death from decompensated cirrhosis in 2031. In conclusion, CHC-related morbidity and mortality in Thailand are estimated to decrease dramatically over the next 20 years. Treatment coverage and allocation strategies are important factors that affect the future burden of CHC in resource-limited countries like

  11. Optimal control of hepatitis C antiviral treatment programme delivery for prevention amongst a population of injecting drug users.

    Directory of Open Access Journals (Sweden)

    Natasha K Martin

    Full Text Available In most developed countries, HCV is primarily transmitted by injecting drug users (IDUs. HCV antiviral treatment is effective, and deemed cost-effective for those with no re-infection risk. However, few active IDUs are currently treated. Previous modelling studies have shown antiviral treatment for active IDUs could reduce HCV prevalence, and there is emerging interest in developing targeted IDU treatment programmes. However, the optimal timing and scale-up of treatment is unknown, given the real-world constraints commonly existing for health programmes. We explore how the optimal programme is affected by a variety of policy objectives, budget constraints, and prevalence settings. We develop a model of HCV transmission and treatment amongst active IDUs, determine the optimal treatment programme strategy over 10 years for two baseline chronic HCV prevalence scenarios (30% and 45%, a range of maximum annual budgets (£50,000-300,000 per 1,000 IDUs, and a variety of objectives: minimising health service costs and health utility losses; minimising prevalence at 10 years; minimising health service costs and health utility losses with a final time prevalence target; minimising health service costs with a final time prevalence target but neglecting health utility losses. The largest programme allowed for a given budget is the programme which minimises both prevalence at 10 years, and HCV health utility loss and heath service costs, with higher budgets resulting in greater cost-effectiveness (measured by cost per QALY gained compared to no treatment. However, if the objective is to achieve a 20% relative prevalence reduction at 10 years, while minimising both health service costs and losses in health utility, the optimal treatment strategy is an immediate expansion of coverage over 5-8 years, and is less cost-effective. By contrast, if the objective is only to minimise costs to the health service while attaining the 20% prevalence reduction, the

  12. Comparative proteomic analysis of growth hormone secretagogue A233 treatment of murine macrophage cells J774A.2 indicates it has a role in antiviral innate response

    Directory of Open Access Journals (Sweden)

    Rebeca Martínez

    2016-03-01

    General Significance: The increase of IFN-γ level and the differential modulation of antiviral proteins by the A233 peptide suggest that the molecule could activate an innate immune response with a possible further impact in the treatment of acute and chronic diseases.

  13. High Serum Lipopolysaccharide-Binding Protein Level in Chronic Hepatitis C Viral Infection Is Reduced by Anti-Viral Treatments

    Science.gov (United States)

    Nien, Hsiao-Ching; Hsu, Shih-Jer; Su, Tung-Hung; Yang, Po-Jen; Sheu, Jin-Chuan; Wang, Jin-Town; Chow, Lu-Ping; Chen, Chi-Ling

    2017-01-01

    Background Lipopolysaccharide-binding protein (LBP) has been reported to associate with metabolic diseases, such as obesity, diabetes, and non-alcoholic fatty liver disease. Since chronic hepatitis C virus (HCV) infection is associated with metabolic derangements, the relationship between LBP and HCV deserves additional studies. This study aimed to determine the serum LBP level in subjects with or without HCV infection and investigate the change of its level after anti-viral treatments with or without interferon. Methods and Findings We recruited 120 non-HCV subjects, 42 and 17 HCV-infected subjects respectively treated with peginterferon α-2a/ribavirin and direct-acting antiviral drugs. Basic information, clinical data, serum LBP level and abdominal ultrasonography were collected. All the subjects provided written informed consent before being enrolled approved by the Research Ethics Committee of the National Taiwan University Hospital. Serum LBP level was significantly higher in HCV-infected subjects than non-HCV subjects (31.0 ± 8.8 versus 20.0 ± 6.4 μg/mL; p-value < 0.001). After multivariate analyses, LBP at baseline was independently associated with body mass index, hemoglobin A1c, alanine aminotransferase (ALT) and HCV infection. Moreover, the baseline LBP was only significantly positively associated with ALT and inversely with fatty liver in HCV-infected subjects. The LBP level significantly decreased at sustained virologic response (27.4 ± 6.6 versus 34.6 ± 7.3 μg/mL, p-value < 0.001; 15.9 ± 4.4 versus 22.2 ± 5.7 μg/mL, p-value = 0.001), regardless of interferon-based or -free therapy. Conclusions LBP, an endotoxemia associated protein might be used as an inflammatory biomarker of both infectious and non-infectious origins in HCV-infected subjects. PMID:28107471

  14. Second-generation direct-acting-antiviral hepatitis C virus treatment: Efficacy, safety, and predictors of SVR12

    Science.gov (United States)

    Werner, Christoph R; Schwarz, Julia M; Egetemeyr, Daniel P; Beck, Robert; Malek, Nisar P; Lauer, Ulrich M; Berg, Christoph P

    2016-01-01

    AIM To gather data on the antiviral efficacy and safety of second generation direct acting antiviral (DAA) treatment with respect to sustained virological response (SVR) 12 wk after conclusion of treatment, and to determine predictors of SVR12 in this setting. METHODS Two hundred and sixty patients treated with SOF combination partners PR (n = 51), R (n = 10), SMV (n = 30), DCV (n = 81), LDV (n = 73), or 3D (n = 15). 144/260 were pre-treated, 89/260 had liver cirrhosis, 56/260 had portal hypertension with platelets < 100/nL, 25/260 had a MELD score ≥ 10 and 17/260 were post-liver transplantation patients. 194/260 had HCV GT1, 44/260 HCV GT3. RESULTS Two hundred and forty/256 (93.7%) patients achieved SVR12 (mITT); 4/260 were lost to follow-up. SVR12 rates for subgroups were: 92% for SOF/DCV, 93% for each SOF/SMV, SOF/PR, 94% for SOF/LDV, 100% for 3D, 94% for pretreated, 87% for liver cirrhosis, 82% for patients with platelets < 100/nL, 88% post-liver transplantation, 95% for GT1a, 93% for GT1b, 90% for GT3, 100% for GT2, 4, and 6. 12 patients suffered from relapse, 6 prematurely discontinued treatment, of which 4 died. Negative predictors of SVR12 were a platelet count < 100/nL, MELD score ≥ 10 (P < 0.0001), liver cirrhosis (P = 0.005) at baseline. In Interferon-free treatment GT3 had significantly lower SVR rates than GT1 (P = 0.016). Side effects were mild. CONCLUSION Excellent SVR12 rates and the favorable side-effect profile of DAA-combination therapy can be well translated into “real-world”. Patients with advanced liver disease, signs of portal hypertension, especially with platelets < 100/nL and patients with GT3 are in special need for further research efforts to overcome comparatively higher rates of virological failure. PMID:27672299

  15. Hepatitis C infected patients need vitamin D3 supplementation in the era of direct acting antivirals treatment

    Science.gov (United States)

    Kondo, Yasuteru

    2017-01-01

    It has been reported that the serum level of vitamin D3 (VitD3) could affect the natural course of chronic hepatitis C (CH-C) and the response to treatment with pegylated interferon (Peg-IFN) and ribavirin. Although several mechanisms for the favorable effects of VitD3 supplementation were reported, the total effect of VitD3 supplementation remains unclear. Previously, we reported that supplementation with 1(OH)VitD3 could enhance the Th1 response inducing not only a favorable immune response for viral eradication but also HCC control. Recently, the main treatment of CH-C should be direct acting antivirals (DAAs) without Peg-IFN. Peg-IFN is a strong immune-modulator. Therefore, an immunological analysis should be carried out to understand the effect of VitD3 after treatment of DAAs without Peg-IFN. The induction of a favorable immune response by adding VitD3 might be able to suppress the hepatocarcinogenesis after achieving SVR, especially in children and elderly patients with severe fibrosis lacking sufficient amounts of VitD3. PMID:28293078

  16. Antiviral treatment for chronic hepatitis B virus infection--immune modulation or viral suppression?

    NARCIS (Netherlands)

    E.H.C.J. Buster (Erik); H.L.A. Janssen (Harry)

    2006-01-01

    textabstractThe availability of nucleoside analogues has broadened treatment options for chronic hepatitis B virus (HBV ) infection. Registered treatment for chronic hepatitis B currently consists of (pegylated) interferon, lamivudine and adefovir, while entecavir is expected to be

  17. New direct-acting antivirals for patients with chronic HCV infection: can we monitor treatment using an HCV core antigen assay?

    Science.gov (United States)

    Alonso, R; Pérez-García, F; Ampuero, D; Reigadas, E; Bouza, E

    2017-03-01

    We evaluated the diagnostic usefulness of an HCV core antigen (HCV-Ag) assay in HCV-infected patients undergoing treatment with direct-acting antivirals. We analyzed 103 samples from 28 patients. Compared with RT-PCR, sensitivity was 96.2% and specificity was 100%. The correlation between techniques was excellent (Pearson coefficient: 0.871). HCV-Ag proved to be useful in patients with sustained viral response and in patients who experienced treatment failures.

  18. Behavior of antibiotics and antiviral drugs in sewage treatment plants and risk associated with their widespread use under pandemic condition

    OpenAIRE

    Ghosh, Gopal Chandra

    2009-01-01

    The concern for pharmaceutically active compounds (PhACs) as contaminants in the environment and the need to assess their environmental risk have greatly increased since the early nineties. Among PhACs, antibiotics and antiviral drugs are of important concern due to their role in growing antibiotic and antiviral drugs resistance among pathogenic bacteria and influenza viruses, respectively. Besides resistance issue, the compounds may upset sensitive ecosystems as they are designed to be highl...

  19. Antiviral Polymer Therapeutics

    DEFF Research Database (Denmark)

    Smith, Anton Allen Abbotsford

    2014-01-01

    The field of drug delivery is in essence an exercise in engineered pharmacokinetics. Methods of doing so have been developed through the introduction of a vehicle carrying the drug, either by encapsulation or covalent attachment. The emergence of polymer therapeutics in anticancer therapy has...... the examples of polymer therapeutics being applied as an antiviral treatment are few and far in-between. This work aims to explore antiviral therapeutics, specifically in context of hepatitis virus C (HCV) and HIV. The current treatment of hepatitis C consists of a combination of drugs, of which ribavirin....... Curiously, the therapeutic window of ribavirin was vastly improved in several of these polymers suggesting altered pharmacodynamics. The applicability of liver-targeting sugar moieties is likewise tested in a similarly methodical approach. The same technique of synthesis was applied with zidovudine to make...

  20. Novel Approaches for Targeting Antiviral Agents in the Treatment of Arena-, Bunya-, Flavi-, and Retroviral Infections

    Science.gov (United States)

    1989-05-22

    a variety of viral proteins including hepatitis B surface antigen, vesicular stomatitis virus glycoproteins, and adenovirus capsid proteins...infections. Moreover, this model could be used to establish a base from which therapeutic strategies to be employed in other more costly feline and primate...treatment of human AIDS. Most of the animal models (primate, bovine or feline ) considered relevant are too expensive for routine drug evaluation and too

  1. VIRAL- REACTIVATED PNEUMONIA DURING MECHANICAL VENTILATION: Is there need for antiviral treatment?

    Directory of Open Access Journals (Sweden)

    Alejandra eLópez-Giraldo

    2011-11-01

    Full Text Available Respiratory viruses are not a common cause of VAP. Herpesviridae (HSV and CMV are detected frequently in the lower respiratory tract of ventilated patients. HSV is detected between days 7 and 14 of IMV; presence of the virus does not necessarily imply pathogenicity, but the association with adverse clinical outcomes supports the hypothesis of a pathogenic role in a variable percentage of patients. Bronchopneumonitis associated with HSV should be considered in patients with prolonged IMV, reactivation with herpetic mucocutaneous lesions and those belonging to a risk population with burn injuries or acute lung injury.Reactivation of CMV is common in critically ill patients and usually occurs between days 14 and 21 in patients with defined risk factors. The potential pathogenic role of CMV seems clear in patients with acute lung injury and persistent respiratory failure in whom there is no isolation of bacterial agent as a cause of VAP. The best diagnostic test is not defined although lung biopsies should be considered in addition to the usual methods before starting specific treatment.The role of mimivirus is uncertain and is yet to be defined, but the serologic evidence of this new virus in the context of VAP appears to be associated with adverse clinical outcomes.

  2. YMDD motif mutations in chronic hepatitis B antiviral treatment naïve patients: a multi-center study

    Directory of Open Access Journals (Sweden)

    You-Wen Tan

    2012-06-01

    Full Text Available OBJECTIVE: This study aimed to determine the natural prevalence of variants of tyrosine-methionine-aspartic acid-aspartic acid (YMDD motif in patients with chronic hepatitis B (CHB, and to explore its relation with demographic and clinical features, hepatitis B virus (HBV genotypes, and HBV DNA levels. METHODS: A total of 1,042 antiviral treatment naïve CHB patients (including with lamivudine [LAM] in the past year were recruited from outpatient and inpatient departments of six centers from December 2008 to June 2010. YMDD variants were analyzed using the HBV drug resistance line probe assay (Inno-Lipa HBV-DR. HBV genotypes were detected with polymerase chain reaction (PCR microcosmic nucleic acid cross-ELISA, and HBV deoxyribonucleic acid (DNA was quantitated with real-time PCR. All serum samples underwent tests for HBV, HCV, and HDV with ELISA. RESULTS: YMDD variants were detected in 23.3% (243/1042 of CHB patients. YMDD mutation was accompanied by L180M mutation in 154 (76.9% patients. Both wild-type HBV and YMDD variant HBV were present in 231 of 243 patients. Interestingly, 12 patients had only YIDD and/or YVDD variants without wild YMDD motif. In addition, 27.2% (98/359 of HbeAg-positive patients had YMDD mutations, which was higher than that in HbeAg-negative patients (21.2%, 145/683. The incidence of YMDD varied among patients with different HBV genotypes, but the difference was not significant. Moreover, the incidence of YMDD in patients with high HBV DNA level was significantly higher than that in those with low HBV DNA level. CONCLUSION: Mutation of YMDD motif was detectable at a high rate in CHB patients in this study. The incidence of YMDD may be correlated with HBeAg and HBV DNA level.

  3. Subset-directed antiviral treatment of 142 herpesvirus patients with chronic fatigue syndrome

    Directory of Open Access Journals (Sweden)

    A Martin Lerner

    2010-05-01

    , and neurocognitive abnormalities improved or disappeared. Group B CFS patients (herpesvirus plus coinfections continued to have CFS.Keywords: valacyclovir, valganciclovir, treatment, chronic fatigue syndrome, CFS, Energy Index Point Score®, EIPS®

  4. Treatment with the smallpox antiviral tecovirimat (ST-246) alone or in combination with ACAM2000 vaccination is effective as a postsymptomatic therapy for monkeypox virus infection.

    Science.gov (United States)

    Berhanu, Aklile; Prigge, Jonathan T; Silvera, Peter M; Honeychurch, Kady M; Hruby, Dennis E; Grosenbach, Douglas W

    2015-07-01

    The therapeutic efficacies of smallpox vaccine ACAM2000 and antiviral tecovirimat given alone or in combination starting on day 3 postinfection were compared in a cynomolgus macaque model of lethal monkeypox virus infection. Postexposure administration of ACAM2000 alone did not provide any protection against severe monkeypox disease or mortality. In contrast, postexposure treatment with tecovirimat alone or in combination with ACAM2000 provided full protection. Additionally, tecovirimat treatment delayed until day 4, 5, or 6 postinfection was 83% (days 4 and 5) or 50% (day 6) effective.

  5. Bioprospecting of Red Sea Sponges for Novel Antiviral Pharmacophores

    KAUST Repository

    O'Rourke, Aubrie

    2015-05-01

    Natural products offer many possibilities for the treatment of disease. More than 70% of the Earth’s surface is ocean, and recent exploration and access has allowed for new additions to this catalog of natural treasures. The Central Red Sea off the coast of Saudi Arabia serves as a newly accessible location, which provides the opportunity to bioprospect marine sponges with the purpose of identifying novel antiviral scaffolds. Antivirals are underrepresented in present day clinical trials, as well as in the academic screens of marine natural product libraries. Here a high-throughput pipeline was initiated by prefacing the antiviral screen with an Image-based High-Content Screening (HCS) technique in order to identify candidates with antiviral potential. Prospective candidates were tested in a biochemical or cell-based assay for the ability to inhibit the NS3 protease of the West Nile Virus (WNV NS protease) as well as replication and reverse transcription of the Human Immunodeficiency Virus 1 (HIV-1). The analytical chemistry techniques of High-Performance Liquid Chromatograpy (HPLC), Liquid Chromatography-Mass Spectrometry (LC-MS), and Nuclear Magnetic Resonance (NMR) where used in order to identify the compounds responsible for the characteristic antiviral activity of the selected sponge fractions. We have identified a 3-alkyl pyridinium from Amphimedon chloros as the causative agent of the observed WNV NS3 protease inhibition in vitro. Additionally, we identified debromohymenialdisine, hymenialdisine, and oroidin from Stylissa carteri as prospective scaffolds capable of HIV-1 inhibition.

  6. The future of antiviral immunotoxins

    DEFF Research Database (Denmark)

    Spiess, K.; Høy Jakobsen, Mette; Kledal, Thomas N;

    2016-01-01

    There is a constant need for new therapeutic interventions in a wide range of infectious diseases. Over the past few years, the immunotoxins have entered the stage as promising antiviral treatments. Immunotoxins have been extensively explored in cancer treatment and have achieved FDA approval...

  7. High serum leptin is an independent risk factor for non-response patients with low viremia to antiviral treatment in chronic hepatitis C

    Institute of Scientific and Technical Information of China (English)

    Yuichiro Eguchi; Toshihiko Mizuta; Tsutomu Yasutake; Akitaka Hisatomi; Ryuichi Iwakiri; Iwata Ozaki; Kazuma Fujimoto

    2006-01-01

    AIM: To determine whether body weight and/or serum leptin were independent predictors of response to antiviral treatment in patients with chronic hepatitis C.METHODS: A retrospective evaluation was performed in 139 patients with chronic hepatitis C treated with interferon (IFN) from 1996 to 2000. Sustained response was defined as negative by hepatitis C virus (HCV) RNA analysis using PCR and normal transaminase at 24 wk after cessation of IFN therapy. Patients who remained positive for HCV RNA at the end of IFN treatment were defined as resistant to IFN therapy. Sex, age, body mass index (BMI) (≥ 25 vs < 25), complication of diabetes mellitus, serum leptin level (≥8.0 μg/L vs <8.0 μg/L),and the stage of liver fibrosis by needle biopsy (FL/F2 vs F3/F4) were examined.RESULTS: Sustained response was achieved in 33 patients (23.7%), while others failed to show a response to IFN therapy. Overall, the factors associated with sustained antiviral effects were HCV-RNA load, HCV genotype, serum leptin level, and stage of liver fibrosis evaluated by univariate analysis. BMI was not associated with any therapeutic effect of IFN. Multivariate analysis indicated that HCV-RNA load was a significant risk factor,but among the patients with low viremia (HCV-RNA < 100 MU/L), leptin level was an independent risk factor for IFN resistance. Namely, a high level of serum leptin attenuated the effect of IFN on both male and female patients with low viremia.CONCLUSION: High serum leptin level is a negative predictor of response to antiviral treatment in chronic hepatitis C with low viremia.

  8. Restrictions for reimbursement of direct-acting antiviral treatment for hepatitis C virus infection in Canada: a descriptive study

    Science.gov (United States)

    Marshall, Alison D.; Saeed, Sahar; Barrett, Lisa; Cooper, Curtis L.; Treloar, Carla; Bruneau, Julie; Feld, Jordan J.; Gallagher, Lesley; Klein, Marina B.; Krajden, Mel; Shoukry, Naglaa H.; Taylor, Lynn E.; Grebely, Jason

    2016-01-01

    Background: In Canada, interferon-free, direct-acting antiviral hepatitis C virus (HCV) regimens are costly. This presents challenges for universal drug coverage of the estimated 220 000 people with chronic HCV infection nationwide. The study objective was to appraise criteria for reimbursement of 4 HCV direct-acting antivirals in Canada. Methods: We reviewed the reimbursement criteria for simeprevir, sofosbuvir, ledipasvir-sofosbuvir and paritaprevir-ritonavir-ombitasvir plus dasabuvir in the 10 provinces and 3 territories. Data were extracted from April 2015 to June 2016. The primary outcomes extracted from health ministerial websites were: 1) minimum fibrosis stage required, 2) drug and alcohol use restrictions, 3) HIV coinfection restrictions and 4) prescriber type restrictions. Results: Overall, 85%-92% of provinces/territories limited access to patients with moderate fibrosis (Meta-Analysis of Histologic Data in Viral Hepatitis stage F2 or greater, or equivalent). There were no drug and alcohol use restrictions; however, several criteria (e.g., active injection drug use) were left to the discretion of the physician. Quebec did not reimburse simeprevir and sofosbuvir for people coinfected with HIV; no restrictions were found in the remaining jurisdictions. Prescriber type was restricted to specialists in up to 42% of provinces/territories. Interpretation: This review of criteria of reimbursement of HCV direct-acting antivirals in Canada showed substantial interjurisdictional heterogeneity. The findings could inform health policy and support the development and adoption of a national HCV strategy. PMID:28018873

  9. Hepatitis C Virus and Antiviral Drug Resistance

    Science.gov (United States)

    Kim, Seungtaek; Han, Kwang-Hyub; Ahn, Sang Hoon

    2016-01-01

    Since its discovery in 1989, hepatitis C virus (HCV) has been intensively investigated to understand its biology and develop effective antiviral therapies. The efforts of the previous 25 years have resulted in a better understanding of the virus, and this was facilitated by the development of in vitro cell culture systems for HCV replication. Antiviral treatments and sustained virological responses have also improved from the early interferon monotherapy to the current all-oral regimens using direct-acting antivirals. However, antiviral resistance has become a critical issue in the treatment of chronic hepatitis C, similar to other chronic viral infections, and retreatment options following treatment failure have become important questions. Despite the clinical challenges in the management of chronic hepatitis C, substantial progress has been made in understanding HCV, which may facilitate the investigation of other closely related flaviviruses and lead to the development of antiviral agents against these human pathogens. PMID:27784846

  10. Optimizing antiviral agents for hepatitis B management in malignant lymphomas

    Science.gov (United States)

    Ozoya, Oluwatobi O.; Chavez, Julio; Sokol, Lubomir

    2017-01-01

    The global scale of hepatitis B infection is well known but its impact is still being understood. Missed hepatitis B infection impacts lymphoma therapy especially increased risk of hepatitis B virus (HBV) reactivation and poor treatment outcomes. The presence of undiagnosed chronic hepatitis also undermines chronic HBV screening methods that are based on a positive HBsAg alone. The goal of this review is to evaluate the literature for optimizing antiviral therapy for lymphoma patients with HBV infection or at risk of HBV reactivation. Relevant articles for this review were identified by searching PubMed, Embase, Ovid Medline, and Scopus using the following terms, alone and in combination: “chronic hepatitis B”, “occult hepatitis B”, ”special groups”, “malignant lymphoma”, “non-Hodgkin’s lymphoma”, “Hodgkin’s lymphoma”, “immunocompromised host”, “immunosuppressive agents”, “antiviral”, “HBV reactivation”. The period of the search was restricted to a 15-year period to limit the search to optimizing antiviral agents for HBV infection in malignant lymphomas [2001–2016]. Several clinical practice guidelines recommend nucleos(t)ide analogues-entecavir, tenofovir and lamivudine among others. These agents are best initiated along with or prior to immunosuppressive therapy. Additional methods recommended for optimizing antiviral therapy include laboratory modalities such as HBV genotyping, timed measurements of HBsAg and HBV DNA levels to measure and predict antiviral treatment response. In conclusion, optimizing antiviral agents for these patients require consideration of geographic prevalence of HBV, cost of antiviral therapy or testing, screening modality, hepatitis experts, type of immunosuppressive therapy and planned duration of therapy.

  11. Influenza A(H1N1pdm09 virus suppresses RIG-I initiated innate antiviral responses in the human lung.

    Directory of Open Access Journals (Sweden)

    Wenxin Wu

    Full Text Available Influenza infection is a major cause of morbidity and mortality. Retinoic acid-inducible gene I (RIG-I is believed to play an important role in the recognition of, and response to, influenza virus and other RNA viruses. Our study focuses on the hypothesis that pandemic H1N1/09 influenza virus alters the influenza-induced proinflammatory response and suppresses host antiviral activity. We first compared the innate response to a clinical isolate of influenza A(H1N1pdm09 virus, OK/09, a clinical isolate of seasonal H3N2 virus, OK/06, and to a laboratory adapted seasonal H1N1 virus, PR8, using a unique human lung organ culture model. Exposure of human lung tissue to either pandemic or seasonal influenza virus resulted in infection and replication in alveolar epithelial cells. Pandemic virus induces a diminished RIG-I mRNA and antiviral cytokine response than seasonal virus in human lung. The suppression of antiviral response and RIG-I mRNA expression was confirmed at the protein level by ELISA and western blot. We performed a time course of RIG-I and interferon-β (IFN-β mRNA induction by the two viruses. RIG-I and IFN-β induction by OK/09 was of lower amplitude and shorter duration than that caused by PR8. In contrast, the pandemic virus OK/09 caused similar induction of proinflammatory cytokines, IL-8 and IL-6, at both the transcriptional and translational level as PR8 in human lung. Differential antiviral responses did not appear to be due to a difference in cellular infectivity as immunohistochemistry showed that both viruses infected alveolar macrophages and epithelial cells. These findings show that influenza A(H1N1pdm09 virus suppresses anti-viral immune responses in infected human lung through inhibition of viral-mediated induction of the pattern recognition receptor, RIG-I, though proinflammatory cytokine induction was unaltered. This immunosuppression of the host antiviral response by pandemic virus may have contributed to the more

  12. Surveillance of antiviral resistance markers in Argentina: detection of E119V neuraminidase mutation in a post-treatment immunocompromised patient

    Science.gov (United States)

    Pontoriero, Andrea; Avaro, Martín; Benedetti, Estefania; Russo, Mara; Czech, Andrea; Periolo, Natalia; Campos, Ana; Zamora, Ana; Baumeister, Elsa

    2016-01-01

    Although vaccines are the best means of protection against influenza, neuraminidase inhibitors are currently the main antiviral treatment available to control severe influenza cases. One of the most frequent substitutions in the neuraminidase (NA) protein of influenza A(H3N2) viruses during or soon after oseltamivir administration is E119V mutation. We describe the emergence of a mixed viral population with the E119E/V mutation in the NA protein sequence in a post-treatment influenza sample collected from an immunocompromised patient in Argentina. This substitution was identified by a real-time reverse transcriptase polymerase chain reaction (RT-PCR) protocol and was confirmed by direct Sanger sequencing of the original sample. In 2014, out of 1140 influenza samples received at the National Influenza Centre, 888 samples (78%) were A(H3N2) strains, 244 (21.3%) were type B strains, and 8 (0.7%) were A(H1N1)pdm09 strains. Out of 888 A(H3N2) samples, 842 were tested for the E119V substitution by quantitative RT-PCR: 841 A(H3N2) samples had the wild-type E119 genotype and in one sample, a mixture of viral E119/ V119 subpopulations was detected. Influenza virus surveillance and antiviral resistance studies can lead to better decisions in health policies and help in medical treatment planning, especially for severe cases and immunocompromised patients. PMID:27849220

  13. Dasatinib and Doxorubicin Treatment of Sarcoma Initiating Cells

    DEFF Research Database (Denmark)

    Aggerholm-Pedersen, Ninna; Demuth, Christina; Safwat, Akmal;

    2016-01-01

    Background. One of the major challenges affecting sarcoma treatment outcome, particularly that of metastatic disease, is resistance to chemotherapy. Cancer-initiating cells are considered a major contributor to this resistance. Methods. An immortalised nontransformed human stromal (mesenchymal) s...

  14. Emerging antiviral drugs.

    Science.gov (United States)

    De Clercq, Erik

    2008-09-01

    Foremost among the newly described antiviral agents that may be developed into drugs are, for the treatment of human papilloma virus (HPV) infections, cPrPMEDAP; for the treatment of herpes simplex virus (HSV) infections, BAY 57-1293; for the treatment of varicella-zoster virus (VZV) infections, FV-100 (prodrug of Cf 1743); for the treatment of cytomegalovirus (CMV) infections, maribavir; for the treatment of poxvirus infections, ST-246; for the treatment of hepatitis B virus (HBV) infections, tenofovir disoproxil fumarate (TDF) (which in the meantime has already been approved in the EU); for the treatment of various DNA virus infections, the hexadecyloxypropyl (HDP) and octadecyloxyethyl (ODE) prodrugs of cidofovir; for the treatment of orthomyxovirus infections (i.e., influenza), peramivir; for the treatment of hepacivirus infections (i.e., hepatitis C), the protease inhibitors telaprevir and boceprevir, the nucleoside RNA replicase inhibitors (NRRIs) PSI-6130 and R1479, and various non-nucleoside RNA replicase inhibitors (NNRRIs); for the treatment of human immunodeficiency virus (HIV) infections, integrase inhibitors (INIs) such as elvitegravir, nucleoside reverse transcriptase inhibitors (NRTIs) such as apricitabine, non-nucleoside reverse transcriptase inhibitors (NNRTIs) such as rilpivirine and dapivirine; and for the treatment of both HCV and HIV infections, cyclosporin A derivatives such as the non-immunosuppressive Debio-025.

  15. Antiviral Treatment of HCV-Infected Patients with B-Cell Non-Hodgkin Lymphoma: ANRS HC-13 Lympho-C Study

    Science.gov (United States)

    Alric, Laurent; Besson, Caroline; Lapidus, Nathanael; Jeannel, Juliette; Michot, Jean-Marie; Cacoub, Patrice; Canioni, Danielle; Pol, Stanislas; Davi, Frédéric; Rabiega, Pascaline; Ysebaert, Loic; Bonnet, Delphine; Hermine, Olivier

    2016-01-01

    Hepatitis C virus (HCV) infection is associated with lymphoproliferative disorders and B-cell non-Hodgkin lymphomas (B-NHLs). Evaluation of the efficacy and safety profiles of different antiviral therapies in HCV patients with B-NHL is warranted. Methods: First, we evaluated the sustained virologic response (SVR) and safety of Peg-interferon-alpha (Peg-IFN) + ribavirin +/- first protease inhibitors (PI1s) therapy in 61 HCV patients with B-NHL enrolled in a nationwide observational survey compared with 94 matched HCV-infected controls without B-NHL. In a second series, interferon-free regimens using a newly optimal combination therapy with direct-acting antiviral drugs (DAAs) were evaluated in 10 patients with HCV and B-NHL. Results: The main lymphoma type was diffuse large B-cell lymphoma (38%) followed by marginal zone lymphoma (31%). In the multivariate analysis, patients with B-NHL treated by Peg-IFN-based therapy exhibited a greater SVR rate compared with controls, 50.8% vs 30.8%, respectively, p<0.01, odds ratio (OR) = 11.2 [2.3, 52.8]. B-NHL response was better (p = 0.02) in patients with SVR (69%) than in patients without SVR (31%). Premature discontinuation of Peg-IFN-based therapy was significantly more frequent in the B-NHL group (19.6%) compared with the control group (6.3%), p<0.02. Overall, survival was significantly enhanced in the controls than in the B-NHL group (hazard ratio = 34.4 [3.9, 304.2], p< 0.01). Using DAAs, SVR was achieved in 9/10 patients (90%). DAAs were both well tolerated and markedly efficient. Conclusions: The virologic response of HCV-associated B-NHL is high. Our study provides a comprehensive evaluation of different strategies for the antiviral treatment of B-NHL associated with HCV infection. PMID:27749916

  16. Gastrointestinal events and association with initiation of treatment for osteoporosis

    Directory of Open Access Journals (Sweden)

    Modi A

    2015-11-01

    Full Text Available Ankita Modi,1 Ethel S Siris,2 Jackson Tang,3 Shiva Sajjan,1 Shuvayu S Sen1 1Center for Observational and Real-World Evidence, Merck & Co., Inc, Kenilworth, NJ, 2Toni Stabile Osteoporosis Center, Columbia University Medical Center, NY Presbyterian Hospital, New York, NY, 3Asclepius Analytics Ltd, Brooklyn, NY, USA Background: Preexisting gastrointestinal (GI events may deter the use of pharmacologic treatment in patients diagnosed with osteoporosis (OP. The objective of this study was to examine the association between preexisting GI events and OP pharmacotherapy initiation among women diagnosed with OP. Methods: The study utilized claims data from a large US managed care database to identify women aged ≥55 years with a diagnosis code for OP (index date during 2002–2009. Patients with a claim for pharmacologic OP treatment in the 12-month pre-index period (baseline were excluded. OP treatment initiation in the post-index period was defined as a claim for bisphosphonates (alendronate, ibandronate, risedronate, zoledronic acid, calcitonin, raloxifene, or teriparatide. During the post-index period (up to 12 months, GI events were identified before treatment initiation. A time-dependent Cox regression model was used to investigate the likelihood of initiating any OP treatment. Among patients initiating OP treatment, a discrete choice model was utilized to assess the relationship between post-index GI events and likelihood of initiating with a bisphosphonate versus a non-bisphosphonate. Results: In total, 65,344 patients (mean age 66 years were included; 23.7% had a GI event post diagnosis and before treatment initiation. Post-index GI events were associated with a 75% lower likelihood of any treatment initiation (hazard ratio 0.25; 95% confidence interval 0.24–0.26. Among treated patients (n=23,311, those with post-index GI events were 39% less likely to receive a bisphosphonate versus a non-bisphosphonate (odds ratio 0.61; 95% confidence

  17. [Treatment's initiation in chronic inflammatory demyelinating polyradiculopathy (CIDP)].

    Science.gov (United States)

    Uzenot, D; Azulay, J-P; Pouget, J

    2007-09-01

    Treatment's initiation in chronic inflammatory demyelinating polyradiculopathy (CIDP) remains a difficult medical decision. Only plasma exchanges, intravenous immunoglobulins (IVIg) and corticosteroids are proven effective treatments. Immunosuppressors are actually not first-line treatments in CIDP. Particular CIDP forms are associated with different response to treatments: pure motor CIDP should be treated by IVIg, and corticosteroids should only carefully be used in Lewis-Sumner syndrome. Otherwise, IVIg are first-line treatment in diabetic patients. Patients must be informed of side's effects and expected clinical effects. Early treatment was actually not proved to prevent axonal damages in CIDP patients, and waiting seems to be the best therapeutic option in poorly symptomatic patients. Recently, clinical guidelines were proposed to help clinician in this treatment choice, but there is no consensus about the best dose, duration or administration way to CIDP treatments. Further studies should be performed to clarify these points and to determine immunosuppressor agents place in treatment strategy.

  18. USE OF HEMATOPOIETIC GROWTH FACTOR IN THE MANAGEMENT OF HEMATOLOGICAL SIDE EFFECTS ASSOCIATED TO ANTIVIRAL TREATMENT FOR HCV HEPATITIS

    Directory of Open Access Journals (Sweden)

    Paola Mancino

    2010-03-01

    Full Text Available Haematological abnormalities are common during combination antiviral therapy for chronic hepatitis C. Although dose reduction or discontinuation can easily treat these side effects, they can adversely affect the efficacy of combination antiviral therapy reducing the likelihood of a sustained viral response (SVR. To avoid potentially diminishing a patient’s chance of response, many physicians have begun using growth factors off-label to manage anaemia and neutropenia in hepatitis C. Haematopoietic growth factors are generally well tolerated and they may be useful for managing haematological side effects of anti-HCV therapy improving patients’ quality of life. To date, the role and benefit of these agents during anti-HCV therapy and their positive impact on SVR have not conclusively determined in the published studies. However, the possibility of a benefit to individual outpatients remains, and an individualized approach is recommended. This review explores the incidence, clinical significance, and management of anaemia, neutropenia and thrombocytopenia associated with combination therapy for HCV infection.

  19. [Analysis of the causes leading to withdrawal of the treatment with triple antiviral therapy for hepatitis C patients].

    Science.gov (United States)

    Ruiz Ramos, J; Lorente Fernández, L; Gil Gómez, I; Cueto Sola, M; Monte Boquet, E; Poveda Andrés, J L

    2014-05-01

    Objetivo: Evaluar las causas de suspensión de tratamientofrente a Hepatitis C que reciben triple terapia antiviral (peginterferon+ ribavirina + inhibidor de proteasa).Métodos: Estudio observacional retrospectivo de pacientes queiniciaron triple terapia antiviral entre enero 2012 - marzo 2013y suspendieron el tratamiento antes de completar el mismo.Resultados: De 156 pacientes que iniciaron triple terapia, 41interrumpieron el tratamiento: Diecinueve por toxicidad, siendodermatológica en siete pacientes (36,8%), intolerancia en seis(31,6%) y hematológica en cuatro (15,8%). Dieciséis pacientessuspendieron todo el tratamiento por ineficacia. El grupo depacientes con mayor porcentaje de fracasos por ineficacia fueronlos “no respondedores” (32,3%) mientras que el grupo depacientes “recidivantes” fueron el grupo con mayor porcentajede suspensiones por toxicidad (15,6%). Dos pacientes fallecierondurante el tratamiento por neumonía.Conclusiones: La triple terapia frente a VHC está asociada a unnúmero importante de fracasos terapéuticos tanto por toxicidadcomo por ineficacia.

  20. Efficacy of Alendronate and Cholecalciferol Combination in the Treatment of Osteoporosis in Patients with Chronic Viral Hepatitis Receiving Antiviral Therapy: Report of Two Cases

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    İlke Coşkun Benlidayı

    2015-08-01

    Full Text Available In this case report, the efficacy of 12-month alendronate and cholecalciferol combination therapy for the treatment of osteoporosis in two male patients with chronic viral hepatitis aged above 60 years who were on antiviral treatment was evaluated. The patients were diagnosed with osteoporosis via dual energy x-ray absorptiometry while receiving 245 mg tenofovir disoproxil fumarate once daily and started on alendronate and cholecalciferol combination (70 mg/2800 IU. Baseline T-scores of the two patients were -2.6 and -4.9, respectively. Baseline bone mineral density (BMD and 25(OHD (ng/ml values were compared with post-treatment values. Regarding the first case, following treatment, lumbar, femoral neck and total hip BMD values were improved by 1.9%, 5.2% and 13.8%, respectively. In the second case, L1-L4 lumbar, femoral neck and total hip BMD values were improved by 23.2%, 25.9% and 14.8%, respectively. However, when pre- and posttreatment 25(OHD levels were compared, a decrease was observed in both patients. In conclusion, 12-month treatment with alendronate and cholecalciferol combination improved BMD values, in patients with chronic viral hepatitis who were on antiviral therapy. Considering that tenofovir therapy effects vitamin D metabolism independently in these patients, it is necessary to control 25(OHD levels in a regular basis and to support the patient with adequate vitamin D supplementation, in order to optimize serum vitamin D levels and prevent from vitamin D insufficiency. (Turkish Journal of Osteoporosis 2015;21: 96-9

  1. Use of Direct-Acting Antivirals for the Treatment of Hepatitis C Virus-Associated Oral Lichen Planus: A Case Report

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    Kenji Misaka

    2016-10-01

    Full Text Available Hepatitis C virus (HCV is frequently associated with various extrahepatic manifestations such as autoimmune features and immune complex deposit diseases. Oral lichen planus (OLP is one of the representative extrahepatic manifestations of HCV infection. Direct-acting antivirals (DAA are highly effective and safe for the eradication of HCV. However, there is a lack of information regarding the association between HCV-associated OLP and interferon (IFN-free DAA therapy. Herein, we present the case of a 60-year-old female who was diagnosed with OLP during routine periodontal treatment by a dentist. The patient was referred for hepatitis C treatment using IFN-free DAA, which resulted in the improvement of the symptoms of OLP. This case represents the safety and efficacy of IFN-free DAAs in patients with HCV-associated OLP. However, long-term follow-up studies are required to elucidate the therapeutic effects of this therapy in these patients.

  2. Use of Direct-Acting Antivirals for the Treatment of Hepatitis C Virus-Associated Oral Lichen Planus: A Case Report

    Science.gov (United States)

    Misaka, Kenji; Kishimoto, Takashi; Kawahigashi, Yuji; Sata, Michio; Nagao, Yumiko

    2016-01-01

    Hepatitis C virus (HCV) is frequently associated with various extrahepatic manifestations such as autoimmune features and immune complex deposit diseases. Oral lichen planus (OLP) is one of the representative extrahepatic manifestations of HCV infection. Direct-acting antivirals (DAA) are highly effective and safe for the eradication of HCV. However, there is a lack of information regarding the association between HCV-associated OLP and interferon (IFN)-free DAA therapy. Herein, we present the case of a 60-year-old female who was diagnosed with OLP during routine periodontal treatment by a dentist. The patient was referred for hepatitis C treatment using IFN-free DAA, which resulted in the improvement of the symptoms of OLP. This case represents the safety and efficacy of IFN-free DAAs in patients with HCV-associated OLP. However, long-term follow-up studies are required to elucidate the therapeutic effects of this therapy in these patients. PMID:27920651

  3. 乙型肝炎肝硬化抗病毒治疗研究进展%Progress in the antiviral treatment of HBV-related cirrhosis

    Institute of Scientific and Technical Information of China (English)

    黄英男; 吴昊

    2013-01-01

    Chronic hepatitis B virus (HBV) infection is one of the major global public health problems. Every year,about 3% of the chronic hepatitis B patients develop cirrhosis. Without efficient anti-viral treatment, these patients may develop decompensated cirrhosis or hepatocellular carcinoma (HCC). Antiviral treatment, including interferon (IFN) and nucleos (t) ide analogues (NUCs) is important in the cirrhotic patients. IFN can suppress HBV replication and mediate the immunologic function with considerable side effects. It can only be used in well-compensated cirrhosis. NUCs include lamivudine (LAM) , adefovir dipivoxil ( ADV) , enteccavir (ETV) , telbivudine (TEB) and tenofovir disoproxil fumarate ( TDF). They can suppress HBV replication and reduce the long-term complications. They have fewer side effects, but are easy to develop drug resisitance. This review focused on the recent progress in the antiviral treatment of HBV-related cirrhosis.%慢性乙肝病毒感染是全世界主要的公共卫生问题之一,每年有约3%的慢性乙型肝炎患者发展为肝硬化.若无有效的抗病毒治疗手段,这些乙肝患者会发展为失代偿期肝硬化或肝细胞癌.对于肝硬化患者,干扰素(interferon,IFN)和核苷类似物[nucleos(t)ide analogues,NUCs]是重要的抗病毒药物.IFN能抑制乙肝病毒复制并调节免疫功能,但不良反应较大,仅可用于情况较好的代偿期肝硬化患者;NUCs包括拉米夫定、阿德福韦酯、恩替卡韦、替比夫定及替诺福韦酯,能够抑制病毒复制,减少肝硬化患者远期并发症的发生,不良反应小但容易发生病毒耐药.本文对乙肝肝硬化的抗病毒治疗新进展作一综述.

  4. Antiviral, antifungal, and antiparasitic activities of fluoroquinolones optimized for treatment of bacterial infections: a puzzling paradox or a logical consequence of their mode of action?

    Science.gov (United States)

    Dalhoff, A

    2015-04-01

    This review summarizes evidence that commercially available fluoroquinolones used for the treatment of bacterial infections are active against other non-bacterial infectious agents as well. Any of these fluoroquinolones exerts, in parallel to its antibacterial action, antiviral, antifungal, and antiparasitic actions at clinically achievable concentrations. This broad range of anti-infective activities is due to one common mode of action, i.e., the inhibition of type II topoisomerases or inhibition of viral helicases, thus maintaining the selective toxicity of fluoroquinolones inhibiting microbial topoisomerases at low concentrations but mammalian topoisomerases at much higher concentrations. Evidence suggests that standard doses of the fluoroquinolones studied are clinically effective against viral and parasitic infections, whereas higher doses administered topically were active against Candida spp. causing ophthalmological infections. Well-designed clinical studies should be performed to substantiate these findings.

  5. The Risk of Hepatocellular Carcinoma After Directly Acting Antivirals for Hepatitis C Virus Treatment in Liver Transplanted Patients: Is It Real?

    Science.gov (United States)

    Strazzulla, Alessio; Maria Rita Iemmolo, Rosa; Carbone, Ennio; Concetta Postorino, Maria; Mazzitelli, Maria; De Santis, Mario; Di Benedetto, Fabrizio; Maria Cristiani, Costanza; Costa, Chiara; Pisani, Vincenzo; Torti, Carlo

    2016-01-01

    Introduction Since directly acting antivirals (DAAs) for treatment of hepatitis C virus (HCV) were introduced, conflicting data emerged about the risk of hepatocellular carcinoma (HCC) after interferon (IFN)-free treatments. We present a case of recurrent, extra-hepatic HCC in a liver-transplanted patient soon after successful treatment with DAAs, along with a short review of literature. Case Presentation In 2010, a 53-year old man, affected by chronic HCV (genotype 1) infection and decompensated cirrhosis, underwent liver resection for HCC and subsequently received orthotopic liver transplantation. Then, HCV relapsed and, in 2013, he was treated with pegylated-IFN plus ribavirin; but response was null. In 2014, he was treated with daclatasvir plus simeprevir to reach sustained virological response. At baseline and at the end of HCV treatment, computed tomography (CT) scan of abdomen excluded any lesions suspected for HCC. However, alpha-fetoprotein was 2.9 ng/mL before DAAs, increasing up to 183.1 ng/mL at week-24 of follow-up after the completion of therapy. Therefore, CT scan of abdomen was performed again, showing two splenic HCC lesions. Conclusions Overall, nine studies have been published about the risk of HCC after DAAs. Patients with previous HCC should be carefully investigated to confirm complete HCC remission before starting, and proactive follow-up should be performed after DAA treatment. PMID:28070200

  6. HOMA, BMI, and Serum Leptin Levels Variations during Antiviral Treatment Suggest Virus-Related Insulin Resistance in Noncirrhotic, Nonobese, and Nondiabetic Chronic Hepatitis C Genotype 1 Patients

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    Alessandro Grasso

    2015-01-01

    Full Text Available Objective. To investigate the relationship between insulin resistance and viral load decay in nondiabetic and noncirrhotic genotype 1 chronic HCV patients during peginterferon and ribavirin treatment and the possible influence of BMI and leptin as metabolic confounders. Methods. 75 consecutive noncirrhotic, nonobese, and nondiabetic patients with genotype 1 chronic hepatitis C treated with peginterferon alpha 2a plus ribavirin were evaluated. HOMA-IR, serum leptin, and BMI were measured in all patients at baseline and at weeks 12 and 48, whereas viral load was measured at the same time points and then 24 weeks after the end of treatment. Results. HOMA-IR was significantly associated with both BMI and leptin at baseline. During peginterferon plus ribavirin treatment, there was a significant reduction of HOMA-IR at weeks 12 and 48 from baseline (P=0.033 and 0.048, resp. in patients who achieved an early viral load decay (EVR, a trend not observed in patients who not achieved EVR. No variations during treatment were observed regarding BMI and leptin irrespective of EVR. Conclusion. The early reduction of HOMA-IR but not of BMI and leptin during antiviral treatment in noncirrhotic, chronic hepatitis C genotype 1 patients who achieved EVR suggests a viral genesis of insulin resistance in patients with nonmetabolic phenotype.

  7. Initial application of digital tomosynthesis to improve brachytherapy treatment planning

    Science.gov (United States)

    Baydush, Alan H.; Mirzaei McKee, Mahta; King, June; Godfrey, Devon J.

    2007-03-01

    We present preliminary investigations that examine the feasibility of incorporating volumetric images generated using digital tomosynthesis into brachytherapy treatment planning. The Integrated Brachytherapy Unit (IBU) at our facility consists of an L-arm, C-arm isocentric motion system with an x-ray tube and fluoroscopic imager attached. Clinically, this unit is used to generate oblique, anterior-posterior, and lateral images for simple treatment planning and dose prescriptions. Oncologists would strongly prefer to have volumetric data to better determine three dimensional dose distributions (dose-volume histograms) to the target area and organs at risk. Moving the patient back and forth to CT causes undo stress on the patient, allows extensive motion of organs and treatment applicators, and adds additional time to patient treatment. We propose to use the IBU imaging system with digital tomosynthesis to generate volumetric patient data, which can be used for improving treatment planning and overall reducing treatment time. Initial image data sets will be acquired over a limited arc of a human-like phantom composed of real bones and tissue equivalent material. A brachytherapy applicator will be incorporated into one of the phantoms for visualization purposes. Digital tomosynthesis will be used to generate a volumetric image of this phantom setup. This volumetric image set will be visually inspected to determine the feasibility of future incorporation of these types of images into brachytherapy treatment planning. We conclude that initial images using the tomosynthesis reconstruction technique show much promise and bode well for future work.

  8. Benzodiazepines and adequacy of initial antidepressant treatment for depression.

    Science.gov (United States)

    Pfeiffer, Paul N; Ganoczy, Dara; Zivin, Kara; Valenstein, Marcia

    2011-06-01

    In short-term efficacy studies, coprescription of a benzodiazepine improves first-month adherence and response to antidepressant treatment. We used Veterans Health Administration data to examine the impact of coprescribed benzodiazepines on initial antidepressant adherence in routine clinical practice and the risks of long-term benzodiazepine use, abuse, and dependence. Our study population was 43,915 Veterans Health Administration patients diagnosed with depression and started on an antidepressant between October 2006 and September 2007. Using logistic regression, adjusting for demographic and clinical covariates, we predicted the likelihood that patients received antidepressant treatment for an adequate duration (90 days), with our primary independent variable of interest being receipt of a benzodiazepine on the same day as the start of the antidepressant. We also assessed the frequency and characteristics of patients whose benzodiazepine use persisted for 1 year or who were diagnosed with anxiolytic abuse or dependence after receiving combined treatment. The adjusted probability of receiving antidepressant treatment of adequate duration was 42.4% for patients who received a benzodiazepine with their initial antidepressant compared with 39.3% for patients initially treated with an antidepressant alone (P benzodiazepines for at least 1 year, and 0.7% were diagnosed with anxiolytic abuse or dependence. Anxiolytic abuse or dependence, but not long-term benzodiazepine use, was associated with other substance use disorders. These findings should be considered by clinicians when assessing the individual risks and benefits of combining a benzodiazepine with antidepressant treatment.

  9. Ethical issues in the initiation and termination of treatment.

    Science.gov (United States)

    Kilner, J F

    1990-03-01

    This report addresses the ethical issues involved in decisions to initiate and terminate treatment. A general framework is constructed and then two illustrative cases are discussed. The framework is developed in three stages. First, the issue of guiding ethical principles is examined, with a multiple-principle approach being adopted. Second, common models of the care-giver/patient relationship (warrior, parental, contractual, covenantal) are identified, and their varying impacts on treatment decisions are explained and assessed. Third, specific criteria for determining when to initiate and terminate treatment are introduced. Two criteria (willingness and medical benefit) are commended in the context of initiating treatment, while three distinctions (willing v unwilling, passive v active, and terminal v nonterminal) are found to be particularly helpful when deciding if treatment should be terminated. Two illustrative cases involve end-stage renal disease (ESRD). The first describes a noncompliant and abusive intravenous (IV) drug user on hemodialysis who wants to continue on dialysis and eventually receive a living-related donor kidney transplant. The second describes a patient's decisions to refuse feeding gastrostomy and jejunostomy, any further surgical or diagnostic intervention, and eventually dialysis-though only after a period of time when he wants dialysis alone to continue.

  10. Registering initial defaulters and reporting on their treatment outcomes.

    Science.gov (United States)

    Harries, A D; Rusen, I D; Chiang, C-Y; Hinderaker, S G; Enarson, D A

    2009-07-01

    This Unresolved Issues article highlights three original articles that appeared last year in the Journal discussing the phenomenon of initial defaulters. There are three important challenges with patients that appear in the laboratory sputum register but are not recorded in the tuberculosis (TB) patient register: the first is how to identify these patients, trace them and get them on to treatment as soon as possible; the second is how to register and report on these cases as part of the case-finding component of TB control; and the third is whether to include these initial default patients in the cohort analysis of treatment outcomes. We recommend a step-wise approach to these challenges and advocate that these patients be included, wherever possible, in the TB patient register and in the cohort analysis of treatment outcomes.

  11. Successful Treatment of Corticosteroid with Antiviral Therapy for a Neonatal Liver Failure with Disseminated Herpes Simplex Virus Infection.

    Science.gov (United States)

    Maeba, Shinji; Hasegawa, Shunji; Shimomura, Maiko; Ichimura, Takuya; Takahashi, Kazumasa; Motoyama, Masashi; Fukunaga, Shinnosuke; Ito, Yoshinori; Ichiyama, Takashi; Ohga, Shouichi

    2015-10-01

    Background Herpes simplex virus (HSV) infection carries one of the poorest outcomes of neonatal liver failure (NLF). Neonates with disseminated HSV infection can develop hemophagocytic lymphohistiocytosis (HLH), and occasionally need orthotopic liver transplantation. Early interventions may be critical for the cure of NLF. Case Report We describe herewith a 6-day-old neonate with fulminant hepatic failure due to disseminated HSV-1 infection, who successfully responded to high-dose corticosteroid therapy 72 hours after the onset of disease. Preceding acyclovir, gamma globulin, and exchange blood transfusion therapies failed to control the disease. Methylprednisolone pulse therapy led to a drastic improvement of liver function and cytokine storms, and prevented the disease progression to HLH. Sustained levels of plasma and cerebrospinal fluid HSV DNA declined after prolonged acyclovir therapy. Bilateral lesions of the periventricular white matter areas, assessed by magnetic resonance imaging, disappeared at 3 months of age. The infant showed normal growth and development at 4 years of age. Conclusion Early anti-hypercytokinemia therapy using corticosteroid, and prolonged antiviral therapy might only provide the transplantation-free cure of NLF with HSV dissemination.

  12. Successful Treatment of Corticosteroid with Antiviral Therapy for a Neonatal Liver Failure with Disseminated Herpes Simplex Virus Infection

    Directory of Open Access Journals (Sweden)

    Shinji Maeba

    2015-10-01

    Full Text Available Background - Herpes simplex virus (HSV infection carries one of the poorest outcomes of neonatal liver failure (NLF. Neonates with disseminated HSV infection can develop hemophagocytic lymphohistiocytosis (HLH, and occasionally need orthotopic liver transplantation. Early interventions may be critical for the cure of NLF. Case Report - We describe herewith a 6-day-old neonate with fulminant hepatic failure due to disseminated HSV-1 infection, who successfully responded to high-dose corticosteroid therapy 72 hours after the onset of disease. Preceding acyclovir, gamma globulin, and exchange blood transfusion therapies failed to control the disease. Methylprednisolone pulse therapy led to a drastic improvement of liver function and cytokine storms, and prevented the disease progression to HLH. Sustained levels of plasma and cerebrospinal fluid HSV DNA declined after prolonged acyclovir therapy. Bilateral lesions of the periventricular white matter areas, assessed by magnetic resonance imaging, disappeared at 3 months of age. The infant showed normal growth and development at 4 years of age. Conclusion - Early anti-hypercytokinemia therapy using corticosteroid, and prolonged antiviral therapy might only provide the transplantation-free cure of NLF with HSV dissemination.

  13. Antiviral oseltamivir is not removed or degraded in normal sewage water treatment: implications for development of resistance by influenza A virus.

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    Jerker Fick

    Full Text Available Oseltamivir is the main antiviral for treatment and prevention of pandemic influenza. The increase in oseltamivir resistance reported recently has therefore sparked a debate on how to use oseltamivir in non pandemic influenza and the risks associated with wide spread use during a pandemic. Several questions have been asked about the fate of oseltamivir in the sewage treatment plants and in the environment. We have assessed the fate of oseltamivir and discuss the implications of environmental residues of oseltamivir regarding the occurrence of resistance. A series of batch experiments that simulated normal sewage treatment with oseltamivir present was conducted and the UV-spectra of oseltamivir were recorded.Our experiments show that the active moiety of oseltamivir is not removed in normal sewage water treatments and is not degraded substantially by UV light radiation, and that the active substance is released in waste water leaving the plant. Our conclusion is that a ubiquitous use of oseltamivir may result in selection pressures in the environment that favor development of drug-resistance.

  14. Clinical Implications of Antiviral Resistance in Influenza

    OpenAIRE

    Li, Timothy C. M.; Chan, Martin C. W.; Nelson Lee

    2015-01-01

    Influenza is a major cause of severe respiratory infections leading to excessive hospitalizations and deaths globally; annual epidemics, pandemics, and sporadic/endemic avian virus infections occur as a result of rapid, continuous evolution of influenza viruses. Emergence of antiviral resistance is of great clinical and public health concern. Currently available antiviral treatments include four neuraminidase inhibitors (oseltamivir, zanamivir, peramivir, laninamivir), M2-inibitors (amantadin...

  15. Self-interest versus group-interest in antiviral control.

    Directory of Open Access Journals (Sweden)

    Michiel van Boven

    Full Text Available Antiviral agents have been hailed to hold considerable promise for the treatment and prevention of emerging viral diseases like H5N1 avian influenza and SARS. However, antiviral drugs are not completely harmless, and the conditions under which individuals are willing to participate in a large-scale antiviral drug treatment program are as yet unknown. We provide population dynamical and game theoretical analyses of large-scale prophylactic antiviral treatment programs. Throughout we compare the antiviral control strategy that is optimal from the public health perspective with the control strategy that would evolve if individuals make their own, rational decisions. To this end we investigate the conditions under which a large-scale antiviral control program can prevent an epidemic, and we analyze at what point in an unfolding epidemic the risk of infection starts to outweigh the cost of antiviral treatment. This enables investigation of how the optimal control strategy is moulded by the efficacy of antiviral drugs, the risk of mortality by antiviral prophylaxis, and the transmissibility of the pathogen. Our analyses show that there can be a strong incentive for an individual to take less antiviral drugs than is optimal from the public health perspective. In particular, when public health asks for early and aggressive control to prevent or curb an emerging pathogen, for the individual antiviral drug treatment is attractive only when the risk of infection has become non-negligible. It is even possible that from a public health perspective a situation in which everybody takes antiviral drugs is optimal, while the process of individual choice leads to a situation where nobody is willing to take antiviral drugs.

  16. Genetic Diversity and Selective Pressure in Hepatitis C Virus Genotypes 1–6: Significance for Direct-Acting Antiviral Treatment and Drug Resistance

    Directory of Open Access Journals (Sweden)

    Lize Cuypers

    2015-09-01

    Full Text Available Treatment with pan-genotypic direct-acting antivirals, targeting different viral proteins, is the best option for clearing hepatitis C virus (HCV infection in chronically infected patients. However, the diversity of the HCV genome is a major obstacle for the development of antiviral drugs, vaccines, and genotyping assays. In this large-scale analysis, genome-wide diversity and selective pressure was mapped, focusing on positions important for treatment, drug resistance, and resistance testing. A dataset of 1415 full-genome sequences, including genotypes 1–6 from the Los Alamos database, was analyzed. In 44% of all full-genome positions, the consensus amino acid was different for at least one genotype. Focusing on positions sharing the same consensus amino acid in all genotypes revealed that only 15% was defined as pan-genotypic highly conserved (≥99% amino acid identity and an additional 24% as pan-genotypic conserved (≥95%. Despite its large genetic diversity, across all genotypes, codon positions were rarely identified to be positively selected (0.23%–0.46% and predominantly found to be under negative selective pressure, suggesting mainly neutral evolution. For NS3, NS5A, and NS5B, respectively, 40% (6/15, 33% (3/9, and 14% (2/14 of the resistance-related positions harbored as consensus the amino acid variant related to resistance, potentially impeding treatment. For example, the NS3 variant 80K, conferring resistance to simeprevir used for treatment of HCV1 infected patients, was present in 39.3% of the HCV1a strains and 0.25% of HCV1b strains. Both NS5A variants 28M and 30S, known to be associated with resistance to the pan-genotypic drug daclatasvir, were found in a significant proportion of HCV4 strains (10.7%. NS5B variant 556G, known to confer resistance to non-nucleoside inhibitor dasabuvir, was observed in 8.4% of the HCV1b strains. Given the large HCV genetic diversity, sequencing efforts for resistance testing purposes may

  17. Genetic Diversity and Selective Pressure in Hepatitis C Virus Genotypes 1–6: Significance for Direct-Acting Antiviral Treatment and Drug Resistance

    Science.gov (United States)

    Cuypers, Lize; Li, Guangdi; Libin, Pieter; Piampongsant, Supinya; Vandamme, Anne-Mieke; Theys, Kristof

    2015-01-01

    Treatment with pan-genotypic direct-acting antivirals, targeting different viral proteins, is the best option for clearing hepatitis C virus (HCV) infection in chronically infected patients. However, the diversity of the HCV genome is a major obstacle for the development of antiviral drugs, vaccines, and genotyping assays. In this large-scale analysis, genome-wide diversity and selective pressure was mapped, focusing on positions important for treatment, drug resistance, and resistance testing. A dataset of 1415 full-genome sequences, including genotypes 1–6 from the Los Alamos database, was analyzed. In 44% of all full-genome positions, the consensus amino acid was different for at least one genotype. Focusing on positions sharing the same consensus amino acid in all genotypes revealed that only 15% was defined as pan-genotypic highly conserved (≥99% amino acid identity) and an additional 24% as pan-genotypic conserved (≥95%). Despite its large genetic diversity, across all genotypes, codon positions were rarely identified to be positively selected (0.23%–0.46%) and predominantly found to be under negative selective pressure, suggesting mainly neutral evolution. For NS3, NS5A, and NS5B, respectively, 40% (6/15), 33% (3/9), and 14% (2/14) of the resistance-related positions harbored as consensus the amino acid variant related to resistance, potentially impeding treatment. For example, the NS3 variant 80K, conferring resistance to simeprevir used for treatment of HCV1 infected patients, was present in 39.3% of the HCV1a strains and 0.25% of HCV1b strains. Both NS5A variants 28M and 30S, known to be associated with resistance to the pan-genotypic drug daclatasvir, were found in a significant proportion of HCV4 strains (10.7%). NS5B variant 556G, known to confer resistance to non-nucleoside inhibitor dasabuvir, was observed in 8.4% of the HCV1b strains. Given the large HCV genetic diversity, sequencing efforts for resistance testing purposes may need to be

  18. Ribavirin at the Era of Novel Direct Antiviral Agents for the Treatment of Hepatitis C Virus Infection: Relevance of Pharmacological Monitoring

    Directory of Open Access Journals (Sweden)

    Pierre Pradat

    2014-01-01

    Full Text Available Ribavirin is often used for the treatment of hepatitis C virus (HCV infection. Although its mechanisms of action remain to be clearly elucidated, ribavirin plays a beneficial role for achieving virological response and decreasing the rate of virological relapse after treatment cessation. However, ribavirin may induce side effects leading to early treatment discontinuation. Among them, hemolytic anemia is the most frequent and results from intraerythrocyte accumulation. Pharmacological studies have shown that early ribavirin exposure assessed by the area under the curve (AUC at day 0 and ribavirin trough concentration during the first three months of therapy were correlated with sustained virological response (SVR. These studies highlighted the relevance of ribavirin pharmacologic monitoring and early dose adaptation during therapy. Although the role of ribavirin within new direct acting antiviral (DAA combinations will probably decrease in the future, its potential benefit in difficult-to-treat patients such as patients with severe hepatopathy or patients who failed triple therapy including patients with multiresistance will need to be further investigated.

  19. Characterization of DNA polymerase-associated acyclovir-resistant herpes simplex virus type 1: mutations, sensitivity to antiviral compounds, neurovirulence, and in-vivo sensitivity to treatment.

    Science.gov (United States)

    Wang, Li-Xin; Takayama-Ito, Mutsuyo; Kinoshita-Yamaguchi, Hitomi; Kakiuchi, Satsuki; Suzutani, Tatsuo; Nakamichi, Kazuo; Lim, Chang-Kweng; Kurane, Ichiro; Saijo, Masayuki

    2013-01-01

    Acyclovir (ACV)-resistant (ACV(r)) mutants were generated from plaque-purified ACV-sensitive herpes simplex virus type 1 (HSV-1) by culturing the virus in Vero cells in the presence of 2-amino-7-(1,3-dihydroxy-2-propoxymethyl) purine (S2242). Three DNA polymerase (DNApol)-associated ACV(r) HSV-1 generated under ACV selection in a previous study (Suzutani, T., Ishioka, K., De Clercq, E., et al., Antimicrob. Agents Chemother., 47, 1707-1713, 2003) were also included. The sensitivity of the mutants to other antivirals and their neurovirulence were determined. The treatment efficacy of ACV and ganciclovir (GCV) against ACV(r) HSV-1 infections was evaluated in mice. Amino acid substitutions were demonstrated in conserved regions II and III in DNApol in 5 of the 6 mutants, while the other substitution was located in non-conserved regions. DNApol-associated ACV(r) clones showed cross-resistance to foscarnet, penciclovir, and vidarabine but were sensitive or hypersensitive to GCV, brivudin, sorivudine, and spongothymidine. The ACV(r) clone with an N815S mutation in DNApol showed similar neurovirulence to that of the parent virus; however, those with other mutations showed attenuation. GCV was effective in the treatment of the ACV(r) clone with similar virulence to that of parent HSV-1, while ACV was less effective in mice. These results indicate the importance of the characterization of HSV-1 isolates for the proper treatment of HSV-1 infections exhibiting ACV-resistance.

  20. Clinical observation of serum IL-18, IL-10 and sIL-2R levels in patients with chronic hepatitis C pre- and post antiviral treatment

    Institute of Scientific and Technical Information of China (English)

    贾红宇; 杜杰; 朱思和; 马英骥; 蔡华枫

    2003-01-01

    Objective To discuss the roles of serum interleukin-18 (IL-18), interleukin-10 (IL-10) and soluble interleukin-2R (sIL-2R) in the pathogenesis of chronic hepatitis C and to observe the effects of interferon (IFN) on the above- mentioned serum cytokines. Methods The levels of above- mentioned cytokines were detected in 10 healthy individuals, 24 asymptomatic hepatitis virus C (HCV) carriers and 27 patients with chronic hepatitis C ( before and after IFN treatment) using enzyme linked immunosorbent assay (ELISA). Results The levels of the cytokines in patients with chronic hepatitis C are higher than in healthy people (P<0.05) and in asymptomatic HCV carriers(P<0.05). The values of the cytokines show a significant positive correlation to ALT (P<0.05). Levels of tested cytokines decreased observably after IFN treatment (P<0.05). The grades of the serum levels for sIL-2R and IL-10 before IFN treatment (from high to low) were categorized accordingly: non-response group> partial- response group >complete- response group (P<0.05). Conclusions The tested cytokines co-participate in the pathogenesis of chronic hepatitis C, and can be used to evaluate the effect of IFN on the immune state of organisms. Furthermore, sIL-2R and IL-10 are important for predicting the anti-viral efficacy of IFN.

  1. Diagnosis of septic arthritis and initial antibiotic treatment

    OpenAIRE

    Bombaci, Hasan; Canbora, Kerem; Onur, Gokhan; Gorgec, Mucahit; Dosoglu, Nilgun

    2004-01-01

    Objectives: This study was designed to determine the similarities and differences in clinical, laboratory and radiographic presentation of septic arthritis in childhood and at adult ages, to find out its etiological profile, and to establish an antibiotic treatment protocol for the initial period and for patients in whom the causative agent could not be identified. Methods: Thirty-four patients (age range 15 months to 85 years) who underwent surgery with a diagnosis of septic arthritis wer...

  2. Baseline quasispecies selection and novel mutations contribute to emerging resistance-associated substitutions in hepatitis C virus after direct-acting antiviral treatment

    Science.gov (United States)

    Kai, Yugo; Hikita, Hayato; Morishita, Naoki; Murai, Kazuhiro; Nakabori, Tasuku; Iio, Sadaharu; Hagiwara, Hideki; Imai, Yasuharu; Tamura, Shinji; Tsutsui, Syusaku; Naito, Masafumi; Nishiuchi, Meiko; Kondo, Yasuteru; Kato, Takanobu; Suemizu, Hiroshi; Yamada, Ryoko; Oze, Tsugiko; Yakushijin, Takayuki; Hiramatsu, Naoki; Sakamori, Ryotaro; Tatsumi, Tomohide; Takehara, Tetsuo

    2017-01-01

    Resistance-associated substitutions (RASs) in hepatitis C virus (HCV) appear upon failure of treatment with direct-acting antivirals (DAAs). However, their origin has not been clarified in detail. Among 11 HCV genotype 1b patients who experienced virologic failure with asunaprevir (ASV)/daclatasvir (DCV), 10 had major NS5A L31M/V-Y93H variants after treatment. L31M/V-Y93H variants were detected as a minor clone before therapy in 6 patients and were the most closely related to the post-treatment variants by phylogenetic tree analysis in 4 patients. Next, to consider the involvement of a trace amount of pre-existing variants below the detection limit, we analysed human hepatocyte chimeric mice infected with DAA-naïve patient serum. L31V-Y93H variants emerged after treatment with ledipasvir (LDV)/GS-558093 (nucleotide NS5B inhibitor) and decreased under the detection limit, but these variants were dissimilar to the L31V-Y93H variants reappearing after ASV/DCV re-treatment. Finally, to develop an infection derived from a single HCV clone, we intrahepatically injected full-genome HCV RNA (engineered based on the wild-type genotype 1b sequence) into chimeric mice. A new Y93H mutation actually occurred in this model after LDV monotherapy failure. In conclusion, post-treatment RASs appear by 2 mechanisms: the selection of pre-existing substitutions among quasispecies and the generation of novel mutations during therapy. PMID:28134353

  3. CpG oligodeoxynucleotide-specific goose TLR21 initiates an anti-viral immune response against NGVEV but not AIV strain H9N2 infection.

    Science.gov (United States)

    Qi, Yulin; Yan, Bing; Chen, Shun; Chen, Hongjun; Wang, Mingshu; Jia, Renyong; Zhu, Dekang; Liu, Mafeng; Liu, Fei; Yang, Qiao; Sun, Kunfeng; Wu, Ying; Chen, Xiaoyue; Jing, Bo; Cheng, Anchun

    2016-03-01

    Toll-like receptors (TLRs) recognize components of pathogens and mediate the host innate immune response. TLR21 is a TLR that specifically recognizes exogenous double-stranded DNA and rapidly signals to downstream innate immune factors. This study reports the cDNA of goose TLR21 and identifies its immune characteristics. The goose TLR21 is 3161 base pairs and encodes a 975 amino acid protein. As predicted, the goose transmembrane protein TLR21 has a signal peptide, leucine-rich repeat regions, a transmembrane domain, and a Toll/interleukin-1 receptor domain. Multiple sequence alignments and phylogenetic analyses showed that goose TLR21 has homology to chicken TLR21. The tissue distribution of TLR21 suggested that it has high transcript levels in immune-associated tissues, especially in the bursa of Fabricius, the Hadrian gland, and the thymus. After challenge with agonist ODN2006 and new type gosling viral enteritis virus (NGVEV), significant induction of TLR21 production, pro-inflammatory cytokines IL-1β and IL-6, and interferons were observed in peripheral blood mononuclear cells. Both synthetic DNA (ODN2006) and viral DNA (NGVEV) can be recognized by goose TLR21, which leads to a rapid up-regulation of pro-inflammatory cytokines and anti-viral molecules. In vivo, avian influenza A virus H9N2 and NGVEV were used to infect goslings, which was followed by a significant up-regulation of TLR21 mRNA transcripts in multiple tissues of NGVEV-infected geese. In general, goose TLR21 plays an important role in binding invading pathogenic DNA viruses, which subsequently triggers an innate immune response; furthermore, it acts as a functional homologue of mammalian TLR9, as TLR21 recognizes a mammalian TLR9 agonist.

  4. 75 FR 11189 - Expanded Access to Direct-Acting Antiviral Agents for the Treatment of Chronic Hepatitis C...

    Science.gov (United States)

    2010-03-10

    ... Treatment of Chronic Hepatitis C Infection in Patients With Unmet Medical Need; Public Hearing; Request for... agents (DAAs) for the treatment of chronic hepatitis C (CHC) infection in patients with unmet medical... . SUPPLEMENTARY INFORMATION: I. Background A. CHC In the United States, hepatitis C virus infection causes...

  5. Improvement of quantitative testing of liver function in patients with chronic hepatitis C after installment of antiviral therapy

    Institute of Scientific and Technical Information of China (English)

    Matthias Ocker; Marion Ganslmayer; Steffen Zopf; Susanne Gahr; Christopher Janson; Eckhart G. Hahn; Christoph Herold

    2005-01-01

    AIM: To investigate if and to what extent antiviral therapy influenced a broad panel of quantitative testing of liver function (QTLF).METHODS: Fifty patients with chronic hepatitis C were either treated with interferon (n = 8), interferon/ribavirin (n = 19) or peg-interferon/ribavirin (n = 23). Quantitative testing of liver function, including aminopyrine breath test (ABT), galactose elimination capacity (GEC), sorbitol clearance (SCI) and indocyanine green clearance (ICG)was performed before and 3 mo after initiation of antiviral therapy.RESULTS: After 3 mo of antiviral treatment, 36 patients showed normal transaminases and were negative for HCV-RNA, 14 patients did not respond to therapy. ABT and GEC as parameters of microsomal and cytosolic liver function were reduced in all patients before therapy initiation and returned to normal values in the 36 therapy responders after 3 mo. Parameters of liver perfusion (SCI and ICG) were not affected by antiviral therapy. In the 14 non-responders,no changes in QTLF values were observed during the treatment period.CONCLUSION: ICG and SCI remained unaffected in patients with chronic hepatitis C, while ABT and GEC were significantly compromised. ABT and GEC normalized in responders to antiviral therapy. Early determination of ABT and GEC may differentiate responders from non-responders to antivJral treatment in hepatitis C.

  6. Direct-acting Antiviral Agents Resistance-associated Polymorphisms in Chinese Treatment-na(i)ve Patients Infected with Genotype 1b Hepatitis C Virus

    Institute of Scientific and Technical Information of China (English)

    Ye Wang; Hui-Ying Rao; Xing-Wang Xie; Lai Wei

    2015-01-01

    Background:It has been reported that several baseline polymorphisms of direct-acting antivirals (DAAs) agents resistance-associated variants (RAVs) would affect the treatment outcomes of patients chronically infected with hepatitis C virus (CHC).The aim of this study is to investigate the prevalence of DAAs RAVs in treatment-na(i)ve GT1b CHC patients.Methods:Direct sequencing and ultra-deep sequencing of the HCV NS3,NS5A,and NS5B gene were performed in baseline serum samples of treatment-ha(i)ve patients infected with genotype lb hepatitis C virus (HCVs).Results:One hundred and sixty CHC patients were studied.Complete sequence information was obtained for 145 patients (NS3),148 patients (NS5A),and 137 patients (NS5B).Treatment-failure associated variants of DAAs were detected:56.6% (82/145) of the patients presented S122G for simeprevir (NS3 protease inhibitor);10.1% (14/148) of the patients presented Y93H for daclatasvir and ledipasvir (NS5A protein inhibitors);94.2% (129/137) of the patients presented C316N for sofosbuvir (NS5B polymerase inhibitor).Nearly,all of the DAAs RAVs detected by ultra-deep sequencing could be detected by direct sequencing.Conclusions:The majority of genotype lb CHC patients in China present a virus population carrying HCV DAAs RAVs.Pretreatment sequencing of HCV genome might need to be performed when patients infected with GTlb HCV receiving DAAs-containing regimens in China.Population sequencing would be quite quantified for the work.

  7. Geno2pheno[HCV] - A Web-based Interpretation System to Support Hepatitis C Treatment Decisions in the Era of Direct-Acting Antiviral Agents.

    Directory of Open Access Journals (Sweden)

    Prabhav Kalaghatgi

    Full Text Available The face of hepatitis C virus (HCV therapy is changing dramatically. Direct-acting antiviral agents (DAAs specifically targeting HCV proteins have been developed and entered clinical practice in 2011. However, despite high sustained viral response (SVR rates of more than 90%, a fraction of patients do not eliminate the virus and in these cases treatment failure has been associated with the selection of drug resistance mutations (RAMs. RAMs may be prevalent prior to the start of treatment, or can be selected under therapy, and furthermore they can persist after cessation of treatment. Additionally, certain DAAs have been approved only for distinct HCV genotypes and may even have subtype specificity. Thus, sequence analysis before start of therapy is instrumental for managing DAA-based treatment strategies. We have created the interpretation system geno2pheno[HCV] (g2p[HCV] to analyse HCV sequence data with respect to viral subtype and to predict drug resistance. Extensive reviewing and weighting of literature related to HCV drug resistance was performed to create a comprehensive list of drug resistance rules for inhibitors of the HCV protease in non-structural protein 3 (NS3-protease: Boceprevir, Paritaprevir, Simeprevir, Asunaprevir, Grazoprevir and Telaprevir, the NS5A replicase factor (Daclatasvir, Ledipasvir, Elbasvir and Ombitasvir, and the NS5B RNA-dependent RNA polymerase (Dasabuvir and Sofosbuvir. Upon submission of up to eight sequences, g2p[HCV] aligns the input sequences, identifies the genomic region(s, predicts the HCV geno- and subtypes, and generates for each DAA a drug resistance prediction report. g2p[HCV] offers easy-to-use and fast subtype and resistance analysis of HCV sequences, is continuously updated and freely accessible under http://hcv.geno2pheno.org/index.php. The system was partially validated with respect to the NS3-protease inhibitors Boceprevir, Telaprevir and Simeprevir by using data generated with recombinant

  8. Direct-acting antiviral treatment in adults infected with hepatitis C virus: Reactivation of hepatitis B virus coinfection as a further challenge.

    Science.gov (United States)

    De Monte, Anne; Courjon, Johan; Anty, Rodolphe; Cua, Eric; Naqvi, Alissa; Mondain, Véronique; Cottalorda, Jacqueline; Ollier, Laurence; Giordanengo, Valérie

    2016-05-01

    Use of direct-acting antiviral drugs (DAAs) greatly improves management of adults infected with hepatitis C virus (HCV) whether patients are treatment-naive or unsuccessfully pre-treated. Several inhibitors of viral nonstructural proteins (NS3/4A protease, NS5A and NS5B polymerase) allow a rapid HCV clearance and increase rates of sustained virological response. Both the EASL and AASLD guidelines have recently published up-to-date recommendations for their use, addressing each HCV genotype and particular situations. However, management of patients coinfected with hepatitis B virus (HBV) has been developed by these guidelines with reference to cases of HBV reactivation reported during previous anti-HCV regimens containing interferon known active against both HBV and HCV. In the setting of the interferon-free HCV therapies with DAAs only, the possibility of HBV reactivation during treatment of hepatitis C is raised due to viral interferences in HCV/HBV coinfected persons. Herein, we report a case of early HBV reactivation during DAAs-based anti-HCV treatment (ledipasvir/sofosbuvir) in a patient having a resolved HBV infection and chronically infected with HCV genotype 4 and HIV. Moreover, we review similar recent cases of HBV reactivation in patients infected with HBV and HCV genotype 1 during treatment of hepatitis C by regimen incorporating other combination of DAAs (sofosbuvir/simeprevir or daclatasvir/asunaprevir). Due to the potential risk of early HBV reactivation in HCV/HBV-coinfected patients during interferon-free DAAs-based HCV therapies, altogether these cases highlight the necessity to closely monitor HBV coinfection, regardless its stage (chronic, occult, resolved), whatever HCV genotype or class of DAAs used.

  9. New strategies for the treatment of hepatitis C virus infection and implications of resistance to new direct-acting antiviral agents

    Directory of Open Access Journals (Sweden)

    Josep Quer

    2010-11-01

    Full Text Available Josep Quer1–3, Maria Buti1–3, Maria Cubero1–3, Jaume Guardia1–3, Rafael Esteban1–3, Juan Ignacio Esteban1–31Liver Unit, Internal Medicine Hospital Universitari Vall d’Hebron, Institut de Recerca (VHIR, Barcelona, Spain; 2Universitat Autònoma de Barcelona, Barcelona, Spain; 3Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd, Instituto de Salud Carlos III, Madrid, SpainAbstract: Persistent hepatitis C virus (HCV infection is a leading cause of chronic hepatitis, cirrhosis, and hepatocellular carcinoma and the major indication for liver transplantation in adults. Current standard of care treatment (SOC with pegylated-interferon-a 2 and ribavirin (RBV has a limited efficacy and is associated with significant side effects frequently associated with poor compliance or treatment discontinuation, requiring specialized and frequent monitoring. To overcome the limited efficacy of SOC, more than 50 direct-acting antiviral agents (DAA designed to target viral-encoded proteins essential in the HCV life cycle are currently under development. The rapid selection of resistant mutants associated with the quasispecies nature of HCV with high mutation and replication rates is one of the main challenges for the new HCV therapies. Predictive host and viral factors together with combination of DAAs with or without IFN and/or RBV need to be accurately evaluated to design the most effective individualized treatment strategy within the shortest time interval and with minimum side effects.Keywords: HCV, treatment, quasispecies, resistance

  10. Geno2pheno[HCV] – A Web-based Interpretation System to Support Hepatitis C Treatment Decisions in the Era of Direct-Acting Antiviral Agents

    Science.gov (United States)

    Kalaghatgi, Prabhav; Sikorski, Anna Maria; Knops, Elena; Rupp, Daniel; Sierra, Saleta; Heger, Eva; Neumann-Fraune, Maria; Beggel, Bastian; Walker, Andreas; Timm, Jörg; Walter, Hauke; Obermeier, Martin; Kaiser, Rolf; Bartenschlager, Ralf; Lengauer, Thomas

    2016-01-01

    The face of hepatitis C virus (HCV) therapy is changing dramatically. Direct-acting antiviral agents (DAAs) specifically targeting HCV proteins have been developed and entered clinical practice in 2011. However, despite high sustained viral response (SVR) rates of more than 90%, a fraction of patients do not eliminate the virus and in these cases treatment failure has been associated with the selection of drug resistance mutations (RAMs). RAMs may be prevalent prior to the start of treatment, or can be selected under therapy, and furthermore they can persist after cessation of treatment. Additionally, certain DAAs have been approved only for distinct HCV genotypes and may even have subtype specificity. Thus, sequence analysis before start of therapy is instrumental for managing DAA-based treatment strategies. We have created the interpretation system geno2pheno[HCV] (g2p[HCV]) to analyse HCV sequence data with respect to viral subtype and to predict drug resistance. Extensive reviewing and weighting of literature related to HCV drug resistance was performed to create a comprehensive list of drug resistance rules for inhibitors of the HCV protease in non-structural protein 3 (NS3-protease: Boceprevir, Paritaprevir, Simeprevir, Asunaprevir, Grazoprevir and Telaprevir), the NS5A replicase factor (Daclatasvir, Ledipasvir, Elbasvir and Ombitasvir), and the NS5B RNA-dependent RNA polymerase (Dasabuvir and Sofosbuvir). Upon submission of up to eight sequences, g2p[HCV] aligns the input sequences, identifies the genomic region(s), predicts the HCV geno- and subtypes, and generates for each DAA a drug resistance prediction report. g2p[HCV] offers easy-to-use and fast subtype and resistance analysis of HCV sequences, is continuously updated and freely accessible under http://hcv.geno2pheno.org/index.php. The system was partially validated with respect to the NS3-protease inhibitors Boceprevir, Telaprevir and Simeprevir by using data generated with recombinant, phenotypic

  11. Importance of proper initial treatment of moderate and major burns

    Directory of Open Access Journals (Sweden)

    Vulović Dejan

    2008-01-01

    Full Text Available Background/Aim. Burns are common injuries with frequency depending on human factors, development of protection, industry and traffic, eventual wars. Organized treatment of major burn injuries has tremendous medical, social and economic importance. The aim of this study was to analyze initial treatment of major and moderate burns, to compare it with the current recommendations and to signify the importance of organized management of burns. Methods. In a prospective study 547 adult patients with major burns were analyzed, covering a period of eight years, with the emphasis on the initial hospital admission and emergency care for burns greater than 10% of total body surface area (TBSA. Results. In the different groups of major burns, the percentage of hospital admission was: 81.5 in burns greater than 10% TBSA, 37.7 in burns of the functional areas, 54.5 in the III degree burns, 81.6 in electrical burns, 55.9 in chemical burns, 61.9 in inhalation injury, 41.0 in burns in patients with the greater risk and 100 in burns with a concomitant trauma. In the group of 145 patients with burns greater than 10% TBSA, intravenous fluids were given in 87 patients, analgesics in 45, corticosteroids in 29, antibiotics in 23 and oxygen administration in 14. In the same group, wound irrigation was done in 14.4%, removing of the clothing and shoes in 29.6%, elevation of the legs in 8.9% and prevention of hypothermia in 7.6% of the victims. There were no initial estimations of burn extent (percentage of a burn, notes about the patient and injury and tetanus immunizations. Conclusion. Based on these findings, it is concluded that there should be much more initial hospital admissions of major burns, and also, necessary steps in the emergency care of burns greater than 10% TBSA should be taken more frequently. On the other side, unnecessary or wrong steps should be avoided in the initial burn treatment.

  12. Is sustained virological response a marker of treatment efficacy in patients with chronic hepatitis C viral infection with no response or relapse to previous antiviral intervention?

    DEFF Research Database (Denmark)

    Gurusamy, Kurinchi S; Wilson, Edward; Koretz, Ronald L

    2013-01-01

    Randomised clinical trials (RCTs) of antiviral interventions in patients with chronic hepatitis C virus (HCV) infection use sustained virological response (SVR) as the main outcome. There is sparse information on long-term mortality from RCTs....

  13. Novel composite efficacy measure to demonstrate the rationale and efficacy of combination antiviral-anti-inflammatory treatment for recurrent herpes simplex labialis.

    Science.gov (United States)

    Hull, Christopher M; Levin, Myron J; Tyring, Stephen K; Spruance, Spotswood L

    2014-01-01

    Historically, the primary target for research and treatment of recurrent herpes simplex labialis (HSL) has been limited to inhibiting herpes simplex virus (HSV) replication. Antiviral monotherapy, however, has proven only marginally effective in curtailing the duration and severity of recurrent lesions. Recently, the role of inflammation in the progression and resolution of recurrences has been identified as an additional target. This was evaluated in a randomized study comparing combination topical 5% acyclovir-1% hydrocortisone cream (AHC) with 5% acyclovir alone (AC; in the AHC vehicle) and the vehicle. The efficacy of each topical therapy was evaluated for cumulative lesion size--a novel composite efficacy endpoint incorporating episode duration, lesion area, and proportion of nonulcerative lesions. In that study, cumulative lesion area was significantly decreased with AHC compared with AC (25% decrease; P<0.05) and the vehicle (50% decrease; P<0.0001). As research continues in this arena, cumulative lesion area should be included as a measure of efficacy in clinical trials of recurrent HSL therapies.

  14. Anti-viral drug treatment along with immune activator IL-2: a control-based mathematical approach for HIV infection

    Science.gov (United States)

    Nath Chatterjee, Amar; Roy, Priti Kumar

    2012-02-01

    Recent development in antiretroviral treatment against HIV can help AIDS patients to fight against HIV. But the question that whether the disease is to be partially or totally eradicated from HIV infected individuals still remains unsolved. Usually, the most effective treatment for the disease is HAART which can only control the disease progression. But as the immune system becomes weak, the patients can not fight against other diseases. Immune cells are activated and proliferated by IL-2 after the identification of antigen. IL-2 production is impaired in HIV positive patients and intermitted administration of immune activator IL-2 together with HAART which is a more effective treatment to fight against the disease. Thus, its expediency is essential and is yet to be explored. In this article we anticipated a mathematical model of the effect of IL-2 together with RTIs therapy in HIV positive patients. Our analytical as well as numerical study shows that the optimal schedule of treatment for best result is to be obtained by systematic drug therapy. But at the last stage of treatment, the infection level raises again due to minimisation of drug dosage. Thus we study the perfect adherence of the drugs and found out if RTIs are taken with sufficient interval then for fixed interval of IL-2 therapy, certain amount of drug dosages may be able to sustain the immune system at pre-infection stage and the infected CD4+T cells are going towards extinction.

  15. Rapid Virological Response Represents the Highest Prediction Factor of Response to Antiviral Treatment in HCV-Related Chronic Hepatitis: a Multicenter Retrospective Study

    Directory of Open Access Journals (Sweden)

    Federico

    2015-06-01

    Full Text Available Background Standard [i.e. pegylated interferon (Peg-IFN + ribavirin] treatment of hepatitis C virus (HCV-related chronic hepatitis is associated with a sustained virological response (SVR in 50 - 90% of patients. A rapid virological response (RVR (i.e. negative HCV-RNA after 4 weeks of treatment predicts SVR in almost 90% of patients. Objectives The main aim of this study was to assess the strength of RVR, as a predictive factor of antiviral treatment response. Patients and Methods Using univariate and multivariate analysis, we retrospectively evaluated biochemical, metabolic, genetic and viral variables that might affect both RVR and SVR to Peg-IFN plus ribavirin, in 315 consecutive outpatients affected by HCV-related chronic hepatitis. Results At univariate analysis, staging, body mass index, RVR, genotype and viral load were significantly related to SVR (P < 0.001. At multivariate analysis, RVR and genotype remained significant (P < 0.00001. The RVR had a predictive value of 83%. At univariate and multivariate analyses, diabetes (P = 0.003, genotype 2 (P = 0.000 and HCV-RNA values (P = 0.016 were independent predictors of RVR, even though at multivariate analyses, only genotype 2 was significantly related to RVR. When we stratified patients, according to genotype, no laboratory or clinical factors were predictive of RVR in genotype 1 patients at either univariate or multivariate analysis. In genotype 2 patients, staging (P = 0.029 and diabetes (P = 0.001 were the only significant predictors of RVR at univariate analyses, whereas no factor was independently related to RVR, at multivariate analysis. Conclusions The RVR is the strongest factor of SVR and infection with HCV genotype 2 is significantly associated with RVR. Neither biochemical and/or metabolic factors seem to exert influence on RVR.

  16. Colitis during new direct-acting antiviral agents (DAAs) therapy with sofosbuvir, simeprevir and ribavirin for genotype 1b hepatitis C.

    Science.gov (United States)

    Izzo, Ilaria; Zanotti, Paola; Chirico, Claudia; Casari, Salvatore; Villanacci, Vincenzo; Salemme, Marianna; Biasi, Luciano; Festa, Elena; Castelli, Francesco

    2016-12-01

    Since 2014 several direct-acting antivirals (DAAs) have been made available, allowing interferon-free antiviral treatments with high sustained virological response rates. Side effects are, however, a real challenge during treatment. Sarkar et al. recently published a case of colitis following initiation of sofosbuvir and simeprevir for genotype 1 hepatitis C. We report the case of a patient with no prior history of inflammatory bowel disease, who developed significant bloody diarrhea within 3 weeks of sofosbuvir/simeprevir/ribavirin initiation. Colonoscopy and biopsy suggested a drug-induced colitis.

  17. Efficacy of Second Generation Direct-Acting Antiviral Agents for Treatment Naive Hepatitis C Genotype 1: A Systematic Review and Network Meta-Analysis.

    Directory of Open Access Journals (Sweden)

    Thanthima Suwanthawornkul

    Full Text Available The treatment of hepatitis C (HCV infections has significantly changed in the past few years due to the introduction of direct-acting antiviral agents (DAAs. DAAs could improve the sustained virological response compared to pegylated interferon with ribavirin (PR. However, there has been no evidence from randomized controlled trials (RCTs that directly compare the efficacy among the different regimens of DAAs.Therefore, we performed a systematic review and network meta-analysis aiming to compare the treatment efficacy between different DAA regimens for treatment naïve HCV genotype 1.Medline and Scopus were searched up to 25th May 2015. RCTs investigating the efficacy of second generation DAA regimens for treatment naïve HCV genotype 1 were eligible for the review. Due to the lower efficacy and more side effects of first generation DAAs, this review included only second generation DAAs approved by the US or EU Food and Drug Administration, that comprised of simeprevir (SMV, sofosbuvir (SOF, daclatasvir (DCV, ledipasvir (LDV, and paritaprevir/ritonavir/ombitasvir plus dasabuvir (PrOD. Primary outcomes were sustained virological response at weeks 12 (SVR12 and 24 (SVR24 after the end of treatment and adverse drug events (i.e. serious adverse events, anemia, and fatigue. Efficacy of all treatment regimens were compared by applying a multivariate random effect meta-analysis. Incidence rates of SVR12 and SVR24, and adverse drug events of each treatment regimen were pooled using 'pmeta' command in STATA program.Overall, 869 studies were reviewed and 16 studies were eligible for this study. Compared with the PR regimen, SOF plus PR, SMV plus PR, and DVC plus PR regimens yielded significantly higher probability of having SVR24 with pooled risk ratios (RR of 1.98 (95% CI 1.24, 3.14, 1.46 (95% CI: 1.22, 1.75, and 1.68 (95% CI: 1.14, 2.46, respectively. Pooled incidence rates of SVR12 and SVR24 in all treatment regimens without PR, i.e. SOF plus LDV with

  18. Initial experience with ocriplasmin in the treatment of vitreomacular traction

    Directory of Open Access Journals (Sweden)

    José Maurício Botto de Barros Garcia

    2016-04-01

    Full Text Available ABSTRACT This study aimed to report the clinical and structural outcomes of intravitreal ocriplasmin in the treatment of vitreomacular interface disorders in two tertiary centers in Brazil. A retrospective study was performed by reviewing medical records and spectral domain optical coherence tomography (SD-OCT findings of seven patients who were treated with a single ocriplasmin injection. A total of 57.14% of patients achieved resolution of vitreomacular traction as evidenced by SD-OCT. Regarding our functional results, 87.71% maintained or improved visual acuity after follow-up. To the best of our knowledge, this is the first study reporting initial results of ocriplasmin therapy in Brazil.

  19. Dasatinib and Doxorubicin Treatment of Sarcoma Initiating Cells

    DEFF Research Database (Denmark)

    Aggerholm-Pedersen, Ninna; Demuth, Christina; Safwat, Akmal;

    2016-01-01

    ) treatment with or without doxorubicin was assessed by MTS assay. Results. Initial results showed that the hMSC-TERT4 was more doxorubicin-sensitive while hMSC-TERT20-CE8 was less doxorubicin-sensitive evidenced by monitoring cell viability in the presence of doxorubicin at different doses. The epidermal......) stem cell line hMSC-TERT4 and a transformed cell line hMSC-TERT20-CE8, known to form sarcoma-like tumours when implanted in immune-deficient mice, were used as models. Receptor tyrosine kinase (RTK) activation was analysed by RTK arrays and cellular viability after tyrosine kinases inhibitor (TKI...... growth factor receptor (EGFR) was activated in both cell lines. However hMSC-TERT20-CE8 exhibited significantly higher expression of the EGFR ligands. EGFR inhibitors such as erlotinib and afatinib alone or in combination with doxorubicin failed to further decrease cell viability of hMSC-TERT20-CE8...

  20. Markedly Improved Glycemic Control in Poorly Controlled Type 2 Diabetes following Direct Acting Antiviral Treatment of Genotype 1 Hepatitis C

    Directory of Open Access Journals (Sweden)

    Raymond Anthony Pashun

    2016-01-01

    Full Text Available Type 2 diabetes mellitus (T2DM is often associated with hepatitis C virus (HCV infection. Successful HCV treatment may improve glycemic control and potentially induce remission of T2DM. We report a case of an obese 52-year-old woman with mixed genotype 1a/1b HCV infection with compensated cirrhosis and a 10-year history of poorly controlled T2DM on insulin therapy. Following successful therapy with sofosbuvir, simeprevir, and ribavirin, her insulin requirements decreased and her glycosylated hemoglobin (HgA1c normalized despite weight gain. This case suggests an association between HCV and T2DM and the potential for significant improvement in glycemic control with eradication of HCV.

  1. Systems biology: A tool for charting the antiviral landscape.

    Science.gov (United States)

    Bowen, James R; Ferris, Martin T; Suthar, Mehul S

    2016-06-15

    The host antiviral programs that are initiated following viral infection form a dynamic and complex web of responses that we have collectively termed as "the antiviral landscape". Conventional approaches to studying antiviral responses have primarily used reductionist systems to assess the function of a single or a limited subset of molecules. Systems biology is a holistic approach that considers the entire system as a whole, rather than individual components or molecules. Systems biology based approaches facilitate an unbiased and comprehensive analysis of the antiviral landscape, while allowing for the discovery of emergent properties that are missed by conventional approaches. The antiviral landscape can be viewed as a hierarchy of complexity, beginning at the whole organism level and progressing downward to isolated tissues, populations of cells, and single cells. In this review, we will discuss how systems biology has been applied to better understand the antiviral landscape at each of these layers. At the organismal level, the Collaborative Cross is an invaluable genetic resource for assessing how genetic diversity influences the antiviral response. Whole tissue and isolated bulk cell transcriptomics serves as a critical tool for the comprehensive analysis of antiviral responses at both the tissue and cellular levels of complexity. Finally, new techniques in single cell analysis are emerging tools that will revolutionize our understanding of how individual cells within a bulk infected cell population contribute to the overall antiviral landscape.

  2. Self-interest versus group-interest in antiviral control

    NARCIS (Netherlands)

    Boven, M. van; Klinkenberg, D.; Pen, I.; Weissing, F.J.; Heesterbeek, J.A.P.

    2008-01-01

    Antiviral agents have been hailed to hold considerable promise for the treatment and prevention of emerging viral diseases like H5N1 avian influenza and SARS. However, antiviral drugs are not completely harmless, and the conditions under which individuals are willing to participate in a large-scale

  3. Ophthalmic antiviral chemotherapy : An overview

    Directory of Open Access Journals (Sweden)

    Athmanathan Sreedharan

    1997-01-01

    Full Text Available Antiviral drug development has been slow due to many factors. One such factor is the difficulty to block the viral replication in the cell without adversely affecting the host cell metabolic activity. Most of the antiviral compounds are analogs of purines and pyramidines. Currently available antiviral drugs mainly inhibit viral nucleic acid synthesis, hence act only on actively replicating viruses. This article presents an overview of some of the commonly used antiviral agents in clinical ophthalmology.

  4. Antiviral Drugs: Seasonal Flu

    Centers for Disease Control (CDC) Podcasts

    2010-09-29

    In this podcast, Dr. Joe Bresee explains the nature of antiviral drugs and how they are used for seasonal flu.  Created: 9/29/2010 by National Center for Immunization and Respiratory Diseases (NCIRD).   Date Released: 9/29/2010.

  5. Results of a Multinational Study Suggest the Need for Rapid Diagnosis and Early Antiviral Treatment at the Onset of Herpetic Meningoencephalitis

    DEFF Research Database (Denmark)

    Erdem, Hakan; Cag, Yasemin; Ozturk-Engin, Derya;

    2015-01-01

    Data in the literature regarding the factors that predict unfavorable outcomes in adult herpetic meningoencephalitis (HME) cases are scarce. We conducted a multicenter study in order to provide insights into the predictors of HME outcomes, with special emphasis on the use and timing of antiviral ...

  6. Concordance of sustained virologic response at weeks 4, 12 and 24 post-treatment of hepatitis c in the era of new oral direct-acting antivirals: A concise review.

    Science.gov (United States)

    Burgess, Sarah V; Hussaini, Trana; Yoshida, Eric M

    2016-01-01

    The goal of treatment for chronic hepatitis C viral (HCV) infection is to cure the infection rather than suppress the virus. Historically, a sustained virological response (SVR) defined as undetectable HCV RNA at 24 weeks following the completion of treatment was considered the gold standard to define successful eradication of the virus as a primary endpoint in clinical trials. SVR measured at 12 weeks post-treatment has been shown to be highly concordant with SVR24 in trials of pegylated interferon and ribavirin. The appropriateness and durability of SVR12 as the efficacy endpoint with new oral direct-acting antivirals is less established. A literatura search was performed using PubMed, EMBASE and CENTRAL databases to identify any studies that examined the concordance between SVR24 and earlier time points. Two studies and 4 abstracts were found that performed concordance analyses using positive and negative predictive values. Overall, SVR4 and SVR12 were highly concordant with SVR24 with high positive (> 97%) and negative (> 94%) predictive values; however there was a higher risk of HCV relapse occurring after post-treatment week 4. The majority of the data focused on SVR12 and demonstrated that SVR12 reliably predicted SVR24 in several populations infected with HCV (treatment-naïve, prior null responders, different genotypes) using various new oral direct-acting antiviral regimens. In conclusion, the available data suggests that SVR12 is a reliable assessment of HCV eradication and could be used instead of SVR24 for drug development clinical trials assessing efficacy of new direct-acting antivirals. Data on the long-term durability of SVR12 is still needed.

  7. Two-year treatment patterns and costs in glaucoma patients initiating treatment with prostaglandin analogs

    Directory of Open Access Journals (Sweden)

    Jordana K Schmier

    2010-09-01

    Full Text Available Jordana K Schmier1, Edmund C Lau2, David W Covert31Exponent, Alexandria, VI, USA; 2Exponent, Menlo Park, CA, USA; 3Alcon Research Ltd, Fort Worth, TX, USAObjective: To determine treatment patterns and costs over a two-year period among new initiators of topical prostaglandin analogs in a managed care population by retrospective cohort analysis of an insurance claims database.Methods: Patients who initiated therapy with a prostaglandin analog between September 2006 and March 2007 were identified. The use of monotherapy and adjunctive therapies were compared by index prostaglandin. Days to initiation of adjunctive therapy and rates of glaucoma surgical procedures were also calculated. Medical costs (antiglaucoma medications and ophthalmic visits over the two-year period were estimated.Results: The analysis identified 5018 patients with at least one prostaglandin analog prescription (bimatoprost, n = 747; latanoprost, n = 1651; benzalkonium chloride (BAK-free travoprost, n = 203. The majority (51%–54% had repeat prescriptions. Among those with repeat prescriptions, 52% were female (not significant and mean age was 64 years (P < 0.01. Rates of adjunctive therapy use varied across groups (bimatoprost 51%, latanoprost 37%, and BAK-free travoprost 35%, P < 0.0001. Median and mean days to initiation of adjunctive therapy were 83 and 140 for bimatoprost, 101 and 181 for latanoprost, and 113 and 221 for BAK-free travoprost. Two-year medical costs were $3147, $2843, and $2557 for patients initiating treatment with bimatoprost, latanoprost, and BAK-free travoprost, respectively. Use of glaucoma surgical procedures across the treatment groups was similar over the two-year period.Conclusions: Over a two-year period, the rate and time to initiation of adjunctive therapy use, as well as medical costs, varied between index prostaglandins. However, the rate of glaucoma surgical interventions did not vary significantly across index medications.Keywords: costs

  8. Antiviral Perspectives for Chikungunya Virus

    Directory of Open Access Journals (Sweden)

    Deepti Parashar

    2014-01-01

    Full Text Available Chikungunya virus (CHIKV is a mosquito-borne pathogen that has a major health impact in humans and causes acute febrile illness in humans accompanied by joint pains and, in many cases, persistent arthralgia lasting for weeks to years. CHIKV reemerged in 2005-2006 in several parts of the Indian Ocean islands and India after a gap of 32 years, causing millions of cases. The re-emergence of CHIKV has also resulted in numerous outbreaks in several countries in the eastern hemisphere, with a threat to further expand in the near future. However, there is no vaccine against CHIKV infection licensed for human use, and therapy for CHIKV infection is still mainly limited to supportive care as antiviral agents are yet in different stages of testing or development. In this review we explore the different perspectives for chikungunya treatment and the effectiveness of these treatment regimens and discuss the scope for future directions.

  9. Clinical significance of anaemia in chronic hepatitis c on the combined antiviral therapy with pegylated

    Directory of Open Access Journals (Sweden)

    K. V. Zhdanov

    2011-01-01

    Full Text Available In order to study the effect of combination antiviral therapy for hemoglobin and red blood cells in patients with chronic hepatitis C were estimated absolute numbers of red blood parameters. To determine the relation between the content of red blood cells and hemoglobin at different stages of antiviral therapy with the initial clinical and laboratory  parameters (gender, age, body mass index, genotype, level of viremia, ALT, fibrosis, as well as the results of combined antiviral therapy. Established that the decrease in hemoglobin levels were observed more frequently than the decline in the number of erythrocytes (63,6% and 21,1% respectively. In addition, anemia that occurred during treatment of HCV patients with pegylated interferon-α, directly correlated with the rate of sustained virological response. The study established prognostic criteria, indicating the possible development of anemia in the background of anti-viral therapy: the female sex, BMI <20 kg/m2, 1 genotype of HCV.

  10. Dasatinib and Doxorubicin Treatment of Sarcoma Initiating Cells: A Possible New Treatment Strategy

    Directory of Open Access Journals (Sweden)

    Ninna Aggerholm-Pedersen

    2016-01-01

    Full Text Available Background. One of the major challenges affecting sarcoma treatment outcome, particularly that of metastatic disease, is resistance to chemotherapy. Cancer-initiating cells are considered a major contributor to this resistance. Methods. An immortalised nontransformed human stromal (mesenchymal stem cell line hMSC-TERT4 and a transformed cell line hMSC-TERT20-CE8, known to form sarcoma-like tumours when implanted in immune-deficient mice, were used as models. Receptor tyrosine kinase (RTK activation was analysed by RTK arrays and cellular viability after tyrosine kinases inhibitor (TKI treatment with or without doxorubicin was assessed by MTS assay. Results. Initial results showed that the hMSC-TERT4 was more doxorubicin-sensitive while hMSC-TERT20-CE8 was less doxorubicin-sensitive evidenced by monitoring cell viability in the presence of doxorubicin at different doses. The epidermal growth factor receptor (EGFR was activated in both cell lines. However hMSC-TERT20-CE8 exhibited significantly higher expression of the EGFR ligands. EGFR inhibitors such as erlotinib and afatinib alone or in combination with doxorubicin failed to further decrease cell viability of hMSC-TERT20-CE8. However, inhibition with the TKI dasatinib in combination with doxorubicin decreased cell viability of the hMSC-TERT20-CE8 cell line. Conclusion. Our results demonstrate that dasatinib, but not EGFR-directed treatment, can decrease cell viability of stromal cancer stem cells less sensitive to doxorubicin.

  11. Rationale for combination therapy as initial treatment for hypertension.

    Science.gov (United States)

    Giles, Thomas D

    2003-01-01

    Recent hypertension guidelines recommend initiating antihypertensive therapy with a combination of two or more agents in patients whose blood pressure exceeds their appropriate blood pressure goal by 20/10 mm Hg. This recommendation is based on the knowledge that the majority of patients with blood pressures of this magnitude will not achieve sufficient blood pressure reduction with monotherapy. Further, compared with high-dose monotherapy, combination therapy is often associated with fewer adverse effects and, for this reason, may improve patient adherence. Bringing patients to blood pressure goal quickly is likely to improve clinical outcomes. This article discusses the rationale for using combination antihypertensive therapy as initial therapy for high blood pressure in selected patients and reviews data from a study of 364 high-risk patients with Stage 2 hypertension in which a fixed-dose combination product (amlodipine besylate/benazepril HCl) proved more successful as initial therapy than high-dose monotherapy (amlodipine besylate) in reducing blood pressure.

  12. Antiviral effect of cationic compounds on bacteriophages

    Directory of Open Access Journals (Sweden)

    Mai Huong eChatain-Ly

    2013-03-01

    Full Text Available The antiviral activity of several cationic compounds - cetytrimethylammonium (CTAB, chitosan, nisin and lysozyme - was investigated on the bacteriophage c2 (DNA head and non-contractile tail infecting Lactococcus strains and the bacteriophage MS2 (F-specific RNA infecting E.coli. Firstly, these activities were evaluated in a phosphate buffer pH 7- 10 mM. The CTAB had a virucidal effect on the Lactococcus bacteriophages, but not on the MS2. After 1 min of contact with 0.125 mM CTAB, the c2 population was reduced from 6 log(pfu/mL to 1,5 log(pfu/mL and completely deactivated at 1 mM. On the contrary, chitosan inhibited the MS2 more than it did the bacteriophages c2. No antiviral effect was observed for the nisin or the lysozyme on bacteriophages after 1 min of treatment. A 1 and 2.5 log reduction was respectively observed for nisin and lysozyme when the treatment time increased (5 or 10 min. These results showed that the antiviral effect depended both on the virus and structure of the antimicrobial compounds. The antiviral activity of these compounds was also evaluated in different physico-chemical conditions and in complex matrices. The antiviral activity of CTAB was impaired in acid pH and with an increase of the ionic strength. These results might be explained by the electrostatic interactions between cationic compounds and negatively charged particles such as bacteriophages or other compounds in a matrix. Milk proved to be protective suggesting the components of food could interfere with antimicrobial compounds.

  13. Broad-spectrum antiviral agents

    Directory of Open Access Journals (Sweden)

    Jun-Da eZhu

    2015-05-01

    Full Text Available Development of highly effective, broad-spectrum antiviral agents is the major objective shared by the fields of virology and pharmaceutics. Antiviral drug development has focused on targeting viral entry and replication, as well as modulating cellular defense system. High throughput screening of molecules, genetic engineering of peptides, and functional screening of agents have identified promising candidates for development of optimal broad-spectrum antiviral agents to intervene in viral infection and control viral epidemics. This review discusses current knowledge, prospective applications, opportunities, and challenges in the development of broad-spectrum antiviral agents.

  14. Increases in body mass index following initiation of methadone treatment.

    Science.gov (United States)

    Fenn, Jennifer M; Laurent, Jennifer S; Sigmon, Stacey C

    2015-04-01

    Despite the clear efficacy of methadone for opioid dependence, one less desirable phenomenon associated with methadone may be weight gain. We examined changes in body mass index (BMI) among patients entering methadone treatment. A retrospective chart review was conducted for 96 patients enrolled in an outpatient methadone clinic for ≥ 6 months. The primary outcome of BMI was assessed at intake and a subsequent physical examination approximately 1.8 ± 0.95 years later. Demographic, drug use and treatment characteristics were also examined. There was a significant increase in BMI following intake (pmethadone treatment enrollment was associated with clinically significant weight gain, particularly among female patients. This study highlights the importance of efforts to help patients mitigate weight gain during treatment, particularly considering the significant health and economic consequences of obesity for individuals and society more generally.

  15. HIV/HCV Antiviral Drug Interactions in the Era of Direct-acting Antivirals

    Science.gov (United States)

    Rice, Donald P.; Faragon, John J.; Banks, Sarah; Chirch, Lisa M.

    2016-01-01

    Abstract Therapy for human immunodeficiency virus (HIV) and chronic hepatitis C has evolved over the past decade, resulting in better control of infection and clinical outcomes; however, drug-drug interactions remain a significant hazard. Joint recommendations from the American Association for the Study of Liver Diseases and the Infectious Diseases Society of America regarding drug-drug interactions between HIV antiretroviral agents and direct-acting antiviral agents for treatment of hepatitis C virus (HCV) infection are reviewed here. This review is oriented to facilitate appropriate selection of an antiviral therapy regimen for HCV infection based on the choice of antiretroviral therapy being administered and, if necessary, switching antiretroviral regimens. PMID:27777891

  16. Related factor analysis of 48 dead patients with AIDS anti-viral treatment%艾滋病抗病毒治疗48例死亡患者相关因素分析

    Institute of Scientific and Technical Information of China (English)

    韦秋玲; 韦克召; 韦超; 潘利永; 韦幕葵

    2011-01-01

    Objective To analyze the related factors of the death in patients undergoing AIDS anti-viral treatment in our hospital. Methods The data were collected by the DataFax antiviral therapy information system which was used to analyze related conditions of dead patients with anti-viral treatment in our hospital. Results In the total of 315 AIDS patients accepted treatment from April of 2008 to June of 2010, in which 48 patients died. Of all the patients showed AIDS clinical Ⅲ stage or V stage symptoms before treatment. Among them the CD4 cell minimum value was 4 cell/μl, the maximum value was 263 cell/μl with the average of 36.4 cell/μl. The minimum treatment time was 1 d, the maximum time was 2 years and a half, of which 38 patients were treated for less than 3 months. 42 patients died due to AIDS-related diseases, including 9 patients who died of unsuccessful treatment. 11 cases died of opportunistic infections and gave up treatment during the treatment at home.22 patients died of AIDS-related diseases in 0.5 month to 8 months after stopping the treatment. Four eases died by suicide,and two cases with an unknown cause of death. Conclusion The main cause of death in our patients undergoing AIDS antiviral treatment was AIDS related disease, others include treatment discontinuation, economic hardship, discrimination and drug side effects.%目的 分析本院艾滋病抗病毒治疗死亡患者的相关因素.方法 利用国家统一使用的DataFax抗病毒治疗信息系统所收集的数据资料,对抗病毒治疗死亡患者的相关情况进行分析.结果 共有315例艾滋病患者接受治疗,有48例抗病毒治疗患者死亡.治疗前所有患者出现艾滋病临床Ⅲ期或Ⅳ期表现,CD4细胞最小值为4个/μl,最大值为263个/μl,平均为36.4个/μl.接受治疗时间最短1 d,最长2年半,其中39例的治疗时间小于3个月.死于艾滋病相关性疾病42例,其中9例系统治疗无效死亡,11例治疗过程中出现机会性感

  17. Diabetes Care and Treatment Project: A Joslin Telemedicine Initiative

    Science.gov (United States)

    2005-10-01

    in the development of microvascular complications of diabetic retinopathy and nephropathy or mitigation of the progression of these complications, d...follow-up eye care based on findings of their baseline examination. Those patients whose initial diagnosis suggests no significant diabetic retinopathy...Determine the level of agreement in retinopathy diagnosis comparing retinal images taken using the new JVN portable retinal imager and the clinical gold

  18. Is fixed combination therapy appropriate for initial hypertension treatment?

    Science.gov (United States)

    Elliott, William J

    2002-08-01

    Recent clinical trials in hypertension prove how seldom single drug therapy achieves target blood pressure (BP) and reduces cardiovascular morbidity and mortality. A natural response is the testing and marketing of fixed-dose combination products for hypertension, of which 14 have been approved in the United States since 1993. Currently, only five products are indicated by the Food and Drug Administration for initial therapy of hypertension; all include a diuretic. To achieve such an indication, studies must show not only safety and efficacy of the combination, but also BP lowering that is at least additive compared with the two agents given separately, as well as a "synergy" not present when each agent is given alone. Some advantages to initial combination therapy include greater BP reduction, improved adherence to pill taking, fewer side effects, and lower cost. The most likely candidates for initial combination therapy are patients with initial BP higher than 160/100 mm Hg, or those with a BP goal lower than the customary 140/90 mm Hg. These include patients with target organ damage, clinical cardiovascular disease, proteinuria, renal impairment, or diabetes mellitus. In many of these circumstances, an angiotensin converting enzyme inhibitor or angiotensin II receptor antagonist is frequently recommended; adding a diuretic or calcium antagonist to it is much more likely to result in achievement of the BP goal. More research is being done to explore the combination of not only two representatives from classes of conventional agents, but also other drugs that may help address the multiple manifestations of the "metabolic syndrome" that often accompanies hypertension.

  19. Arthrocentesis as initial treatment for temporomandibular joint arthropathy : A randomized controlled trial

    NARCIS (Netherlands)

    Vos, L. M.; Huddleston Slater, J. J. R.; Stegenga, B.

    2014-01-01

    Objective: To determine the effectiveness of arthrocentesis compared to conservative treatment as initial treatment with regard to temporomandibular joint pain and mandibular movement. Patients and methods: In this randomized controlled trial, 80 patients with arthralgia of the TMJ (classified accor

  20. [Triage and initial treatment of house fire victims].

    Science.gov (United States)

    Gremion, C; Wicky, R; Niquille, M

    2005-08-10

    Medical teams are often confronted to the numerous victims due to house fires. The time course of these disasters is difficult to predict and requires an excellent rescue organization as well as good cooperation with the fire brigades and appropriate matching and raising of means to the magnitude of the disaster. Victims usually present with three types of injuries: thermal, traumatic and toxic. In order to avoid an overflow of patients in surrounding hospitals, adequate triage and treatment are required on the field. Triage is best relized by history and physical examination and the main treatment remains maximal oxygen therapy. In case of severe monoxide intoxication, cyanide poisoning should be highly suspected.

  1. Exploiting Genetic Interference for Antiviral Therapy.

    Science.gov (United States)

    Tanner, Elizabeth J; Kirkegaard, Karla A; Weinberger, Leor S

    2016-05-01

    Rapidly evolving viruses are a major threat to human health. Such viruses are often highly pathogenic (e.g., influenza virus, HIV, Ebola virus) and routinely circumvent therapeutic intervention through mutational escape. Error-prone genome replication generates heterogeneous viral populations that rapidly adapt to new selection pressures, leading to resistance that emerges with treatment. However, population heterogeneity bears a cost: when multiple viral variants replicate within a cell, they can potentially interfere with each other, lowering viral fitness. This genetic interference can be exploited for antiviral strategies, either by taking advantage of a virus's inherent genetic diversity or through generating de novo interference by engineering a competing genome. Here, we discuss two such antiviral strategies, dominant drug targeting and therapeutic interfering particles. Both strategies harness the power of genetic interference to surmount two particularly vexing obstacles-the evolution of drug resistance and targeting therapy to high-risk populations-both of which impede treatment in resource-poor settings.

  2. Antiviral chemotherapy in veterinary medicine: current applications and perspectives.

    Science.gov (United States)

    Dal Pozzo, F; Thiry, E

    2014-12-01

    The current situation in the use of antiviral drugs in veterinary medicine is characterised by a novel and optimistic approach.Viruses of veterinary importance are still used as animal models in the developmentof human therapeutics, but there is growing interest in many of these viruses in the identification of antiviral molecules for use in both livestock and companion animals. The use of antiviral drugs in livestock animals is envisaged for the treatment or control of disease on a large scale (mass treatment), whereas in companion animals an individual approach is favoured. An overview of the most recent examples of research in the use of antivirals in veterinary medicine is presented, with particular emphasis on their in vivo applications.

  3. Antiviral Drug- and Multidrug Resistance in Cytomegalovirus Infected SCT Patients

    Directory of Open Access Journals (Sweden)

    Katharina Göhring

    2015-01-01

    Full Text Available In pediatric and adult patients after stem cell transplantation (SCT disseminated infections caused by human cytomegalovirus (HCMV can cause life threatening diseases. For treatment, the three antivirals ganciclovir (GCV, foscarnet (PFA and cidofovir (CDV are approved and most frequently used. Resistance to all of these antiviral drugs may induce a severe problem in this patient cohort. Responsible for resistance phenomena are mutations in the HCMV phosphotransferase-gene (UL97 and the polymerase-gene (UL54. Most frequently mutations in the UL97-gene are associated with resistance to GCV. Resistance against all three drugs is associated to mutations in the UL54-gene. Monitoring of drug resistance by genotyping is mostly done by PCR-based Sanger sequencing. For phenotyping with cell culture the isolation of HCMV is a prerequisite. The development of multidrug resistance with mutation in both genes is rare, but it is often associated with a fatal outcome. The manifestation of multidrug resistance is mostly associated with combined UL97/UL54-mutations. Normally, mutations in the UL97 gene occur initially followed by UL54 mutation after therapy switch. The appearance of UL54-mutation alone without any detection of UL97-mutation is rare. Interestingly, in a number of patients the UL97 mutation could be detected in specific compartments exclusively and not in blood.

  4. A Naval Postgraduate Dental School Analysis of Initial Endodontic Treatment

    Science.gov (United States)

    2013-06-01

    factors contributing to tooth extraction following non- surgical root canal treatment (NSRCT) at 2 years in a retrospective study examining nearly...YC, Hsiao CK, Chiang CP. Impact of diabetes mellitus, hypertension, and coronary artery disease on tooth extraction after nonsurgical endodontic

  5. In situ chitosan gelation initiated by atmospheric plasma treatment.

    Science.gov (United States)

    Molina, R; Jovancic, P; Vilchez, S; Tzanov, T; Solans, C

    2014-03-15

    This work reports on the feasibility of atmospheric dielectric barrier discharge (DBD) plasma as a novel synthetic pathway for the liquid phase gelation of chitosan. The DBD plasma chitosan gelation process did not significantly alter the chemical structure of the biopolymer as confirmed by FTIR study. However, the oxidation processes and local heating effect associated with the solvent evaporation during the plasma treatment could provoke both reaction of chitosan degradation and the cleavage of β-1-4-glycosidic linkages with the concomitant generation of aldehyde groups able to crosslink via Schiff-base with amino groups from other chitosan molecules. Shear viscosity measurements suggested the formation of chitosan fragments of lower molecular weight after the plasma treatment of 1% (w/v) chitosan and fragments of higher molecular weight after the plasma treatment of 2% (w/v) chitosan. The crosslinking density of hydrogels generated during the in situ DBD plasma chitosan gelation process increased as a function of the treatment time and concentration of chitosan. As of consequence of the increase of the cross-linking density, the equilibrium swelling ratio and water content decreased significantly.

  6. Genomic markers to tailor treatments: waiting or initiating?

    NARCIS (Netherlands)

    P. Tajik; P.M. Bossuyt

    2011-01-01

    The decade since the publication of the Human Genome Project draft has ended with the discovery of hundreds of genomic markers related to diseases and phenotypes. However, the project has not yet delivered on its promise to tailor treatments for individuals. The number of genomic markers in clinical

  7. Antiviral Strategies for Pandemic and Seasonal Influenza

    Directory of Open Access Journals (Sweden)

    Fang Fang

    2010-08-01

    Full Text Available While vaccines are the primary public health response to seasonal and pandemic flu, short of a universal vaccine there are inherent limitations to this approach. Antiviral drugs provide valuable alternative options for treatment and prophylaxis of influenza. Here, we will review drugs and drug candidates against influenza with an emphasis on the recent progress of a host-targeting entry-blocker drug candidate, DAS181, a sialidase fusion protein.

  8. Barriers to and Reasons for Treatment Initiation Among Gambling Help-line Callers.

    Science.gov (United States)

    Khayyat-Abuaita, Ula; Ostojic, Dragana; Wiedemann, Ashley; Arfken, Cynthia L; Ledgerwood, David M

    2015-08-01

    Identifying barriers to seeking treatment is essential for increasing problem gambler treatment initiation in the community, given that as few as 1 in 10 problem gamblers ever seek treatment. Further, many problem gamblers who take the initial step of contacting problem gambling help-lines do not subsequently go on to attend face-to-face treatment. There is limited research examining reasons for attending treatment among this population. This study addressed these gaps in the literature by examining barriers and attractions to treatment among callers to the State of Michigan Problem Gambling Help-line. In total, 143 callers (n = 86 women) completed the Barriers to Treatment for Problem Gambling (BTPG) questionnaire and responded to open-ended questions regarding barriers to and reasons for treatment initiation, as part of a telephone interview. Greater endorsement of barriers to treatment was associated with a lower likelihood of initiating treatment, especially perceived absence of problem and treatment unavailability. Correspondingly, problem gamblers who identified more reasons to attend treatment were more likely to attend, with positive treatment perceptions being the most influential. These findings can help get people into treatment by addressing barriers and fostering reasons for attending treatment, as well as reminding clinicians of the importance of identifying and addressing individual treatment barriers among patients with problem gambling.

  9. Treatment outcomes after initiation of exenatide twice daily or insulin in clinical practice

    DEFF Research Database (Denmark)

    Ostenson, Claes-Göran; Matthaei, Stephan; Reaney, Matthew;

    2013-01-01

    OBJECTIVE: The CHanges to treatment and Outcomes in patients with type 2 diabetes initiating InjeCtablE therapy (CHOICE) study assessed time to, and reasons for, significant treatment change after patients with type 2 diabetes (T2DM) initiated their first injectable glucose-lowering therapy (exen...

  10. Cost effectiveness of arthrocentesis as initial treatment for temporomandibular joint arthralgia: A randomized controlled trial

    NARCIS (Netherlands)

    Vos, L.M.; Stant, A.D.; Quik, E.H.; Huddleston Slater, J.J.R.; Stegenga, B.

    2013-01-01

    Objective: To determine the cost effectiveness of arthrocentesis as initial treatment compared to care as usual (CAU) for temporomandibular joint (TMJ) arthralgia. Materials and methods: 80 patients were randomly allocated to arthrocentesis as initial treatment (n = 40) or CAU (n = 40). Arthrocentes

  11. HIV Care and Treatment Beliefs among Patients Initiating Antiretroviral Treatment (ART) in Oromia, Ethiopia.

    Science.gov (United States)

    Tymejczyk, Olga; Hoffman, Susie; Kulkarni, Sarah Gorrell; Gadisa, Tsigereda; Lahuerta, Maria; Remien, Robert H; Elul, Batya; El-Sadr, Wafaa; Melaku, Zenebe; Nash, Denis

    2016-05-01

    To better understand patient beliefs, which may influence adherence to HIV care and treatment, we examined three dimensions of beliefs among Ethiopian adults (n = 1177) initiating antiretroviral therapy (ART). Beliefs about benefits of ART/HIV clinical care were largely accurate, but few patients believed in the ability of ART to prevent sexual transmission and many thought Holy Water could cure HIV. Factors associated with lower odds of accurate beliefs included advanced HIV, lack of formal education, and Muslim religion (benefits of ART/clinical care); secondary or university education and more clinic visits (ART to prevent sexual transmission); and pregnancy and Orthodox Christian religion (Holy Water). Assessment of patient beliefs may help providers identify areas needing reinforcement. In this setting, counselors also need to stress the benefits of ART as prevention and that Holy Water should not be used to the exclusion of HIV care and ART.

  12. Antiviral immunity in amphibians.

    Science.gov (United States)

    Chen, Guangchun; Robert, Jacques

    2011-11-01

    Although a variety of virus species can infect amphibians, diseases caused by ranaviruses ([RVs]; Iridoviridae) have become prominent, and are a major concern for biodiversity, agriculture and international trade. The relatively recent and rapid increase in prevalence of RV infections, the wide range of host species infected by RVs, the variability in host resistance among population of the same species and among different developmental stages, all suggest an important involvement of the amphibian immune system. Nevertheless, the roles of the immune system in the etiology of viral diseases in amphibians are still poorly investigated. We review here the current knowledge of antiviral immunity in amphibians, focusing on model species such as the frog Xenopus and the salamander (Ambystoma tigrinum), and on recent progress in generating tools to better understand how host immune defenses control RV infections, pathogenicity, and transmission.

  13. Dasatinib and Doxorubicin Treatment of Sarcoma Initiating Cells

    DEFF Research Database (Denmark)

    Aggerholm-Pedersen, Ninna; Demuth, Christina; Safwat, Akmal;

    2016-01-01

    growth factor receptor (EGFR) was activated in both cell lines. However hMSC-TERT20-CE8 exhibited significantly higher expression of the EGFR ligands. EGFR inhibitors such as erlotinib and afatinib alone or in combination with doxorubicin failed to further decrease cell viability of hMSC-TERT20-CE8......) stem cell line hMSC-TERT4 and a transformed cell line hMSC-TERT20-CE8, known to form sarcoma-like tumours when implanted in immune-deficient mice, were used as models. Receptor tyrosine kinase (RTK) activation was analysed by RTK arrays and cellular viability after tyrosine kinases inhibitor (TKI....... However, inhibition with the TKI dasatinib in combination with doxorubicin decreased cell viability of the hMSC-TERT20-CE8 cell line. Conclusion. Our results demonstrate that dasatinib, but not EGFR-directed treatment, can decrease cell viability of stromal cancer stem cells less sensitive to doxorubicin....

  14. Breast Cancer-Initiating Cells: Insights into Novel Treatment Strategies

    Directory of Open Access Journals (Sweden)

    Maria Grazia Daidone

    2011-03-01

    Full Text Available There is accumulating evidence that breast cancer may arise from mutated mammary stem/progenitor cells which have been termed breast cancer-initiating cells (BCIC. BCIC identified in clinical specimens based on membrane phenotype (CD44+/CD24−/low and/or CD133+ expression or enzymatic activity of aldehyde dehydrogenase 1 (ALDH1+, have been demonstrated to have stem/progenitor cell properties, and are tumorigenic when injected in immunocompromized mice at very low concentrations. BCIC have also been isolated and in vitro propagated as non-adherent spheres of undifferentiated cells, and stem cell patterns have been recognized even in cancer cell lines. Recent findings indicate that aberrant regulation of self renewal is central to cancer stem cell biology. Alterations in genes involved in self-renewal pathways, such as Wnt, Notch, sonic hedgehog, PTEN and BMI, proved to play a role in breast cancer progression. Hence, targeting key elements mediating the self renewal of BCIC represents an attractive option, with a solid rationale, clearly identifiable molecular targets, and adequate knowledge of the involved pathways. Possible concerns are related to the poor knowledge of tolerance and efficacy of inhibiting self-renewal mechanisms, because the latter are key pathways for a variety of biological functions and it is unknown whether their interference would kill BCIC or simply temporarily stop them. Thus, efforts to develop BCIC-targeted therapies should not only be focused on interfering on self-renewal, but could seek to identify additional molecular targets, like those involved in regulating EMT-related pathways, in reversing the MDR phenotype, in inducing differentiation and controlling cell survival pathways.

  15. Breast Cancer-Initiating Cells: Insights into Novel Treatment Strategies

    Energy Technology Data Exchange (ETDEWEB)

    Santilli, Guido; Binda, Mara; Zaffaroni, Nadia; Daidone, Maria Grazia, E-mail: mariagrazia.daidone@istitutotumori.mi.it [Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS-Istituto Nazionale dei Tumori, Via Amadeo 42, Milan 20133 (Italy)

    2011-03-16

    There is accumulating evidence that breast cancer may arise from mutated mammary stem/progenitor cells which have been termed breast cancer-initiating cells (BCIC). BCIC identified in clinical specimens based on membrane phenotype (CD44{sup +}/CD24{sup −/low} and/or CD133{sup +} expression) or enzymatic activity of aldehyde dehydrogenase 1 (ALDH1{sup +}), have been demonstrated to have stem/progenitor cell properties, and are tumorigenic when injected in immunocompromized mice at very low concentrations. BCIC have also been isolated and in vitro propagated as non-adherent spheres of undifferentiated cells, and stem cell patterns have been recognized even in cancer cell lines. Recent findings indicate that aberrant regulation of self renewal is central to cancer stem cell biology. Alterations in genes involved in self-renewal pathways, such as Wnt, Notch, sonic hedgehog, PTEN and BMI, proved to play a role in breast cancer progression. Hence, targeting key elements mediating the self renewal of BCIC represents an attractive option, with a solid rationale, clearly identifiable molecular targets, and adequate knowledge of the involved pathways. Possible concerns are related to the poor knowledge of tolerance and efficacy of inhibiting self-renewal mechanisms, because the latter are key pathways for a variety of biological functions and it is unknown whether their interference would kill BCIC or simply temporarily stop them. Thus, efforts to develop BCIC-targeted therapies should not only be focused on interfering on self-renewal, but could seek to identify additional molecular targets, like those involved in regulating EMT-related pathways, in reversing the MDR phenotype, in inducing differentiation and controlling cell survival pathways.

  16. Clinical Implications of Antiviral Resistance in Influenza

    Directory of Open Access Journals (Sweden)

    Timothy C. M. Li

    2015-09-01

    Full Text Available Influenza is a major cause of severe respiratory infections leading to excessive hospitalizations and deaths globally; annual epidemics, pandemics, and sporadic/endemic avian virus infections occur as a result of rapid, continuous evolution of influenza viruses. Emergence of antiviral resistance is of great clinical and public health concern. Currently available antiviral treatments include four neuraminidase inhibitors (oseltamivir, zanamivir, peramivir, laninamivir, M2-inibitors (amantadine, rimantadine, and a polymerase inhibitor (favipiravir. In this review, we focus on resistance issues related to the use of neuraminidase inhibitors (NAIs. Data on primary resistance, as well as secondary resistance related to NAI exposure will be presented. Their clinical implications, detection, and novel therapeutic options undergoing clinical trials are discussed.

  17. Clinical Implications of Antiviral Resistance in Influenza.

    Science.gov (United States)

    Li, Timothy C M; Chan, Martin C W; Lee, Nelson

    2015-09-14

    Influenza is a major cause of severe respiratory infections leading to excessive hospitalizations and deaths globally; annual epidemics, pandemics, and sporadic/endemic avian virus infections occur as a result of rapid, continuous evolution of influenza viruses. Emergence of antiviral resistance is of great clinical and public health concern. Currently available antiviral treatments include four neuraminidase inhibitors (oseltamivir, zanamivir, peramivir, laninamivir), M2-inibitors (amantadine, rimantadine), and a polymerase inhibitor (favipiravir). In this review, we focus on resistance issues related to the use of neuraminidase inhibitors (NAIs). Data on primary resistance, as well as secondary resistance related to NAI exposure will be presented. Their clinical implications, detection, and novel therapeutic options undergoing clinical trials are discussed.

  18. 78 FR 62506 - TRICARE; Coverage of Care Related to Non-Covered Initial Surgery or Treatment

    Science.gov (United States)

    2013-10-22

    ... a non-covered incident of treatment (such as nonadjunctive dental care or cosmetic surgery) but only... Initial Surgery or Treatment AGENCY: Office of the Secretary, Department of Defense. ACTION: Proposed rule... on a determination that a waiver authorizing the original non-covered surgery or treatment...

  19. Comparative study of infantile diarrhea Ning combined with antiviral drug and single use of antiviral drugs in the treatment of diarrhea in children%小儿腹泻宁联合抗病毒药物与单用抗病毒药物治疗小儿腹泻的对比研究

    Institute of Scientific and Technical Information of China (English)

    舒航

    2015-01-01

    Objective To explore the comparative study of infantile diarrhea Ning combined with antiviral drug and single use of antiviral drugs in the treatment of diarrhea in children.Methods 100 cases of infantile diarrhea in children from 2013 May -2014 year in June to pediatric clinic of our hospital, all patients were randomly divided into observation group and control group with 50 cases in each group. The clinical efficacy of the two groups of children with stool, recovery time, vomiting, time and the temperature recovery time and adverse reaction were compared.ResultsThe clinical total effective rate of observation group was 94.00%, significantly higher than the control group 82.00%, two groups, the difference was statistically significant (P<0.05). Stool observation group with recovery time, vomiting, time and the temperature recovery time was significantly lower than the control group, the two groups, the difference was statistically significant (P<0.05). Two groups of children with severe adverse reaction hadn. occurred.Conclusion Diarrhea in children with infantile diarrhea Ning combined with antiviral drug treatment, can significantly improve the clinical efficacy, shorten the recovery time of clinical symptoms.%目的 探讨小儿腹泻宁联合抗病毒药物治疗小儿腹泻与单用抗病毒药物治疗的不同疗效.方法 选取2013年5月~2014年6月来我院儿科就诊的小儿腹泻患儿100例,所有患儿随机分为观察组及对照组各50例.对两组患儿的临床疗效,大便性状恢复时间,呕吐时间及体温恢复时间及不良反应情况进行比较.结果 观察组的临床总有效率为94.00%,明显高于对照组的82.00%,两组比较,差异有统计学意义(P<0.05).观察组患儿的大便性状恢复,体温恢复及呕吐的时间显著低于对照组,两组比较,差异有统计学意义(P<0.05).两组患儿治疗期间皆无严重不良反应发生.结论 小儿腹泻宁联合抗病毒药物治疗小儿腹泻临床疗效

  20. Antiviral Drug Research Proposal Activity

    Directory of Open Access Journals (Sweden)

    Lisa Injaian

    2011-03-01

    Full Text Available The development of antiviral drugs provides an excellent example of how basic and clinical research must be used together in order to achieve the final goal of treating disease. A Research Oriented Learning Activity was designed to help students to better understand how basic and clinical research can be combined toward a common goal. Through this project students gained a better understanding of the process of scientific research and increased their information literacy in the field of virology. The students worked as teams to research the many aspects involved in the antiviral drug design process, with each student becoming an "expert" in one aspect of the project. The Antiviral Drug Research Proposal (ADRP culminated with students presenting their proposals to their peers and local virologists in a poster session. Assessment data showed increased student awareness and knowledge of the research process and the steps involved in the development of antiviral drugs as a result of this activity.

  1. Antiviral lead compounds from marine sponges

    KAUST Repository

    Sagar, Sunil

    2010-10-11

    Marine sponges are currently one of the richest sources of pharmacologically active compounds found in the marine environment. These bioactive molecules are often secondary metabolites, whose main function is to enable and/or modulate cellular communication and defense. They are usually produced by functional enzyme clusters in sponges and/or their associated symbiotic microorganisms. Natural product lead compounds from sponges have often been found to be promising pharmaceutical agents. Several of them have successfully been approved as antiviral agents for clinical use or have been advanced to the late stages of clinical trials. Most of these drugs are used for the treatment of human immunodeficiency virus (HIV) and herpes simplex virus (HSV). The most important antiviral lead of marine origin reported thus far is nucleoside Ara-A (vidarabine) isolated from sponge Tethya crypta. It inhibits viral DNA polymerase and DNA synthesis of herpes, vaccinica and varicella zoster viruses. However due to the discovery of new types of viruses and emergence of drug resistant strains, it is necessary to develop new antiviral lead compounds continuously. Several sponge derived antiviral lead compounds which are hopedto be developed as future drugs are discussed in this review. Supply problems are usually the major bottleneck to the development of these compounds as drugs during clinical trials. However advances in the field of metagenomics and high throughput microbial cultivation has raised the possibility that these techniques could lead to the cost-effective large scale production of such compounds. Perspectives on biotechnological methods with respect to marine drug development are also discussed. 2010 by the authors; licensee MDPI.

  2. Perspective of Use of Antiviral Peptides against Influenza Virus

    Directory of Open Access Journals (Sweden)

    Sylvie Skalickova

    2015-10-01

    Full Text Available The threat of a worldwide influenza pandemic has greatly increased over the past decade with the emergence of highly virulent avian influenza strains. The increased frequency of drug-resistant influenza strains against currently available antiviral drugs requires urgent development of new strategies for antiviral therapy, too. The research in the field of therapeutic peptides began to develop extensively in the second half of the 20th century. Since then, the mechanisms of action for several peptides and their antiviral prospect received large attention due to the global threat posed by viruses. Here, we discussed the therapeutic properties of peptides used in influenza treatment. Peptides with antiviral activity against influenza can be divided into three main groups. First, entry blocker peptides such as a Flupep that interact with influenza hemagglutinin, block its binding to host cells and prevent viral fusion. Second, several peptides display virucidal activity, disrupting viral envelopes, e.g., Melittin. Finally, a third set of peptides interacts with the viral polymerase complex and act as viral replication inhibitors such as PB1 derived peptides. Here, we present a review of the current literature describing the antiviral activity, mechanism and future therapeutic potential of these influenza antiviral peptides.

  3. Diagnosis and antiviral intervention strategies for mitigating an influenza epidemic.

    Directory of Open Access Journals (Sweden)

    Robert Moss

    Full Text Available BACKGROUND: Many countries have amassed antiviral stockpiles for pandemic preparedness. Despite extensive trial data and modelling studies, it remains unclear how to make optimal use of antiviral stockpiles within the constraints of healthcare infrastructure. Modelling studies informed recommendations for liberal antiviral distribution in the pandemic phase, primarily to prevent infection, but failed to account for logistical constraints clearly evident during the 2009 H1N1 outbreaks. Here we identify optimal delivery strategies for antiviral interventions accounting for logistical constraints, and so determine how to improve a strategy's impact. METHODS AND FINDINGS: We extend an existing SEIR model to incorporate finite diagnostic and antiviral distribution capacities. We evaluate the impact of using different diagnostic strategies to decide to whom antivirals are delivered. We then determine what additional capacity is required to achieve optimal impact. We identify the importance of sensitive and specific case ascertainment in the early phase of a pandemic response, when the proportion of false-positive presentations may be high. Once a substantial percentage of ILI presentations are caused by the pandemic strain, identification of cases for treatment on syndromic grounds alone results in a greater potential impact than a laboratory-dependent strategy. Our findings reinforce the need for a decentralised system capable of providing timely prophylaxis. CONCLUSIONS: We address specific real-world issues that must be considered in order to improve pandemic preparedness policy in a practical and methodologically sound way. Provision of antivirals on the scale proposed for an effective response is infeasible using traditional public health outbreak management and contact tracing approaches. The results indicate to change the transmission dynamics of an influenza epidemic with an antiviral intervention, a decentralised system is required for

  4. Association of gastrointestinal events and osteoporosis treatment initiation in newly diagnosed osteoporotic Israeli women

    OpenAIRE

    J. Yu; Goldshtein, I.; Shalev, V.; Chodick, G.; Ish‐Shalom, S.; Sharon, O.; A. Modi

    2015-01-01

    Summary Background The objective was to examine the association of gastrointestinal (GI) events and osteoporosis treatment initiation patterns among postmenopausal women following an osteoporosis diagnosis from an Israeli health plan. Methods This retrospective analysis of claims records included women aged ≥ 55 years with ≥ 1 osteoporosis diagnosis (date of first diagnosis was index date). Osteoporosis treatment initiation was defined as use of osteoporosis therapy (oral bisphosphonates or o...

  5. Antiviral drugs for viruses other than human immunodeficiency virus.

    Science.gov (United States)

    Razonable, Raymund R

    2011-10-01

    Most viral diseases, with the exception of those caused by human immunodeficiency virus, are self-limited illnesses that do not require specific antiviral therapy. The currently available antiviral drugs target 3 main groups of viruses: herpes, hepatitis, and influenza viruses. With the exception of the antisense molecule fomivirsen, all antiherpes drugs inhibit viral replication by serving as competitive substrates for viral DNA polymerase. Drugs for the treatment of influenza inhibit the ion channel M(2) protein or the enzyme neuraminidase. Combination therapy with Interferon-α and ribavirin remains the backbone treatment for chronic hepatitis C; the addition of serine protease inhibitors improves the treatment outcome of patients infected with hepatitis C virus genotype 1. Chronic hepatitis B can be treated with interferon or a combination of nucleos(t)ide analogues. Notably, almost all the nucleos(t) ide analogues for the treatment of chronic hepatitis B possess anti-human immunodeficiency virus properties, and they inhibit replication of hepatitis B virus by serving as competitive substrates for its DNA polymerase. Some antiviral drugs possess multiple potential clinical applications, such as ribavirin for the treatment of chronic hepatitis C and respiratory syncytial virus and cidofovir for the treatment of cytomegalovirus and other DNA viruses. Drug resistance is an emerging threat to the clinical utility of antiviral drugs. The major mechanisms for drug resistance are mutations in the viral DNA polymerase gene or in genes that encode for the viral kinases required for the activation of certain drugs such as acyclovir and ganciclovir. Widespread antiviral resistance has limited the clinical utility of M(2) inhibitors for the prevention and treatment of influenza infections. This article provides an overview of clinically available antiviral drugs for the primary care physician, with a special focus on pharmacology, clinical uses, and adverse effects.

  6. Sleep Hygiene and Melatonin Treatment for Children and Adolescents with ADHD and Initial Insomnia

    Science.gov (United States)

    Weiss, Margaret D.; Wasdell, Michael B.; Bomben, Melissa M.; Rea, Kathleen J.; Freeman, Roger D.

    2006-01-01

    Objective: To evaluate the efficacy of sleep hygiene and melatonin treatment for initial insomnia in children with attention-deficit/hyperactivity disorder (ADHD). Method: Twenty-seven stimulant-treated children (6-14 years of age) with ADHD and initial insomnia (greater than 60 minutes) received sleep hygiene intervention. Nonresponders were…

  7. Improving Question-Asking Initiations in Young Children with Autism Using Pivotal Response Treatment

    Science.gov (United States)

    Koegel, Robert L.; Bradshaw, Jessica L.; Ashbaugh, Kristen; Koegel, Lynn Kern

    2014-01-01

    Social initiations make up a core deficit for children with autism spectrum disorder (ASD). In particular, initiated questions during social interactions are often minimal or absent in this population. In the context of a multiple baseline design, the efficacy of using the motivational procedures of Pivotal Response Treatment to increase social…

  8. Imaging analysis of nuclear antiviral factors through direct detection of incoming adenovirus genome complexes.

    Science.gov (United States)

    Komatsu, Tetsuro; Will, Hans; Nagata, Kyosuke; Wodrich, Harald

    2016-04-22

    Recent studies involving several viral systems have highlighted the importance of cellular intrinsic defense mechanisms through nuclear antiviral proteins that restrict viral propagation. These factors include among others components of PML nuclear bodies, the nuclear DNA sensor IFI16, and a potential restriction factor PHF13/SPOC1. For several nuclear replicating DNA viruses, it was shown that these factors sense and target viral genomes immediately upon nuclear import. In contrast to the anticipated view, we recently found that incoming adenoviral genomes are not targeted by PML nuclear bodies. Here we further explored cellular responses against adenoviral infection by focusing on specific conditions as well as additional nuclear antiviral factors. In line with our previous findings, we show that neither interferon treatment nor the use of specific isoforms of PML nuclear body components results in co-localization between incoming adenoviral genomes and the subnuclear domains. Furthermore, our imaging analyses indicated that neither IFI16 nor PHF13/SPOC1 are likely to target incoming adenoviral genomes. Thus our findings suggest that incoming adenoviral genomes may be able to escape from a large repertoire of nuclear antiviral mechanisms, providing a rationale for the efficient initiation of lytic replication cycle.

  9. 早期足量抗病毒治疗带状疱疹临床疗效观察%Clinical observation on treatment of herpes zoster with high-dose antiviral therapy at early stage

    Institute of Scientific and Technical Information of China (English)

    彭光玲; 李惠

    2013-01-01

    目的:对比在治疗带状疱疹时早期足量使用阿昔洛韦类抗病毒药物与常规剂量治疗的病例在临床上的疗效.方法:以我科从2011年6月至2012年2月收治的带状疱疹患者为研究来源.以患者自愿为原则,对比分析观察组患者与对照组患者治疗结束后的临床疗效与带状疱疹后遗神经痛(postherpetic neuragia,PHN)的发生率.结果:对比观察治疗带状疱疹在疼痛缓解时间、止庖时间、皮损开始结痂时间、50%皮损结痂时间、皮损消失时间等各方面上,观察组明显短于两组对照组,差异具有统计学意义(P<0.05),但带状疱疹PHN的发生率及疼痛程度治疗后1、2、3、6月观察组与对照组其结果并无差异.对照组A与对照组B因无可比性,故未做对比.结论:对带状疱疹治疗,早期足量使用抗病毒药物其治疗效果显著,应当在临床上提倡,但对于是否可以减少带状疱疹PHN的发生及减缓其疼痛程度需要更进一步的临床研究.%Objective:To compare the clinical effect of herpes zoster(HZ) treated by routine dose and high-dose valacyclovir(VCV) classical antiviral drugs. Methods: Research source comes from the patients with herpes zoster admitted to our department from June 2011 to February 2012. Based on the principle of voluntary, patients with onset time 5 d were treated by high-dose antiviral therapy(control group B). Clinical effects and incidences of postherpetic neuralgia (PHN) of herpes zoster in the three groups at the end of treatment were compared and analyzed. Results:Pain relieving time,cessation time of new lesion,beginning time of skin lesion crusting,50% lesion crusting time and subsiding time of skin lesions were significantly shorter in observation group than in control groups (A and B) during the treatment of herpes zoster, with statistical significances (P<0.05). There was no significant difference in incidences and pain degrees of PHN of herpes zoster within the first

  10. Сost-effectiveness of the second wave of protease inhibitors in the treatment of chronic hepatitis C (genotype 1 in patients not previously treated with antiviral drugs, and for relapsed disease

    Directory of Open Access Journals (Sweden)

    A. V. Rudakova

    2016-01-01

    Full Text Available The protease inhibitors (PI actively using for the treatment of chronic hepatitis C (CHC.The aim of this analysis was to evaluate the cost-effectiveness of narlaprevir and simeprevir in the CHC (genotype 1 therapy in treatment-naïve patients and relapses.Material and methods. Analysis of the cost-effectiveness of simeprevir and narlaprevir was conducted from the perspective of the health care system and base on QUEST-1, QUEST-2, ASPIRE and PIONEER clinical trials. The relative risk of achieving SVR 24 compared to the peg-INF + RBV therapy was used in the model. Treatment discontinuation in patients receiving narlaprevir assumed in the absence of a SVR after 12 weeks and in patients receiving simeprevir in the SVR absence after 4 weeks. The cost of narlaprevir was calculate based on estimated registration price in case of EDL (essential pharmaceutical list approved by MOH inclusion, including VAT (10% and 10% as trade margin. Costs of other antiviral products were in line with the results of 2015 average auctions prices.Results. In the base case costs on antiviral products with narlaprevir as first-line therapy are lower compared with simeprevir by 12,2% (950,6 and 1083,0 thousand RUR, respectively, and the cost per patient with SVR 24 by 7,8%. In patients group after relapse costs on antiviral products with narlaprevir as first-line therapy will decrease compared with simeprevir by 4,3% (971,3 and 1014,7 thousand RUR, respectively, and the cost per patient with SVR 24 by 25,0%. The sensitivity analysis demonstrated a high reliability of obtained results. Thus, assuming equal clinical effectiveness of narlaprevir and simeprevir, costs of treatment naive patients will be 10.6% lower for narlaprevir group compared to simeprevir group (953,0 and 1066,0 thousand rur, respectively, and by 12,9% for the treatment of relapses (957,9 and 1100,0 thousand RUR, respectively.Conclusions. With comparable clinical efficacy and

  11. Prior criminal charges and outcomes among individuals initiating office-based buprenorphine treatment

    OpenAIRE

    Harris, Elizabeth E; Jacapraro, Janet S; Rastegar, Darius A

    2013-01-01

    Background There is little data on the impact of prior criminal activity on the treatment of opioid dependence with office-based buprenorphine. The goal of this study was to investigate the association between prior criminal charges and treatment outcomes in a cohort of patients initiating buprenorphine treatment in a primary care practice. Methods This was a retrospective study of 252 consecutive patients with opioid dependence who were given at least one prescription for buprenorphine in a ...

  12. Factors associated with delays in treatment initiation after tuberculosis diagnosis in two districts of India.

    Directory of Open Access Journals (Sweden)

    Durba Paul

    Full Text Available BACKGROUND: Excessive time between diagnosis and initiation of tuberculosis (TB treatment contributes to ongoing TB transmission and should be minimized. In India, Revised National TB Control Programme (RNTCP focuses on indicator start of treatment within 7 days of diagnosis for patients with sputum smear-positive PTB for monitoring DOTS implementation. OBJECTIVES: To determine length of time between diagnosis and initiation of treatment and factors associated with delays of more than 7 days in smear-positive pulmonary TB. METHODS: Using existing programme records such as the TB Register, treatment cards, and the laboratory register, we conducted a retrospective cohort study of all patients with smear-positive pulmonary TB registered from July-September 2010 in two districts in India. A random sample of patients with pulmonary TB who experienced treatment delay of more than 7 days was interviewed using structured questionnaire. RESULTS: 2027 of 3411 patients registered with pulmonary TB were smear-positive. 711(35% patients had >7 days between diagnosis and treatment and 262(13% had delays >15 days. Mean duration between TB diagnosis and treatment initiation was 8 days (range = 0-128 days. Odds of treatment delay >7 days was 1.8 times more likely among those who had been previously treated (95% confidence interval [CI] 1.5-2.3 and 1.6 (95% CI 1.3-1.8 times more likely among those diagnosed in health facilities without microscopy centers. The main factors associated with a delay >7 days were: patient reluctance to start a re-treatment regimen, patients seeking second opinions, delay in transportation of drugs to the DOT centers and delay in initial home visits. To conclude, treatment delay >7 days was associated with a number of factors that included history of previous treatment and absence of TB diagnostic services in the local health facility. Decentralized diagnostic facilities and improved referral procedures may reduce such treatment

  13. Criminal charges prior to and after initiation of office-based buprenorphine treatment

    Directory of Open Access Journals (Sweden)

    Harris Elizabeth E

    2012-03-01

    Full Text Available Abstract Background There is little data on the impact of office-based buprenorphine therapy on criminal activity. The goal of this study was to determine the impact of primary care clinic-based buprenorphine maintenance therapy on rates of criminal charges and the factors associated with criminal charges in the 2 years after initiation of treatment. Methods We collected demographic and outcome data on 252 patients who were given at least one prescription for buprenorphine. We searched a public database of criminal charges and recorded criminal charges prior to and after enrollment. We compared the total number of criminal cases and drug cases 2 years before versus 2 years after initiation of treatment. Results There was at least one criminal charge made against 38% of the subjects in the 2 years after initiation of treatment; these subjects were more likely to have used heroin, to have injected drugs, to have had any prior criminal charges, and recent criminal charges. There was no significant difference in the number of subjects with any criminal charge or a drug charge before and after initiation of treatment. Likewise, the mean number of all cases and drug cases was not significantly different between the two periods. However, among those who were opioid-negative for 6 or more months in the first year of treatment, there was a significant decline in criminal cases. On multivariable analysis, having recent criminal charges was significantly associated with criminal charges after initiation of treatment (adjusted odds ratio 3.92; subjects who were on opioid maintenance treatment prior to enrollment were significantly less likely to have subsequent criminal charges (adjusted odds ratio 0.52. Conclusions Among subjects with prior criminal charges, initiation of office-based buprenorphine treatment did not appear to have a significant impact on subsequent criminal charges.

  14. Progress in the development of poliovirus antiviral agents and their essential role in reducing risks that threaten eradication.

    Science.gov (United States)

    McKinlay, Mark A; Collett, Marc S; Hincks, Jeffrey R; Oberste, M Steven; Pallansch, Mark A; Okayasu, Hiromasa; Sutter, Roland W; Modlin, John F; Dowdle, Walter R

    2014-11-01

    Chronic prolonged excretion of vaccine-derived polioviruses by immunodeficient persons (iVDPV) presents a personal risk of poliomyelitis to the patient as well as a programmatic risk of delayed global eradication. Poliovirus antiviral drugs offer the only mitigation of these risks. Antiviral agents may also have a potential role in the management of accidental exposures and in certain outbreak scenarios. Efforts to discover and develop poliovirus antiviral agents have been ongoing in earnest since the formation in 2007 of the Poliovirus Antivirals Initiative. The most advanced antiviral, pocapavir (V-073), is a capsid inhibitor that has recently demonstrated activity in an oral poliovirus vaccine human challenge model. Additional antiviral candidates with differing mechanisms of action continue to be profiled and evaluated preclinically with the goal of having 2 antivirals available for use in combination to treat iVDPV excreters.

  15. Operational challenges in diagnosing multi-drug resistant TB and initiating treatment in Andhra Pradesh, India.

    Directory of Open Access Journals (Sweden)

    Sarabjit S Chadha

    Full Text Available BACKGROUND: Revised National TB Control Programme (RNTCP, Andhra Pradesh, India. There is limited information on whether MDR-TB suspects are identified, undergo diagnostic assessment and are initiated on treatment according to the programme guidelines. OBJECTIVES: To assess i using the programme definition, the number and proportion of MDR-TB suspects in a large cohort of TB patients on first-line treatment under RNTCP ii the proportion of these MDR-TB suspects who underwent diagnosis for MDR-TB and iii the number and proportion of those diagnosed as MDR-TB who were successfully initiated on treatment. METHODS: A retrospective cohort analysis, by reviewing RNTCP records and reports, was conducted in four districts of Andhra Pradesh, India, among patients registered for first line treatment during October 2008 to December 2009. RESULTS: Among 23,999 TB patients registered for treatment there were 559 (2% MDR-TB suspects (according to programme definition of which 307 (55% underwent diagnosis and amongst these 169 (55% were found to be MDR-TB. Of the MDR-TB patients, 112 (66% were successfully initiated on treatment. Amongst those eligible for MDR-TB services, significant proportions are lost during the diagnostic and treatment initiation pathway due to a variety of operational challenges. The programme needs to urgently address these challenges for effective delivery and utilisation of the MDR-TB services.

  16. Viral Ancestors of Antiviral Systems

    Directory of Open Access Journals (Sweden)

    Luis P. Villarreal

    2011-10-01

    Full Text Available All life must survive their corresponding viruses. Thus antiviral systems are essential in all living organisms. Remnants of virus derived information are also found in all life forms but have historically been considered mostly as junk DNA. However, such virus derived information can strongly affect host susceptibility to viruses. In this review, I evaluate the role viruses have had in the origin and evolution of host antiviral systems. From Archaea through bacteria and from simple to complex eukaryotes I trace the viral components that became essential elements of antiviral immunity. I conclude with a reexamination of the ‘Big Bang’ theory for the emergence of the adaptive immune system in vertebrates by horizontal transfer and note how viruses could have and did provide crucial and coordinated features.

  17. Viral ancestors of antiviral systems.

    Science.gov (United States)

    Villarreal, Luis P

    2011-10-01

    All life must survive their corresponding viruses. Thus antiviral systems are essential in all living organisms. Remnants of virus derived information are also found in all life forms but have historically been considered mostly as junk DNA. However, such virus derived information can strongly affect host susceptibility to viruses. In this review, I evaluate the role viruses have had in the origin and evolution of host antiviral systems. From Archaea through bacteria and from simple to complex eukaryotes I trace the viral components that became essential elements of antiviral immunity. I conclude with a reexamination of the 'Big Bang' theory for the emergence of the adaptive immune system in vertebrates by horizontal transfer and note how viruses could have and did provide crucial and coordinated features.

  18. Impact of combination antiretroviral therapy initiation on adherence to antituberculosis treatment

    Directory of Open Access Journals (Sweden)

    Marlene Knight

    2015-04-01

    Full Text Available Background: Healthcare workers are often reluctant to start combination antiretroviral therapy (ART in patients receiving tuberculosis (TB treatment because of the fear of high pill burden, immune reconstitution inflammatory syndrome, and side-effects.Object: To quantify changes in adherence to tuberculosis treatment following ART initiation.Design: A prospective observational cohort study of ART-naïve individuals with baseline CD4 count between 50 cells/mm3 and 350 cells/mm3 at start of TB treatment at a primary care clinic in Johannesburg, South Africa. Adherence to TB treatment was measured by pill count,self-report, and electronic Medication Event Monitoring System (eMEMS before and after initiation of ART.Results: ART tended to negatively affect adherence to TB treatment, with an 8% – 10% decrease in the proportion of patients adherent according to pill count and an 18% – 22% decrease in the proportion of patients adherent according to eMEMS in the first month following ART initiation, independent of the cut-off used to define adherence (90%, 95% or 100%. Reasons for non-adherence were multi factorial, and employment was the only predictor for optimal adherence (adjusted odds ratio 4.11, 95% confidence interval 1.06–16.0.Conclusion: Adherence support in the period immediately following ART initiation could optimise treatment outcomes for people living with TB and HIV.

  19. Review of recent research progress in correlating HBV genotypes with efficacy of antiviral treatments%乙型肝炎病毒基因型与抗病毒药物疗效关系的研究进展

    Institute of Scientific and Technical Information of China (English)

    邓乐

    2012-01-01

    Hepatitis B is one of the most prevalent infectious diseases worldwide. Moreover, chronic hepatitis B virus ( HBV) infection is strongly associated with subsequent development of life - threatening hepatic diseases, such as heptocellular carcinoma, decompensated cirrhosis, and advanced fibrosis. Extensive studies of the various HBV genotypes have uncovered a close correlated with clinical factors, which may help to design and implement effective therapeutic strategies for treating infections with the different genotypes. Since antivirus therapy remains the main treatment for hepatitis B, research studies have focused on determining the relations between the various HBV genotypes and efficacy of the currently available antiviral drugs. In this review, we systematically discuss the recent findings from the literature on HBV genotype correlations with efficacy of antivirus treatment.%乙型肝炎在全球发病率高,严重危害人类健康.随着HBV基因型研究的深入,大量研究显示HBV基因型与临床疾病谱密切相关.目前抗病毒治疗是慢性乙型肝炎治疗的最主要措施,越来越多的学者对HBV基因型与抗病毒药物疗效的关系进行了研究,本文就目前国内外关于HBV基因型与抗病毒疗效关系的研究进展作一综述.

  20. Antiviral efficacy of adefovir dipivoxil versus lamivudine in patients with chronic hepatitis B sequentially treated with lamivudine and adefovir due to lamivudine resistance

    Institute of Scientific and Technical Information of China (English)

    Yeon Seok Seo; Ji Hoon Kim; Jong Eun Yeon; Jong-Jae Park; Jae Seon Kim; Kwan Soo Byun; Young-Tae Bak; Chang Hong Lee

    2007-01-01

    AIM: To compare the antiviral efficacy of adefovir (ADV) in lamivudine (LMV)-resistant patients with LMV treatment in nucleoside-na(i)ve patients, using serum samples collected sequentially during the course of treatment progressing from LMV to ADV.METHODS: Forty-four patients with chronic hepatitis B (CHB) were included. The patients were initially treated with LMV and then switched to ADV when LMV resistance developed. Antiviral efficacy was assessed by measuring the following: reduction in serum HBV DNA from baseline, HBV DNA negative conversion (defined as HBV DNA being undectable by the hybridization assay),and HBV DNA response (either HBV DNA level ≤ 105 copies/mL or a ≥ 2 log10 reduction from baseline HBV DNA level).RESULTS: After two and six months of treatment, HBV DNA reduction was greater with LMV compared to ADV treatment (P = 0.021). HBV DNA negative conversion rates were 64% and 27% after one month of LMV and ADV treatment respectively (P = 0.001). Similarly, HBV DNA response rates were 74% and 51% after two months of LMV and ADV treatment respectively (P = 0.026).The time taken to HBV DNA negative conversion and to HBV DNA response were both delayed in ADV treatment compared with LMV.CONCLUSION: The antiviral efficacy of ADV in LMV-resistant patients is slower and less potent than that with LMV in nucleoside-na(i)ve patients during the early course of treatment.

  1. Cognitive Behavioral Treatment of Panic Disorder and Agoraphobia in a Multiethnic Urban Outpatient Clinic: Initial Presentation and Treatment Outcome

    Science.gov (United States)

    Friedman, Steven; Braunstein, Jeffrey W.; Halpern, Beth

    2006-01-01

    Few studies examine the effectiveness of panic control treatment across diverse ethnic groups. In this paper we present data on 40 patients (African American, n = 24; Caucasian, n = 16) with panic disorder and comorbid agoraphobia who presented at an anxiety disorder clinic in an inner-city area. On initial assessment both groups were similar on…

  2. A controlled trial of flumazenil and gabapentin for initial treatment of methylamphetamine dependence.

    Science.gov (United States)

    Urschel, Harold C; Hanselka, Larry L; Baron, Michael

    2011-02-01

    Drug use has been associated with craving, which may be described as a powerful and sometimes overwhelming urge to use the drug. Patients seeking treatment for methylamphetamine dependence must cope with drug cravings as they engage in psychosocial treatments. Changes in brain GABA(A) receptors during substance use and withdrawal provide a neurobiological basis for craving and associated anxiety. Flumazenil (a benzodiazepine antagonist) plus gabapentin (an antiepileptic) were compared with placebo in a randomized, double-blind study to assess the effects on craving during initial treatment for methylamphetamine dependence. Evaluation was conducted over a 30-day period. Craving and drug use were found to be highly correlated. Craving was reduced significantly in the flumazenil plus gabapentin group compared with placebo following the initial treatment period and throughout the 30 days. Decreased methylamphetamine use was also observed, as measured by urine drug screens and self-reports.

  3. Influenza Round Table: Antiviral Drugs

    Centers for Disease Control (CDC) Podcasts

    2009-11-04

    In this podcast, Dr. Joe Bresee explains the nature of antiviral drugs and how they are used.  Created: 11/4/2009 by National Center for Immunization and Respiratory Diseases (NCIRD).   Date Released: 11/4/2009.

  4. Antiviral, antifungal and antiprotozoal agents in the cinema.

    Science.gov (United States)

    García-Sánchez, Jose Elias; García-Sánchez, E; Merino Marcos, M L

    2007-03-01

    Among the antimicrobial agents, antibacterials are the most frequently mentioned in cinematographic plots. Nevertheless, it is not uncommon to come across other antiviral agents, especially antiretrovirals and antiprotozoals. We analyzed the presence of antiviral and antifungal agents in different commercial films, both when they were merely mentioned in passing and when they played a major role in the film. This review essentially aims to address the historical portrayal of these agents in film and to list their appearances. The fictional treatments that appear in some films are not addressed.

  5. Initial non-responders to ranibizumab in the treatment of age-related macular degeneration (AMD

    Directory of Open Access Journals (Sweden)

    Otsuji T

    2013-07-01

    Full Text Available Tsuyoshi Otsuji,1 Yoshimi Nagai,2 Kenichiro Sho,1 Akiko Tsumura,1 Naoko Koike,1 Mei Tsuda,1 Tetsuya Nishimura,1 Kanji Takahashi2 1Department of Ophthalmology, Kansai Medical University, Takii Hospital, Osaka, Japan; 2Department of Ophthalmology, Kansai Medical University, Hirakata Hospital, Osaka, Japan Background: Patients with exudative age-related macular degeneration (AMD who did not respond to ranibizumab at the induction phase were assessed and referred to as initial non-responders. Methods: We retrospectively reviewed the medical records of 215 patients (218 eyes with exudative AMD. For the initial treatments, patients received three intravitreal injections of ranibizumab (IVR every 4 weeks. Minimum follow-up period was 12 months. We defined patients with no improvement of best corrected logMAR visual acuity (BCVA, and with no decrease of central retinal thickness (CRT at the end of the initial treatment, as initial non-responders. Patients who had previous treatment history prior to this investigation were included, but patients who had photodynamic therapy (PDT with IVR were excluded. Results: Twenty-two eyes (10.1% were identified as initial non-responders. The mean BCVA of initial non-responders before IVR and after induction phase were 0.39 and 0.36, respectively. There was no significant difference between these values, however the mean BCVA decreased significantly to 0.55 at 12 months after the beginning of the induction phase (P = 0.021. The mean greatest linear dimension (GLD of the lesion before IVR of initial non-responders was 4,121 µm. We found 16 eyes with typical AMD, and six eyes with polypoidal choroidal vasculopathy. One eye had predominantly classic choroidal neovascularization (CNV, and others had occult CNV of typical AMD. As additional treatments, twelve eyes received PDT, and in three of the eyes exudation remained after PDT. Conclusion: Initial non-responders were more prevalent in patients with occult CNV than in

  6. Learning from the Messengers: Innate Sensing of Viruses and Cytokine Regulation of Immunity — Clues for Treatments and Vaccines

    Directory of Open Access Journals (Sweden)

    Jesper Melchjorsen

    2013-01-01

    Full Text Available Virus infections are a major global public health concern, and only via substantial knowledge of virus pathogenesis and antiviral immune responses can we develop and improve medical treatments, and preventive and therapeutic vaccines. Innate immunity and the shaping of efficient early immune responses are essential for control of viral infections. In order to trigger an efficient antiviral defense, the host senses the invading microbe via pattern recognition receptors (PRRs, recognizing distinct conserved pathogen-associated molecular patterns (PAMPs. The innate sensing of the invading virus results in intracellular signal transduction and subsequent production of interferons (IFNs and proinflammatory cytokines. Cytokines, including IFNs and chemokines, are vital molecules of antiviral defense regulating cell activation, differentiation of cells, and, not least, exerting direct antiviral effects. Cytokines shape and modulate the immune response and IFNs are principle antiviral mediators initiating antiviral response through induction of antiviral proteins. In the present review, I describe and discuss the current knowledge on early virus–host interactions, focusing on early recognition of virus infection and the resulting expression of type I and type III IFNs, proinflammatory cytokines, and intracellular antiviral mediators. In addition, the review elucidates how targeted stimulation of innate sensors, such as toll-like receptors (TLRs and intracellular RNA and DNA sensors, may be used therapeutically. Moreover, I present and discuss data showing how current antimicrobial therapies, including antibiotics and antiviral medication, may interfere with, or improve, immune response.

  7. The Antiviral Effect of Baicalin on Enterovirus 71 In Vitro

    Directory of Open Access Journals (Sweden)

    Xiang Li

    2015-08-01

    Full Text Available Baicalin is a flavonoid compound extracted from Scutellaria roots that has been reported to possess antibacterial, anti-inflammatory, and antiviral activities. However, the antiviral effect of baicalin on enterovirus 71 (EV71 is still unknown. In this study, we found that baicalin showed inhibitory activity on EV71 infection and was independent of direct virucidal or prophylactic effect and inhibitory viral absorption. The expressions of EV71/3D mRNA and polymerase were significantly blocked by baicalin treatment at early stages of EV71 infection. In addition, baicalin could decrease the expressions of FasL and caspase-3, as well as inhibit the apoptosis of EV71-infected human embryonal rhabdomyosarcoma (RD cells. Altogether, these results indicate that baicalin exhibits potent antiviral effect on EV71 infection, probably through inhibiting EV71/3D polymerase expression and Fas/FasL signaling pathways.

  8. Patient-initiated second opinions: systematic review of characteristics and impact on diagnosis, treatment, and satisfaction.

    Science.gov (United States)

    Payne, Velma L; Singh, Hardeep; Meyer, Ashley N D; Levy, Lewis; Harrison, David; Graber, Mark L

    2014-05-01

    The impact of second opinions on diagnosis in radiology and pathology is well documented; however, the value of patient-initiated second opinions for diagnosis and treatment in general medical practice is unknown. We conducted a systematic review of patient-initiated second opinions to assess their impact on clinical outcomes and patient satisfaction and to determine characteristics and motivating factors of patients who seek a second opinion. We searched PubMed, EMBASE, Cochrane, and Academic OneFile databases using Medical Subject Headings (MeSH) indexes and keyword searches. Search terms included referral and consultation, patient-initiated, patient preference, patient participation, second opinion, second review, and diagnosis. Multiple reviewers screened abstracts and articles to determine eligibility and extract data. We assessed risk of bias using the Cochrane Risk of Bias Tool and rated study quality using Cochrane's GRADE (Grades of Recommendation, Assessment, Development and Evaluation) approach. We screened 1342 abstracts and reviewed full text of 41 articles, identifying 7 articles that reported clinical agreement data and 10 that discussed patient characteristics, motivation, and satisfaction. We found that a second opinion typically confirms the original diagnosis or treatment regimen but that 90% of patients with poorly defined conditions remain undiagnosed. However, 10% to 62% of second opinions yield a major change in the diagnosis, treatment, or prognosis. A larger fraction of patients receive different advice on treatment than on diagnosis. Factors motivating a second opinion include diagnosis or treatment confirmation, dissatisfaction with a consultation, desire for more information, persistent symptoms, or treatment complications. Patients generally believed that second opinions were valuable. Second opinions can result in diagnostic and treatment differences. The literature on patient-initiated second opinions is limited, and the accuracy of

  9. Initiation and persistence with clopidogrel treatment after acute myocardial infarction: a nationwide study

    DEFF Research Database (Denmark)

    Abildstrøm, Steen Zabell; Sørensen, Rikke; Gislason, G H

    2008-01-01

    AIMS: To identify possible underuse by analysing initiation and persistence with clopidogrel treatment in an unselected population of patients admitted with myocardial infarction (MI) with or without subsequent percutaneous coronary intervention (PCI). METHODS: Patients admitted with first-time MI...... from 2000 to 2005 and subsequent prescription claims of clopidogrel were identified by individual-level linkage of nationwide administrative registries in Denmark. Independent factors affecting initiation and persistence with treatment were analysed by multivariable logistic regression models and Cox...... proportional hazard models. RESULTS: A total of 46,190 MI patients were included in the study, of whom 14,939 were treated with PCI. From 2000 to 2005 initiation of clopidogrel increased from 80.4 to 93.7% among MI patients with PCI and from 2.8 to 39.3% among MI patients without PCI. MI patients...

  10. Differences in durability of treatment with initial PI-based regimens.

    Science.gov (United States)

    Pérez-Elías, Maria Jesús; Moreno, Ana; Moreno, Santiago; Antela, Antonio; Dronda, Fernando; Muñoz, Vicente; Casado, Jose Luis; Quereda, Carmen; Lopez, Dolores; Navas, Enrique

    2003-01-01

    The durability of virologic response to antiretroviral therapy is dependent on the potency, tolerability, and adherence level of the regimen. In a prospective, nonrandomized cohort study, we compared the treatment outcome of a nelfinavir-based highly active antiretroviral therapy (HAART) regimen with that of an indinavir-based regimen, over 1 year of routine clinical practice. Information was derived from 134 treatment-naïve HIV-1-infected patients initiated on triple therapy with either nelfinavir (n = 44) or indinavir (n = 90). The proportions of patients achieving a virological response were similar between treatment groups (>1 log(10) reduction in HIV RNA at 3 months in 95% of patients taking nelfinavir and 88% taking indinavir; HIV RNA 90% (p =.0001). Over 90% adherence was achieved in 70% of patients taking nelfinavir compared with 41% of those taking indinavir (p =.01). The probability of remaining on the initial protease inhibitor (PI) after 12 months was 77% in the nelfinavir group and 66% in the indinavir group, with the median time to changing treatment being 519 days and 462 days, respectively. Gastric intolerance and nephritic colic were the most common reasons for changing therapy in the indinavir group. In the clinical setting, HAART based on initial nelfinavir and indinavir therapy was associated with similarly good virological and immunological suppression at 1 year, however, nelfinavir-based treatment was associated with a longer durability, probably due to a better adherence and tolerance pattern.

  11. Hepatitis C virus: Virology, diagnosis and management of antiviral therapy

    Institute of Scientific and Technical Information of China (English)

    Stéphane Chevaliez; Jean-Michel Pawlotsky

    2007-01-01

    Hepatitis C virus (HCV) infects approximately 170 million individuals worldwide. Prevention of HCV infection complications is based on antiviral therapy with the combination of pegylatecl interferon alfa and ribavirin.The use of serological and virological tests has become essential in the management of HCV infection in order to diagnose infection, guide treatment decisions and assess the virological response to antiviral therapy. Anti-HCV antibody testing and HCV RNA testing are used to diagnose acute and chronic hepatitis C. The HCV genotype should be systematically determined before treatment, as it determines the indication, the duration of treatment,the dose of ribavirin and the virological monitoring procedure. HCV RNA monitoring during therapy is used to tailor treatment duration in HCV genotype 1 infection, and molecular assays are used to assess the end-of-treatment and, most importantly the sustained virological response,i.e. the enlpoint of therapy.

  12. Antiviral effect of methylated flavonol isorhamnetin against influenza.

    Science.gov (United States)

    Abdal Dayem, Ahmed; Choi, Hye Yeon; Kim, Young Bong; Cho, Ssang-Goo

    2015-01-01

    Influenza is an infectious respiratory disease with frequent seasonal epidemics that causes a high rate of mortality and morbidity in humans, poultry, and animals. Influenza is a serious economic concern due to the costly countermeasures it necessitates. In this study, we compared the antiviral activities of several flavonols and other flavonoids with similar, but distinct, hydroxyl or methyl substitution patterns at the 3, 3', and 4' positions of the 15-carbon flavonoid skeleton, and found that the strongest antiviral effect was induced by isorhamnetin. Similar to quercetin and kaempferol, isorhamnetin possesses a hydroxyl group on the C ring, but it has a 3'-methyl group on the B ring that is absent in quercetin and kaempferol. Co-treatment and pre-treatment with isorhamnetin produced a strong antiviral effect against the influenza virus A/PR/08/34(H1N1). However, isorhamnetin showed the most potent antiviral potency when administered after viral exposure (post-treatment method) in vitro. Isorhamnetin treatment reduced virus-induced ROS generation and blocked cytoplasmic lysosome acidification and the lipidation of microtubule associated protein1 light chain 3-B (LC3B). Oral administration of isorhamnetin in mice infected with the influenza A virus significantly decreased lung virus titer by 2 folds, increased the survival rate which ranged from 70-80%, and decreased body weight loss by 25%. In addition, isorhamnetin decreased the virus titer in ovo using embryonated chicken eggs. The structure-activity relationship (SAR) of isorhamnetin could explain its strong anti-influenza virus potency; the methyl group located on the B ring of isorhamnetin may contribute to its strong antiviral potency against influenza virus in comparison with other flavonoids.

  13. Antiviral effect of methylated flavonol isorhamnetin against influenza.

    Directory of Open Access Journals (Sweden)

    Ahmed Abdal Dayem

    Full Text Available Influenza is an infectious respiratory disease with frequent seasonal epidemics that causes a high rate of mortality and morbidity in humans, poultry, and animals. Influenza is a serious economic concern due to the costly countermeasures it necessitates. In this study, we compared the antiviral activities of several flavonols and other flavonoids with similar, but distinct, hydroxyl or methyl substitution patterns at the 3, 3', and 4' positions of the 15-carbon flavonoid skeleton, and found that the strongest antiviral effect was induced by isorhamnetin. Similar to quercetin and kaempferol, isorhamnetin possesses a hydroxyl group on the C ring, but it has a 3'-methyl group on the B ring that is absent in quercetin and kaempferol. Co-treatment and pre-treatment with isorhamnetin produced a strong antiviral effect against the influenza virus A/PR/08/34(H1N1. However, isorhamnetin showed the most potent antiviral potency when administered after viral exposure (post-treatment method in vitro. Isorhamnetin treatment reduced virus-induced ROS generation and blocked cytoplasmic lysosome acidification and the lipidation of microtubule associated protein1 light chain 3-B (LC3B. Oral administration of isorhamnetin in mice infected with the influenza A virus significantly decreased lung virus titer by 2 folds, increased the survival rate which ranged from 70-80%, and decreased body weight loss by 25%. In addition, isorhamnetin decreased the virus titer in ovo using embryonated chicken eggs. The structure-activity relationship (SAR of isorhamnetin could explain its strong anti-influenza virus potency; the methyl group located on the B ring of isorhamnetin may contribute to its strong antiviral potency against influenza virus in comparison with other flavonoids.

  14. Caries preventive efficiency of therapeutic complex accomponying orthodontic treatment of children with initial dental caries

    Directory of Open Access Journals (Sweden)

    Denga A.E.

    2013-12-01

    Full Text Available The use of orthodontic non-removable appliance in orthodontic treatment inter¬feres with the process of teeth mineralization, worsens level of oral cavity hygiene, stimulates development of caries process. The situation is complicated when a patient has an initial tooth decay. The aim of this study was to determine genetic characteristics of children with initial caries and clinical evaluation of effectiveness of the developed caries preventive therapeutic complex accompanying treatment of jaw facial anomalies (JFA. 47 children aged 12-14 with initial tooth decay participated in the examination. Complex diagnostics, including molecular genetic studies was carried out. Therapeutic complex for children, of the main group included remineralizing, adaptogenic, biogenic agents, which increase non-specific resistance, as well as infiltration ICON therapy before fixing braces. Caries preventive complex accompanying JFA treatment in children with primary tooth decay developed with regard to revealed genetic disorders of amelogenesis, 2-nd of phase detoxification, collagen formation, functional responses in the oral cavity, state of hard tissues of teeth and periodontal tissues enabled to preserve existing carious process, normalize periodontal and hygienic indices at all stages of treatment.

  15. Spectroscopic investigation of herpes simplex viruses infected cells and their response to antiviral therapy

    Science.gov (United States)

    Erukhimovitch, Vitaly; Talyshinsky, Marina; Souprun, Yelena; Huleihel, Mahmoud

    2006-07-01

    In the present study, we used microscopic Fourier transform infrared spectroscopy (FTIR) to evaluate the antiviral activity of known antiviral agents against herpes viruses. The antiviral activity of Caffeic acid phenethyl ester (CAPE) (which is an active compound of propolis) against herpes simplex type 1 and 2 was examined in cell culture. The advantage of microscopic FTIR spectroscopy over conventional FTIR spectroscopy is that it facilitates inspection of restricted regions of cell culture or tissue. Our results showed significant spectral differences at early stages of infection between infected and non-infected cells, and between infected cells treated with the used antiviral agent and those not treated. In infected cells, there was a considerable increase in phosphate levels. Our results show that treatment with used antiviral agent considerably abolish the spectral changes induced by the viral infection. In addition, it is possible to track by FTIR microscopy method the deferential effect of various doses of the drug.

  16. Recent advances in antiviral therapy.

    OpenAIRE

    Kinchington, D

    1999-01-01

    In the early 1980s many institutions in Britain were seriously considering whether there was a need for specialist departments of virology. The arrival of HIV changed that perception and since then virology and antiviral chemotherapy have become two very active areas of bio-medical research. Cloning and sequencing have provided tools to identify viral enzymes and have brought the day of the "designer drug" nearer to reality. At the other end of the spectrum of drug discovery, huge numbers of ...

  17. Dasatinib and Doxorubicin Treatment of Sarcoma Initiating Cells: A Possible New Treatment Strategy

    DEFF Research Database (Denmark)

    Aggerholm-Pedersen, Ninna; Demouth, Christina; Safwat, Akmal;

    2016-01-01

    growth factor receptor (EGFR) was activated in both cell lines. However hMSC-TERT20-CE8 exhibited significantly higher expression of the EGFR ligands. EGFR inhibitors such as erlotinib and afatinib alone or in combination with doxorubicin failed to further decrease cell viability of hMSC-TERT20-CE8......) stem cell line hMSC-TERT4 and a transformed cell line hMSC-TERT20-CE8, known to form sarcoma-like tumours when implanted in immune-deficient mice, were used as models. Receptor tyrosine kinase (RTK) activation was analysed by RTK arrays and cellular viability after tyrosine kinases inhibitor (TKI....... However, inhibition with the TKI dasatinib in combination with doxorubicin decreased cell viability of the hMSC-TERT20-CE8 cell line. Conclusion. Our results demonstrate that dasatinib, but not EGFR-directed treatment, can decrease cell viability of stromal cancer stem cells less sensitive to doxorubicin....

  18. [Renal toxicity of antiviral drugs].

    Science.gov (United States)

    Frasca', Giovanni M; Balestra, Emilio; Tavio, Marcello; Morroni, Manrico; Manarini, Gloria; Brigante, Fabiana

    2012-01-01

    Highly effective and powerful antiviral drugs have been introduced into clinical practice in recent years which are associated with an increased incidence of nephrotoxicity. The need of combining several drugs, the fragility of the patients treated, and the high susceptibility of the kidney are all factors contributing to renal injury. Many pathogenetic mechanisms are involved in the nephrotoxicity of antiviral drugs, including drug interaction with transport proteins in the tubular cell; direct cytotoxicity due to a high intracellular drug concentration; mitochondrial injury; and intrarenal obstruction or stone formation due to the low solubility of drugs at a normal urinary pH. As a result, various clinical pictures may be observed in patients treated with antiviral drugs, ranging from tubular dysfunction (Fanconi syndrome, renal tubular acidosis, nephrogenic diabetes insipidus) to acute renal failure (induced by tubular necrosis or crystal nephropathy) and kidney stones. Careful attention should be paid to prevent renal toxicity by evaluating the glomerular filtration rate before therapy and adjusting the drug dosage accordingly, avoiding the combination with other nephrotoxic drugs, and monitoring renal parameters on a regular basis while treating patients.

  19. The influence of hepatitis B virus on antiviral treatment with interferon and ribavirin in Asian patients with hepatitis C virus/hepatitis B virus coinfection: a meta-analysis

    Directory of Open Access Journals (Sweden)

    Liu Jun-Ying

    2012-09-01

    Full Text Available Abstract Background Clinical and laboratory studies have indicated that coinfection with hepatitis B virus (HBV and hepatitis C virus (HCV can suppress one another, eliciting a dominant disease phenotype. To assess whether HBV can influence the antiviral effect of treatment on HCV, we performed a meta-analysis to comparatively analyze the response to interferon plus ribavirin treatment in patients with HBV/HCV coinfection and HCV mono-infection. Methods Published studies in the English-language medical literature that involved cohorts of HBV/HCV coinfection and HCV mono-infection were obtained by searching Medline, Cochrane and Embase databases. Studies that compared the efficacy of treatment with interferon plus ribavirin in HBV/HCV coinfection and HCV mono-infection were assessed. End-of-treatment virological response (ETVR, sustained virological response (SVR, HCV relapse rate, and alanine aminotransferase (ALT normalization rate were compared between HBV/HCV coinfection and HCV mono-infection patients. Results Five trials involving 705 patients were analyzed. At the end of follow-up serum ALT normalization rates in patients with HCV mono-infection were significantly higher than in patients with HBV/HCV coinfection (odds ratio (OR = 0.56, 95% confidence interval (CI: 0.40–0.80, P = 0.001. The ETVR and SVR achieved in HBV/HCV coinfection patients were comparable to those in HCV mono-infection patients (OR = 1.03, 95% CI: 0.37–2.82, P = 0.96 and OR = 0.87, 95% CI: 0.62–1.21, P = 0.38, respectively. The rate of relapse for HCV or HCV genotype 1 was not significantly different between HBV/HCV coinfection patients and HCV mono-infection patients (OR = 1.55, 95% CI: 0.98–2.47, P = 0.06; HCV genotype 1: OR = 2.4, 95% CI: 1.17–4.91, P = 0.19. Conclusions Treatment with interferon and ribavirin achieves similar ETVR and SVR in HBV/HCV coinfection and HCV mono-infection. HBV/HCV coinfection patients had

  20. Modeling AIDS survival after initiation of antiretroviral treatment by Weibull models with changepoints

    Directory of Open Access Journals (Sweden)

    Yiannoutsos Constantin T

    2009-06-01

    Full Text Available Abstract Background Mortality of HIV-infected patients initiating antiretroviral therapy in the developing world is very high immediately after the start of ART therapy and drops sharply thereafter. It is necessary to use models of survival time that reflect this change. Methods In this endeavor, parametric models with changepoints such as Weibull models can be useful in order to explicitly model the underlying failure process, even in the case where abrupt changes in the mortality rate are present. Estimation of the temporal location of possible mortality changepoints has important implications on the effective management of these patients. We briefly describe these models and apply them to the case of estimating survival among HIV-infected patients who are initiating antiretroviral therapy in a care and treatment programme in sub-Saharan Africa. Results As a first reported data-driven estimate of the existence and location of early mortality changepoints after antiretroviral therapy initiation, we show that there is an early change in risk of death at three months, followed by an intermediate risk period lasting up to 10 months after therapy. Conclusion By explicitly modelling the underlying abrupt changes in mortality risk after initiation of antiretroviral therapy we are able to estimate their number and location in a rigorous, data-driven manner. The existence of a high early risk of death after initiation of antiretroviral therapy and the determination of its duration has direct implications for the optimal management of patients initiating therapy in this setting.

  1. Resistance mutations and CTL epitopes in archived HIV-1 DNA of patients on antiviral treatment: toward a new concept of vaccine.

    Directory of Open Access Journals (Sweden)

    Jennifer Papuchon

    Full Text Available Eleven patients responding successfully to first-line antiretroviral therapy (ART were investigated for proviral drug resistance mutations (DRMs in RT by ultra-deep pyrosequencing (UDPS. After molecular typing of the class I alleles A and B, the CTL epitopes in the Gag, Nef and Pol regions of the provirus were sequenced and compared to the reference HXB2 HIV-1 epitopes. They were then matched with the HLA alleles with determination of theoretical affinity (TA. For 3 patients, the results could be compared with an RNA sample of the circulating virus at initiation of therapy. Five out of 11 patients exhibited DRMs by UDPS. The issue is whether a therapeutic switch is relevant in these patients by taking into account the identity of the archived resistance mutations. When the archived CTL epitopes were determined on the basis of the HLA alleles, different patterns were observed. Some epitopes were identical to those reported for the reference with the same TA, while others were mutated with a decrease in TA. In 2 cases, an epitope was observed as a combination of subpopulations at entry and was retrieved as a single population with lower TA at success. With regard to immunological stimulation and given the variability of the archived CTL epitopes, we propose a new concept of curative vaccine based on identification of HIV-1 CTL epitopes after prior sequencing of proviral DNA and matching with HLA class I alleles.

  2. Antiviral Effect Assay of Aqueous Extract of Echium Amoenum-L against HSV-1

    Directory of Open Access Journals (Sweden)

    Malihe Farahani

    2013-08-01

    Full Text Available Background: Medicinal plants have been used for different diseases in past. There is an increasing need for substances with antiviral activity since the treatment of viral infections with the available antiviral drugs often leads to the problem of viral resistance. Therefore in the present study Echium amoenum L plant with ethnomedical background was screened for antiviral activity against HSV-1 in different times. Materials and Methods: Flower part of Echium amoenum L plant collected from Iran was extracted with different methods to obtain crude aqueous extract. This extract was screened for its cytotoxicity against Hep II cell line by CPE assay. Antiviral properties of the plant extract were determined by cytopathic effect inhibition assay.Results: Echium amoenum L extract exhibited significant antiviral activity at non toxic concentrations to the cell line used. Findings indicated that plant extract has the most antiviral activity when it used an hour after virus inoculation.Conclusion: Echium amoenum L plant had not toxic effect at highest concentrations to the cell lines used and showed the most antiviral activity when it used an hour after virus inoculation. Further research is needed to elucidate the active constituents of this plant which may be useful in the development of new and effective antiviral agents.

  3. The Safety of Hezhou Antiviral Treatment in Patients with HIV/AIDS Research%贺州市艾滋病患者抗病毒治疗的安全性研究

    Institute of Scientific and Technical Information of China (English)

    李晓云; 莫耀素; 严汝庆; 陈强文; 李金卓; 李鑫; 陈柳林; 黄荣道; 刘燕飞; 李繁

    2015-01-01

    目的:了解贺州市HIV/AIDS患者接受抗病毒治疗后90 d内药物不良反应(ADR)发生的规律及其影响因素,评价HIV/AIDS患者抗病毒治疗的安全性。方法对160例HIV/AIDS患者接受抗病毒治疗进行为期90 d的ADR监测,记录抗病毒药物ADR的发生时间、发生类型、ADR主要表现、干预措施和转归等。结果160例接受抗病毒治疗的HIV/AIDS患者中,ADR的发生率为95.0%;累及系统器官主要有:代谢和营养障碍60.0%、全身性损害57.5%、血液系统45.6%、胃肠系统18.8%、肝胆系统26.9%、皮肤及其附件18.1%、神经系统18.8%等;累计出现ADR共517例次,结果痊愈或好转65.0%、未好转23.6%,不详11.4%;75.4%的ADR未采取干预措施;因ADR导致更换治疗方案的30例,停药3例。结论贺州市HIV/AIDS患者抗病毒治疗后90 d内ADR发生率高,多数ADR症状轻微,部分ADR经对症处理后可好转或痊愈,临床医生应对治疗患者进行定期回访,对治疗中出现的ADR及时给予相应的干预措施,以提高患者用药的依从性,保证治疗效果和用药的安全性。%Objective The purpose of this thesis is to detect the adverse drug reaction (ADR) and its influencing factors on HIV/AIDS patients after their receiving antiretroviral treatment in the city of Hezhou within 90 days, so as to evaluate the safety of antiviral therapy in patients with HIV/AIDS. Methods This study based on 160 cases of HIV/AIDS patients who have received antiretroviral therapy under a 90-day ADR monitoring, during which the time, types, ADR main perfor-mances, interventions, and also the outcome of antiviral drug ADR have been recorded. Results In 160 cases of HIV/AIDS patients receiving antiretroviral therapy, the ADR incidence rate is 95%; Organs involved in ADR and its clinical mani-festos are:60% among which are the metabolic and nutritional disorders, 57.5%overall systemic damage to the whole body;45.6%of blood system;26

  4. COMPARISON OF ANTIRETROVIRAL SCHEMES USED IN INITIAL THERAPY FOR TREATMENT OF HIV/AIDS

    Directory of Open Access Journals (Sweden)

    Luana LENZI

    2015-12-01

    Full Text Available A problem of highly active antiretroviral therapy (HAART in HIV patients is their adherence to treatment. The aim of this study was to compare the schemes adopted in the initial therapy of these treatments with their adherence, changes in HAART schemes and treatment costs. The study included patients over 16 years old, HIV positive, in treatment for more than 30 days. Adherence to HAART was calculated based on the withdrawal of the drug, which was related to the total treatment time. We evaluated how many patients changed HAART. The costs of each regimen were also estimated and related to the benefit of each treatment. 142 patients who were between 38 and 1,150 days of treatment were included (57.7% women. The schemes with lower costs, highest adherence and greater benefit were efavirenz with biovir and efavirenz with lamivudine and tenofovir. This study suggested the advantageous therapeutic regimens to start of treatment, both from the point of view of patients and the health system. This information can serve as a subsidy to clinicians in the decision of starting HAART.

  5. Antiviral effect of mefloquine on feline calicivirus in vitro.

    Science.gov (United States)

    McDonagh, Phillip; Sheehy, Paul A; Fawcett, Anne; Norris, Jacqueline M

    2015-04-17

    Feline calicivirus (FCV) is an important viral pathogen of domestic cats causing clinical signs ranging from mild to severe oral ulceration or upper respiratory tract disease through to a severe fatal systemic disease. Current therapeutic options are limited, with no direct acting antivirals available for treatment. This study screened a panel of 19 compounds for potential antiviral activity against FCV strain F9 and recent field isolates in vitro. Using a resazurin-based cytopathic effect (CPE) inhibition assay, mefloquine demonstrated a marked inhibitory effect on FCV induced CPE, albeit with a relatively low selectivity index. Orthogonal assays confirmed inhibition of CPE was associated with a significant reduction in viral replication. Mefloquine exhibited a strong inhibitory effect against a panel of seven recent FCV isolates from Australia, with calculated IC50 values for the field isolates approximately 50% lower than against the reference strain FCV F9. In vitro combination therapy with recombinant feline interferon-ω, a biological response modifier currently registered for the treatment of FCV, demonstrated additive effects with a concurrent reduction in the IC50 of mefloquine. These results are the first report of antiviral effects of mefloquine against a calicivirus and support further in vitro and in vivo evaluation of this compound as an antiviral therapeutic for FCV.

  6. John F. Enders lecture 2006: antivirals for influenza.

    Science.gov (United States)

    Ong, Adrian K; Hayden, Frederick G

    2007-07-15

    The long history of influenza drug development has both contributed practical advances in antiviral chemotherapy and improved the understanding of influenza pathogenesis and epidemiology. The role played by these antivirals continues to grow with the dual threats of seasonal and pandemic influenza. The neuraminidase inhibitors are proven effective for the chemoprophylaxis and treatment of influenza A and B, although early therapy is essential for disease mitigation. Studies of topically applied zanamivir have demonstrated the importance of viral replication in the lower respiratory tract, even in uncomplicated influenza. Antiviral resistance, especially to the M2 ion channel inhibitors, sometimes limits clinical utility. Oseltamivir-resistant variants may emerge during treatment but have not yet circulated widely and are usually less fit than wild-type virus; most retain susceptibility to zanamivir. The transmission fitness cost of these resistant variants is drug-, neuraminidase subtype-, and mutation-specific. Continued vigilance in drug resistance surveillance is imperative, as is research into the development of new agents that will provide the potential for alternative and combination antiviral therapy.

  7. Roasting and aroma formation: effect of initial moisture content and steam treatment.

    Science.gov (United States)

    Baggenstoss, Juerg; Poisson, Luigi; Kaegi, Ruth; Perren, Rainer; Escher, Felix

    2008-07-23

    Initial moisture of green coffee may vary as a function of green coffee processing and storage conditions. The impact of initial moisture and steam treatment on roasting behavior and aroma formation was investigated. Steam treated coffees as well as coffees with initial moisture content of 5.10, 10.04, and 14.70 g water per 100 g wb were roasted. Light and dark roasting trials were carried out using a fluidizing-bed roaster with a batch size of 100 g of green beans. Differences in roast coffee attributes, that is, color, density, and organic roast loss, and odorant concentrations were more marked in light roasted than in dark roasted coffees. The results of roasting steam treated coffee suggest that this step affects roasting behavior primarily by extracting some aroma precursor compounds.

  8. Practical aspects of treatment with target specific anticoagulants: initiation, payment and current market, transitions, and venous thromboembolism treatment.

    Science.gov (United States)

    Mahan, Charles E

    2015-04-01

    Target specific anticoagulants (TSOACs) have recently been introduced to the US market for multiple indications including venous thromboembolism (VTE) prevention in total hip and knee replacement surgeries, VTE treatment and reduction in the risk of stroke in patients with non-valvular atrial fibrillation (NVAF). Currently, three TSOACs are available including rivaroxaban, apixaban, and dabigatran with edoxaban currently under Food and Drug Administration review for VTE treatment and stroke prevention in NVAF. The introduction of these agents has created a paradigm shift in anticoagulation by considerably simplifying treatment and anticoagulant initiation for patients by giving clinicians the opportunity to use a rapid onset, rapid offset, oral agent. The availability of these rapid onset TSOACs is allowing for outpatient treatment of low risk pulmonary embolism and deep vein thrombosis which can greatly reduce healthcare costs by avoiding inpatient hospitalizations and treatment for the disease. Additionally with this practice, the complications of an inpatient hospitalization may also be avoided such as nosocomial infections. Single-agent approaches with TSOACs represent a paradigm shift in the treatment of VTE versus the complicated overlap of a parenteral agent with warfarin. Transitions between anticoagulants, including TSOACs, are a high-risk period for the patient, and clinicians must carefully consider patient characteristics such as renal function as well as the agents that are being transitioned. TSOAC use appears to be growing slowly with improved payment coverage throughout the US.

  9. Suspected uncomplicated cecal diverticulitis diagnosed by imaging:Initial antibiotics vs laparoscopic treatment

    Institute of Scientific and Technical Information of China (English)

    Hyoung-Chul; Park; Bong; Hwa; Lee

    2010-01-01

    AIM:To compare the recurrence rate following initial antibiotic management to that following laparoscopic treatment for suspected uncomplicated cecal diverticulitis. METHODS: We examined the records of 132 patients who were diagnosed with uncomplicated cecal diverticulitis and a first attack during an 8-year period. The diagnosis of uncomplicated diverticulitis was made based on imaging findings, such as inflamed diverticulum or a phlegmon with cecal wall thickening. Concurrent appendiceal dilatation from 8...

  10. Early, patient-initiated treatment of herpes labialis with topical 10% acyclovir.

    OpenAIRE

    Spruance, S. L.; Crumpacker, C S; Schnipper, L E; Kern, E. R.; Marlowe, S; Arndt, K A; Overall, J C

    1984-01-01

    To determine whether topical acyclovir in polyethylene glycol could reduce the severity of herpes simplex labialis if applied immediately after onset of a recurrence, 10% acyclovir in polyethylene glycol ointment or polyethylene glycol alone was prospectively dispensed to 352 patients in a double-blind, randomized trial. Sixty-nine subjects initiated treatment in the prodrome (57%) or erythema (43%) stage and were followed by clinical and virological criteria. The healing time (6.0 days), max...

  11. Clinical and genetic determinants of warfarin pharmacokinetics and pharmacodynamics during treatment initiation.

    Directory of Open Access Journals (Sweden)

    Inna Y Gong

    Full Text Available Variable warfarin response during treatment initiation poses a significant challenge to providing optimal anticoagulation therapy. We investigated the determinants of initial warfarin response in a cohort of 167 patients. During the first nine days of treatment with pharmacogenetics-guided dosing, S-warfarin plasma levels and international normalized ratio were obtained to serve as inputs to a pharmacokinetic-pharmacodynamic (PK-PD model. Individual PK (S-warfarin clearance and PD (I(max parameter values were estimated. Regression analysis demonstrated that CYP2C9 genotype, kidney function, and gender were independent determinants of S-warfarin clearance. The values for I(max were dependent on VKORC1 and CYP4F2 genotypes, vitamin K status (as measured by plasma concentrations of proteins induced by vitamin K absence, PIVKA-II and weight. Importantly, indication for warfarin was a major independent determinant of I(max during initiation, where PD sensitivity was greater in atrial fibrillation than venous thromboembolism. To demonstrate the utility of the global PK-PD model, we compared the predicted initial anticoagulation responses with previously established warfarin dosing algorithms. These insights and modeling approaches have application to personalized warfarin therapy.

  12. New Inhibitors of the DENV-NS5 RdRp from Carpolepis laurifolia as Potential Antiviral Drugs for Dengue Treatment

    Directory of Open Access Journals (Sweden)

    Paul Coulerie

    2014-05-01

    Full Text Available Since a few decades the dengue virus became a major public health concern and no treatment is available yet. In order to propose potential antidengue compounds for chemotherapy we focused on DENV RNA polymerase (DENV-NS5 RdRp which is specific and essential for the virus replication. Carpolepis laurifolia belongs to the Myrtaceae and is used as febrifuge in traditional kanak medicine. Leaf extract of this plant has been identified as a hit against the DENV-NS5 RdRp. Here we present a bioguided fractionation of the leaf extract of C. laurifolia which is also the first phytochemical evaluation of this plant. Five flavonoids, namely quercetin (1, 6-methyl-7-methoxyapigenin (2, avicularin (3, quercitrin (4 and hyperoside (5, together with betulinic acid (6, were isolated from the leaf extract of C. laurifolia. All isolated compounds were tested individually against the DENV-NS5 RdRp and compared with four other commercial flavonoids: isoquercitrin (7, spiraeoside (8, quercetin-3,4’-di-O-glucoside (9 and rutine (10. Compounds 3, 4, 6, 8 and 10 displayed IC 50 ranging from 1.7 to 2.1 µM, and were the most active against the DENV-NS5 RdRp.

  13. Frequency of Natural Resistance within NS5a Replication Complex Domain in Hepatitis C Genotypes 1a, 1b: Possible Implication of Subtype-Specific Resistance Selection in Multiple Direct Acting Antivirals Drugs Combination Treatment

    Directory of Open Access Journals (Sweden)

    Sabrina Bagaglio

    2016-03-01

    Full Text Available Different HCV subtypes may naturally harbor different resistance selection to anti-NS5a inhibitors. 2761 sequences retrieved from the Los Alamos HCV database were analyzed in the NS5a domain 1, the target of NS5a inhibitors. The NS5a resistance-associated polymorphisms (RAPs were more frequently detected in HCV G1b compared to G1a. The prevalence of polymorphisms associated with cross-resistance to compounds in clinical use (daclatasvir, DCV, ledipasvir, LDV, ombitasvir, and OMV or scheduled to come into clinical use in the near future (IDX719, elbasvir, and ELV was higher in G1b compared to G1a (37/1552 (2.4% in 1b sequences and 15/1209 (1.2% in 1a isolates, p = 0.040. Interestingly, on the basis of the genotype-specific resistance pattern, 95 (6.1% G1b sequences had L31M RAP to DCV/IDX719, while 6 sequences of G1a (0.5% harbored L31M RAP, conferring resistance to DCV/LDV/IDX719/ELV (p < 0.0001. Finally, 28 (2.3% G1a and none of G1b isolates harbored M28V RAP to OMV (p < 0.0001. In conclusion, the pattern of subtype-specific resistance selection in the naturally occurring strains may guide the treatment option in association with direct acting antivirals (DAAs targeting different regions, particularly in patients that are difficult to cure, such as those with advanced liver disease or individuals who have failed previous DAAs.

  14. Early and reliable detection of herpes simplex virus type 1 and varicella zoster virus DNAs in oral fluid of patients with idiopathic peripheral facial nerve palsy: Decision support regarding antiviral treatment?

    Science.gov (United States)

    Lackner, Andreas; Kessler, Harald H; Walch, Christian; Quasthoff, Stefan; Raggam, Reinhard B

    2010-09-01

    Idiopathic peripheral facial nerve palsy has been associated with the reactivation of herpes simplex virus type 1 (HSV-1) or varicella zoster virus (VZV). In recent studies, detection rates were found to vary strongly which may be caused by the use of different oral fluid collection devices in combination with molecular assays lacking standardization. In this single-center pilot study, liquid phase-based and absorption-based oral fluid collection was compared. Samples were collected with both systems from 10 patients with acute idiopathic peripheral facial nerve palsy, 10 with herpes labialis or with Ramsay Hunt syndrome, and 10 healthy controls. Commercially available IVD/CE-labeled molecular assays based on fully automated DNA extraction and real-time PCR were employed. With the liquid phase-based oral fluid collection system, three patients with idiopathic peripheral facial nerve palsy tested positive for HSV-1 DNA and another two tested positive for VZV DNA. All patients with herpes labialis tested positive for HSV-1 DNA and all patients with Ramsay Hunt syndrome tested positive for VZV DNA. With the absorption-based oral fluid collection system, detections rates and viral loads were found to be significantly lower when compared to those obtained with the liquid phase-based collection system. Collection of oral fluid with a liquid phase-based system and the use of automated and standardized molecular methods allow early and reliable detection of HSV-1 and VZV DNAs in patients with acute idiopathic peripheral facial nerve palsy and may provide a valuable decision support regarding start of antiviral treatment at the first clinical visit.

  15. Non-lethal heat treatment of cells results in reduction of tumor initiation and metastatic potential

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Yoo-Shin; Lee, Tae Hoon; O' Neill, Brian E., E-mail: BEOneill@houstonmethodist.org

    2015-08-14

    Non-lethal hyperthermia is used clinically as adjuvant treatment to radiation, with mixed results. Denaturation of protein during hyperthermia treatment is expected to synergize with radiation damage to cause cell cycle arrest and apoptosis. Alternatively, hyperthermia is known to cause tissue level changes in blood flow, increasing the oxygenation and radiosensitivity of often hypoxic tumors. In this study, we elucidate a third possibility, that hyperthermia alters cellular adhesion and mechanotransduction, with particular impact on the cancer stem cell population. We demonstrate that cell heating results in a robust but temporary loss of cancer cell aggressiveness and metastatic potential in mouse models. In vitro, this heating results in a temporary loss in cell mobility, adhesion, and proliferation. Our hypothesis is that the loss of cellular adhesion results in suppression of cancer stem cells and loss of tumor virulence and metastatic potential. Our study suggests that the metastatic potential of cancer is particularly reduced by the effects of heat on cellular adhesion and mechanotransduction. If true, this could help explain both the successes and failures of clinical hyperthermia, and suggest ways to target treatments to those who would most benefit. - Highlights: • Non-lethal hyperthermia treatment of cancer cells is shown to cause a reduction in rates of tumor initiation and metastasis. • Dynamic imaging of cells during heat treatment shows temporary changes in cell shape, cell migration, and cell proliferation. • Loss of adhesion may lead to the observed effect, which may disproportionately impact the tumor initiating cell fraction. • Loss or suppression of the tumor initiating cell fraction results in the observed loss of metastatic potential in vivo. • This result may lead to new approaches to synergizing hyperthermia with surgery, radiation, and chemotherapy.

  16. RNAi:antiviral therapy against dengue virus

    Institute of Scientific and Technical Information of China (English)

    Sobia Idrees; Usman A Ashfaq

    2013-01-01

    Dengue virus infection has become a global threat affecting around 100 countries in the world. Currently, there is no licensed antiviral agent available against dengue. Thus, there is a strong need to develop therapeutic strategies that can tackle this life threatening disease. RNA interference is an important and effective gene silencing process which degrades targeted RNA by a sequence specific process. Several studies have been conducted during the last decade to evaluate the efficiency of siRNA in inhibiting dengue virus replication. This review summarizes siRNAs as a therapeutic approach against dengue virus serotypes and concludes that siRNAs against virus and host genes can be next generation treatment of dengue virus infection.

  17. Treatment with an orthopedic appliance system in relation to treatment intensity and growth periods. A study of initial effects.

    Science.gov (United States)

    Malmgren, O; Omblus, J; Hägg, U; Pancherz, H

    1987-02-01

    The study comprises an analysis of the effect of treatment with a modified activator combined with a high-pull headgear during a standardized observation period of the initial 6 months of treatment. All patients (24 girls and 32 boys, aged 8.5 to 15 years) had severe skeletal Class II malocclusion. In the first part of the study, the effect of treatment with the appliance both day and night is compared with the effect when it was worn only at night. Only a small and nonsignificant difference was found, but the patients tended to cooperate better if they were instructed to wear the appliance continuously. In the second part of the study, the effect of treatment is related to the somatic maturation of the patients. Longitudinal records of standing height were used to assess whether treatment had been performed before maximal pubertal growth (prepeak period), during maximal pubertal growth (peak period), or after maximal pubertal growth (postpeak period). The skeletal effect was significantly greater in boys treated during the peak period than in those treated during the prepeak period and a similar tendency, although not significant, was found among girls. The number of patients treated during the postpeak period was too small for statistical analysis.

  18. Correlates of Initiation of Treatment for Chronic Hepatitis C Infection in United States Veterans, 2004-2009.

    Directory of Open Access Journals (Sweden)

    Adi V Gundlapalli

    Full Text Available We describe the rates and predictors of initiation of treatment for chronic hepatitis C (HCV infection in a large cohort of HCV positive Veterans seen in U.S. Department of Veterans Affairs (VA facilities between January 1, 2004 and December 31, 2009. In addition, we identify the relationship between homelessness among these Veterans and treatment initiation. Univariate and multivariable Cox Proportional Hazards regression models with time-varying covariates were used to identify predictors of initiation of treatment with pegylated interferon alpha plus ribavirin. Of the 101,444 HCV treatment-naïve Veterans during the study period, rates of initiation of treatment among homeless and non-homeless Veterans with HCV were low and clinically similar (6.2% vs. 7.4%, p<0.0001. For all U.S. Veterans, being diagnosed with genotype 2 or 3, black or other/unknown race, having Medicare or other insurance increased the risk of treatment. Veterans with age ≥50 years, drug abuse, diabetes, and hemoglobin < 10 g/dL showed lower rates of treatment. Initiation of treatment for HCV in homeless Veterans is low; similar factors predicted initiation of treatment. Additionally, exposure to treatment with medications for diabetes predicted lower rates of treatment. As newer therapies become available for HCV, these results may inform further studies and guide strategies to increase treatment rates in all U.S. Veterans and those who experience homelessness.

  19. Guidelines for screening, prophylaxis and critical information prior to initiating anti-TNF-alpha treatment

    DEFF Research Database (Denmark)

    Lassen, Inge Nordgaard; Dahlerup, Jens Frederik; Belard, Erika

    2012-01-01

    These national clinical guidelines outlining the screening, prophylaxis and critical information required prior to initiating anti-TNF-alpha treatment have been approved by the Danish Society for Gastroenterology. Anti-TNF-alpha therapy is widely used in gastroenterology (for inflammatory bowel...... disease), rheumatology (for rheumatoid arthritis, psoriatic arthritis and spondyloarthropathies) and dermatology (for psoriasis). With this background, the Danish Society for Gastroenterology established a group of experts to assess evidence for actions recommended before treatment with anti...... a history of previous malignancies (cases of malignant disease within 5 years of anti-TNF-alpha treatment should be carefully considered). The physical examination should include lung/heart auscultation and lymph node examination, and the paraclinical investigations should include chest X...

  20. Guidelines for screening, prophylaxis and critical information prior to initiating anti-TNF-alpha treatment

    DEFF Research Database (Denmark)

    Nordgaard-Lassen, Inge; Dahlerup, Jens Frederik; Belard, Erika

    2012-01-01

    a history of previous malignancies (cases of malignant disease within 5 years of anti-TNF-alpha treatment should be carefully considered). The physical examination should include lung/heart auscultation and lymph node examination, and the paraclinical investigations should include chest X-rays......These national clinical guidelines outlining the screening, prophylaxis and critical information required prior to initiating anti-TNF-alpha treatment have been approved by the Danish Society for Gastroenterology. Anti-TNF-alpha therapy is widely used in gastroenterology (for inflammatory bowel...... disease), rheumatology (for rheumatoid arthritis, psoriatic arthritis and spondyloarthropathies) and dermatology (for psoriasis). With this background, the Danish Society for Gastroenterology established a group of experts to assess evidence for actions recommended before treatment with anti-TNF-alpha...

  1. First-year treatment costs among new initiators of topical prostaglandin analogs: pooled results

    Directory of Open Access Journals (Sweden)

    Jordana K Schmier

    2010-05-01

    Full Text Available Jordana K Schmier1, David W Covert21Managing Scientist, Exponent Inc., Alexandria, VA, USA; 2Associate Director, Health Economics, Alcon Research Ltd., Ft. Worth, TX, USAObjective: To estimate first-year treatment costs among new initiators of topical prostaglandin analogs in a managed care population.Research design and methods: A model was developed to estimate first-year medical costs. Model inputs were based on weighted results from three previous studies. Treatment patterns were derived from a claims database analysis. Published studies were used to estimate visit-related resource use. Costs were obtained from standard sources.Results: Across studies, 27,809 patients met study criteria, 44.2% of whom remained on their index therapy for 12 months. Adjunctive therapy was needed in 22.5%, 18.5%, and 11.9% of bimatoprost, latanoprost, and benzalkonium chloride (BAK-free travoprost patients, respectively. Median days to initiating adjunctive therapy were 64, 67, and 127 for bimatoprost, latanoprost, and BAK-free travoprost patients. Estimated first-year medical costs were $1,945, $1,803, and $1,730 for patients initiating therapy with bimatoprost, latanoprost, and BAK-free travoprost. Findings were consistent through sensitivity analysis.Conclusions: A BAK-free prostaglandin analog may permit longer duration of monotherapy and be associated with lower first-year treatment costs. Use of a claims database and the selection of new initiators of prostaglandin analogs limit the ability to project findings to all glaucoma patients.Keywords: costs and cost analysis, drug therapy, combination, glaucoma, prostaglandin analogs

  2. Treatment delay among tuberculosis patients in Tanzania: Data from the FIDELIS Initiative

    Directory of Open Access Journals (Sweden)

    Enarson Donald A

    2011-05-01

    Full Text Available Abstract Background Several FIDELIS projects (Fund for Innovative DOTS Expansion through Local Initiatives to Stop TB in Tanzania were conducted by the National Tuberculosis and Leprosy Programme (NTLP during the years 2004-2008 to strengthen diagnostic and treatment services. These projects collected information on treatment delay and some of it was available for research purposes. With this database our objective was to assess the duration and determinants of treatment delay among new smear positive pulmonary tuberculosis (TB patients in FIDELIS projects, and to compare delay according to provider visited prior to diagnosis. Methods Treatment delay among new smear positive TB patients was recorded for each patient at treatment initiation and this information was available and fairly complete in 6 out of 57 districts with FIDELIS projects enrolling patients between 2004 and 2007; other districts had discarded their forms at the time of analysis. It was analysed as a cross sectional study. Results We included 1161 cases, 10% of all patients recruited in the FIDELIS projects in Tanzania. Median delay was 12 weeks. The median duration of cough, weight loss and haemoptysis was 12, 8 and 3 weeks, respectively. Compared to Hai district Handeni had patients with longer delays and Mbozi had patients with shorter delays. Urban and rural patients reported similar delays. Patients aged 15-24 years and patients of 65 years or older had longer delays. Patients reporting contact with traditional healers before diagnosis had a median delay of 15 weeks compared to 12 weeks among those who did not. Patients with dyspnoea and with diarrhoea had longer delays. Conclusion In this patient sample in Tanzania half of the new smear positive pulmonary tuberculosis patients had a treatment delay longer than 12 weeks. Delay was similar in men and women and among urban and rural patients, but longer in the young and older age groups. Patients using traditional healers had

  3. Evaluation of antiseptic antiviral activity of chemical agents.

    Science.gov (United States)

    Geller, Chloé; Finance, Chantal; Duval, Raphaël Emmanuel

    2011-06-01

    Antiviral antisepsis and disinfection are crucial for preventing the environmental spread of viral infections. Emerging viruses and associated diseases, as well as nosocomial viral infections, have become a real issue in medical fields, and there are very few efficient and specific treatments available to fight most of these infections. Another issue is the potential environmental resistance and spread of viral particles. Therefore, it is essential to properly evaluate the efficacy of antiseptics-disinfectants (ATS-D) on viruses. ATS-D antiviral activity is evaluated by (1) combining viruses and test product for an appropriately defined and precise contact time, (2) neutralizing product activity, and (3) estimating the loss of viral infectivity. A germicide can be considered to have an efficient ATS-D antiviral activity if it induces a >3 or >4 log(10) reduction (American and European regulatory agency requirements, respectively) in viral titers in a defined contact time. This unit describes a global methodology for evaluating chemical ATS-D antiviral activity.

  4. First-year treatment costs among new initiators of topical prostaglandin analogs

    Directory of Open Access Journals (Sweden)

    Jordana K Schmier

    2009-11-01

    Full Text Available Jordana K Schmier1, David W Covert2, Alan L Robin3,41Exponent Inc., Alexandria, VA, USA; 2Health Economics, Alcon Research Ltd., Fort Worth, TX, USA; 3Department of Ophthalmology, University of Maryland, Baltimore, MD, USA; 4Wilmer Eye Institute, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USAObjective: To estimate first-year costs among new initiators of topical prostaglandin analogs in a managed care population.Research design and methods: We developed a model to estimate first-year direct medical costs. We derived treatment patterns from a claims database analysis. Published studies were used to estimate visit-related resource use. Costs were obtained from standard sources.Results: The database analysis identified 9,063 patients meeting study criteria, 41% (n = 3,672 of whom remained on their initial prostaglandin therapy for 12 months after initiation. Adjunctive intraocular pressure lowering therapy was needed in 20.7%, 16.5%, 13.9%, and 8.9% of bimatoprost, latanoprost, travoprost, and BAK-free travoprost patients, respectively. Median numbers of days to the first prescription filled for adjunctive therapy (if required were 69.5, 67.0, 123.0, and 158.5 for patients initiating on bimatoprost, latanoprost, travoprost, and BAK-free travoprost. Total estimated first-year costs were $1,457, $1,360, $1,278, and $1,307 for patients initiating therapy with bimatoprost, latanoprost, travoprost, and BAK-free travoprost. Findings were consistent through sensitivity analysis.Conclusions: A BAK-free prostaglandin analog may permit longer duration of monotherapy and be associated with lower first-year direct medical costs. Use of a claims database and the selection of new initiators of prostaglandin analogs limit projecting findings to all glaucoma patients.Keywords: costs and cost analysis, drug therapy, combination, glaucoma, prostaglandin analogs

  5. The Microcirculation Is Unchanged in Neonates with Severe Respiratory Failure after the Initiation of ECMO Treatment

    Directory of Open Access Journals (Sweden)

    Anke P. C. Top

    2012-01-01

    Full Text Available Purpose. Venoarterial extracorporeal membrane oxygenation (VA-ECMO is known to improve cardiorespiratory function and outcome in neonates with severe respiratory failure. We tested the hypothesis that VA-ECMO therapy improves the microcirculation in neonates with severe respiratory failure. Methods. This single-center prospective observational pilot study took place in an intensive care unit of a level III university children’s hospital. Twenty-one-term neonates, who received VA-ECMO treatment, were included. The microcirculation was assessed in the buccal mucosa, using Orthogonal Polarization Spectral imaging, within 24 hours before (T1 and within the first 24 hours after initiation of ECMO treatment (T2. Data were compared to data of a ventilated control group (=7. Results. At baseline (T1, median functional capillary density (FCD, microvascular flow index (MFI, and heterogeneity index (HI did not differ between the ECMO group and the control group. At T2 the median FCD was lower in the control group (median [range]: 2.4 [1.4–4.2] versus 4.3 [2.8–7.4] cm/cm2; P value <0.001. For MFI and HI there were no differences at T2 between the two groups. Conclusion. The perfusion of the microcirculation does not change after initiation of VA-ECMO treatment in neonates with severe respiratory failure.

  6. Epimedium koreanum Nakai Displays Broad Spectrum of Antiviral Activity in Vitro and in Vivo by Inducing Cellular Antiviral State

    Directory of Open Access Journals (Sweden)

    Won-Kyung Cho

    2015-01-01

    Full Text Available Epimedium koreanum Nakai has been extensively used in traditional Korean and Chinese medicine to treat a variety of diseases. Despite the plant’s known immune modulatory potential and chemical make-up, scientific information on its antiviral properties and mode of action have not been completely investigated. In this study, the broad antiviral spectrum and mode of action of an aqueous extract from Epimedium koreanum Nakai was evaluated in vitro, and moreover, the protective effect against divergent influenza A subtypes was determined in BALB/c mice. An effective dose of Epimedium koreanum Nakai markedly reduced the replication of Influenza A Virus (PR8, Vesicular Stomatitis Virus (VSV, Herpes Simplex Virus (HSV and Newcastle Disease Virus (NDV in RAW264.7 and HEK293T cells. Mechanically, we found that an aqueous extract from Epimedium koreanum Nakai induced the secretion of type I IFN and pro-inflammatory cytokines and the subsequent stimulation of the antiviral state in cells. Among various components present in the extract, quercetin was confirmed to have striking antiviral properties. The oral administration of Epimedium koreanum Nakai exhibited preventive effects on BALB/c mice against lethal doses of highly pathogenic influenza A subtypes (H1N1, H5N2, H7N3 and H9N2. Therefore, an extract of Epimedium koreanum Nakai and its components play roles as immunomodulators in the innate immune response, and may be potential candidates for prophylactic or therapeutic treatments against diverse viruses in animal and humans.

  7. POEMS Syndrome in a Juvenile Initially Diagnosed as Treatment Resistant Chronic Inflammatory Demyelinating Polyneuropathy.

    Science.gov (United States)

    Krish, Sonia N; Nguyen, Thy; Biliciler, Suur; Kumaravel, Manickam; Wahed, Amer; Risin, Semyon; Sheikh, Kazim A

    2015-12-01

    POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, skin changes) is a disorder that mainly affects adults. We report a pediatric patient, initially considered to have Guillain-Barré syndrome, who continued to have progression of neuropathic disease leading to the diagnosis of chronic inflammatory demyelinating polyneuropathy. Diagnosis of POEMS was established by an abnormal bone marrow biopsy, prompted by laboratory and imaging findings, which became abnormal later in the course of the disease. POEMS syndrome is extremely rare in children, and neuropathic features in this age group have not been previously described. This case illustrates that "Guillain-Barré syndrome-like" initial presentation for POEMS, which has not been previously reported. It also emphasizes that in children with progressive acquired neuropathies that are treatment unresponsive, POEMS syndrome should be considered.

  8. 78 FR 12759 - Draft Guidance for Industry on Attachment to Guidance on Antiviral Product Development-Conducting...

    Science.gov (United States)

    2013-02-25

    ... Antiviral Product Development--Conducting and Submitting Virology Studies to the Agency: Guidance for... guidance for industry entitled ``Attachment to Guidance on Antiviral Product Development--Conducting and... important for supporting clinical trials of products in development for the treatment of HCV. HCV...

  9. Broad-spectrum antiviral therapeutics.

    Directory of Open Access Journals (Sweden)

    Todd H Rider

    Full Text Available Currently there are relatively few antiviral therapeutics, and most which do exist are highly pathogen-specific or have other disadvantages. We have developed a new broad-spectrum antiviral approach, dubbed Double-stranded RNA (dsRNA Activated Caspase Oligomerizer (DRACO that selectively induces apoptosis in cells containing viral dsRNA, rapidly killing infected cells without harming uninfected cells. We have created DRACOs and shown that they are nontoxic in 11 mammalian cell types and effective against 15 different viruses, including dengue flavivirus, Amapari and Tacaribe arenaviruses, Guama bunyavirus, and H1N1 influenza. We have also demonstrated that DRACOs can rescue mice challenged with H1N1 influenza. DRACOs have the potential to be effective therapeutics or prophylactics for numerous clinical and priority viruses, due to the broad-spectrum sensitivity of the dsRNA detection domain, the potent activity of the apoptosis induction domain, and the novel direct linkage between the two which viruses have never encountered.

  10. [How to initiate, optimise and stop pharmacological treatments: applications in real life].

    Science.gov (United States)

    Scheen, A J

    2015-01-01

    Some patients are exposed to complex clinical situations, which impose a careful analysis of both the indications and contraindications of ongoing pharmacological treatments as well as of the dosing or drug adjustments to be proposed. This article illustrates some problems encountered when a new drug therapy is initiated, when medications with narrow therapeutic window should be supervised and when some drugs should be stopped mainly for safety reasons. The clinical case relates the story of a patient with type 2 diabetes, arterial hypertension and coronary heart disease, who presents a congestive heart failure associated with an episode of atrial fibrillation and a severe renal insufficiency.

  11. What You Should Know about Flu Antiviral Drugs

    Science.gov (United States)

    ... this? Submit What's this? Submit Button Past Newsletters What You Should Know About Flu Antiviral Drugs Language: ... that can be used to treat flu illness. What are antiviral drugs? Antiviral drugs are prescription medicines ( ...

  12. Antiviral Activity of Isatis indigotica Extract and Its Derived Indirubin against Japanese Encephalitis Virus

    Directory of Open Access Journals (Sweden)

    Shu-Jen Chang

    2012-01-01

    Full Text Available Isatis indigotica is widely used in Chinese Traditional Medicine for clinical treatment of virus infection, tumor, and inflammation, yet its antiviral activities remain unclear. This study probed antiviral activity of I. indigotica extract and its marker compounds against Japanese encephalitis virus (JEV. I. indigotica methanol extract, indigo, and indirubin proved less cytotoxic than other components, showing inhibitory effect (concentration-dependent on JEV replication in vitro. Time-of-addition experiments proved the extract, indigo, and indirubin with potent antiviral effect by pretreatment (before infection or simultaneous treatment (during infection, but not posttreatment (after entry. Antiviral action of these agents showed correlation with blocking virus attachment and exhibited potent virucidal activity. In particular, indirubin had strong protective ability in a mouse model with lethal JEV challenge. The study could yield anti-JEV agents.

  13. The Use of Antiviral Drugs for Influenza: Guidance for Practitioners 2012/2013

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    Fred Y Aoki

    2012-01-01

    Seasonal influenza in 2012/2013 is predicted to be caused by two human influenza A and one influenza B strain, all of which are anticipated to remain generally susceptible to oseltamivir.The predicted strains are A/California/7/2009 (H1N1 pdm09-like, A/Victoria/361/2011 (H3N2-like and B/Wisconsin/1/2010-like (Yamagata lineage. All are included in the seasonal influenza vaccine and are susceptible to oseltamivir.Swine-variant H3N2v, which has rarely caused infection in humans exposed to infected swine within the past year in the United States, is susceptible to oseltamivir. It is not included in the current seasonal influenza vaccine.It is still considered that initiation of antiviral therapy more than 36 h to 48 h after onset of symptoms is beneficial in patients hospitalized with complicated influenza and severe illness.Oseltamivir continues to be recommended for the treatment of influenza in pregnant women.The use of antiviral drugs among measures to control outbreaks of influenza in closed facilities such as correctional institutions is now included in the present document.

  14. Awareness of gastroenterologist in tertiary hospitals in Chengdu about guideline of antiviral treatment of patients with hepatitis B virus-induced liver cirrhosis%成都市三级医院消化专科医师关于乙型肝炎肝硬化患者抗病毒治疗专业知识知晓情况调查

    Institute of Scientific and Technical Information of China (English)

    张笛; 李良平

    2015-01-01

    Objective To investigate the awareness of antiviral treatment in patients with hepatitis B virus (HBV)-related liver cirrhosis and the content of chronic hepatitis B prevention and treatment guidelines(2010, China)in gastroenterologist from tertiary hospitals in Chengdu. Methods Questionnaire based on newly published chronic hepatitis B prevention and treatment guidelines were designed and a total of 224 gastroenterologists in 20 tertiary general hospitals in Chengdu completed the questionnaires on the principle of volunteer,anonymity and in-dependence. The questionnaires were collected by special investigators from our team. Results 208 (92.9%) re-spondents acquired the treatment-related acknowledge mainly by reading the updated guidelines. The necessity and course of anti-HBV regimen were well known,with 220 respondents(98.2%) knowing the antiviral treatment neces-sary to patients with HBV-related cirrhosis,but 203 (90.63%) unaware of the course of treatment. However,the re-spondents were relatively poor understanding of the antiviral indications,treatment process and follow-up. Only 40 (17.9%) respondents gave the correct answer of antiviral indications in HBeAg-positive patients in compensated stage;35(15.6%) gave the correct answer of antiviral indications in HBeAg-negative patients in compensated stage;87 (38.8%) gave the correct answer of antiviral indications in patients with decompensated HBV-related cirrhosis;only 28 (12.5%) knew the requirement of follow-up in patients with stable condition after treatment. Ac-cording to the survey of this study,adefovir dipivoxil, one of nucleoside analogues,was best known,by 193 (86.2%) respondents,and 161 (71.9%) respondentsbelieved that the costs of the medicine was the major factor determining the choice of antiviral medication. Con-clusion Gastroenterologists in tertiary general hospitals in Chengdu have a good understanding of the purpose and necessity of antiviral treatment in patients with HBV-related liver

  15. Optimization of Influenza Antiviral Response in Texas

    Science.gov (United States)

    2015-03-01

    the population-proportionate antiviral release schedule worked comparably the xvi TAVRS antiviral release schedule. However, in response to a...12/1/05- 1254_article Lee, N., Chan, P. K., Choi, K. W., Lui , G., Wong, B., Cockram, C. S. …Sung, J.J. (2007). Factors associated with early

  16. Pubertal development among girls with classical congenital adrenal hyperplasia initiated on treatment at different ages

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    Bindu Kulshreshtha

    2012-01-01

    Full Text Available Introduction: Children with congenital adrenal hyperplasia (CAH provide us an opportunity to study the clinical effects of androgen excess in humans. We studied the sequence of pubertal development in girls with congenital adrenal hyperplasia initiated on treatment at different ages, to assess the effects of androgen exposure on the Hypothalamic-Pituitary-Ovarian (HPO axis. Materials and Methods: Girls more than 18 years of age, with CAH, on follow-up at this hospital were the subjects for this study. Details of history, physical findings, laboratory evaluation, and medication were noted from their case records and verified from the patients and their / parents, in addition to assessment of their present health status. Result: We studied 24 patients of classical CAH (SW-2, SV-22, average age - 24.5 ± 6.6 years. All had varying degrees of genital ambiguity (Prader stage 3 (n = 13, Prader stage 2 (n = 10, Prader stage 1 (n = 1. Among them were13 girls, who were started on steroids after eight years of age. Girls who received treatment from infancy and early childhood had normal pubertal development (mean age at menarche 11.4 ± 1.7 years. Hirsutism was not a problem among them. Untreated children had progressive clitoral enlargement throughout childhood, developed pubic hair at around three to six years of age, and facial hair between nine and eleven years. Plasma testosterone ranged from 3 to 6 ng / ml prior to treatment. Six of the 13 untreated CAH girls had subtle breast development starting at ages 11 - 16 years and three had spontaneous infrequent vaginal bleeding starting at ages 11 - 17. Steroid supplementation initiated pubertal changes in older girls in two-to-six months′ time. Conclusion: There was a delay in HPO axis maturation (as evidenced by delayed pubertal development in the absence of treatment in girls with CAH. This could be corrected with steroid supplementation.

  17. Antiviral activity of ovotransferrin derived peptides.

    Science.gov (United States)

    Giansanti, Francesco; Massucci, M Teresa; Giardi, M Federica; Nozza, Fabrizio; Pulsinelli, Emy; Nicolini, Claudio; Botti, Dario; Antonini, Giovanni

    2005-05-27

    Ovotransferrin and lactoferrin are iron-binding proteins with antiviral and antibacterial activities related to natural immunity, showing marked sequence and structural homologies. The antiviral activity of two hen ovotransferrin fragments DQKDEYELL (hOtrf(219-227)) and KDLLFK (hOtrf(269-301) and hOtrf(633-638)) towards Marek's disease virus infection of chicken embryo fibroblasts is reported here. These fragments have sequence homology with two bovine lactoferrin fragments with antiviral activity towards herpes simplex virus, suggesting that these fragments could have a role for the exploitation of the antiviral activity of the intact proteins towards herpes viruses. NMR analysis showed that these peptides, chemically synthetized, did not possess any favourite conformation in solution, indicating that both the aminoacid sequence and the conformation they display in the intact protein are essential for the antiviral activity.

  18. Undesirable financial effects of head and neck cancer radiotherapy during the initial treatment period

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    Helen Egestad

    2015-01-01

    Full Text Available Background: Healthcare cost and reforms are at the forefront of international debates. One of the current discussion themes in oncology is whether and how patients’ life changes due to costs of cancer care. In Norway, the main part of the treatment costs is supported by general taxpayer revenues. Objectives: The objective of this study was to clarify whether head and neck cancer patients (n=67 in northern Norway experienced financial health-related quality of life (HRQOL deterioration due to costs associated with treatment. Design: HRQOL was examined by the European Organization for Research and Treatment of Cancer (EORTC QLQ-C30 in the beginning and in the end of radiation treatment in patients treated at the University Hospital in Northern Norway. Changes in financial HRQOL were calculated and compared by paired sample T-tests. Multiple regression analyses were used to examine correlations among gender, marital status, age and treatment with or without additional chemotherapy and changes in the HRQOL domain of financial difficulties. Results: The majority of score results at both time points were in the lower range (mean 15–25, indicating limited financial difficulties. We observed no statistically significant differences by gender, marital status and age. Increasing financial difficulties during treatment were reported by male patients and those younger than 65, that is, patients who were younger than retirement age. The largest effect was seen in singles. However, differences were not statistically significant. Conclusions: During the initial phase of the disease trajectory, no significant increase in financial difficulties was found. This is in line with the aims of the Norwegian public healthcare model. However, long-term longitudinal studies should be performed, especially with regard to the trends we observed in single, male and younger patients.

  19. Spinal epidural neurostimulation for treatment of acute and chronic intractable pain: initial and long term results.

    Science.gov (United States)

    Richardson, R R; Siqueira, E B; Cerullo, L J

    1979-09-01

    Spinal epidural neurostimulation, which evolved from dorsal column stimulation, has been found to be effective in the treatment of acute and chronic intractable pain. Urban and Hashold have shown that it is a safe, simplified alternative to dorsal column stimulation, especially because laminectomy is not required if the electrodes are inserted percutaneously. Percutaneous epidural neurostimulation is also advantageous because there can be a diagnostic trial period before permanent internalization and implantation. This diagnostic and therapeutic modality has been used in 36 patients during the past 3 years at Northwestern Memorial Hospital. Eleven of these patients had acute intractable pain, which was defined as pain of less than 1 year in duration. Initial postimplantation results from the 36 patients indicate that spinal epidural neurostimulation is most effective in treating the intractable pain of diabetes, arachnoiditis, and post-traumatic and postamputation neuroma. Long term follow-up, varying from 1 year to 3 years postimplantation in the 20 initially responding patients, indicates that the neurostimulation continues to provide significant pain relief (50% or greater) in a majority of the patients who experienced initial significant pain relief.

  20. The potential of antiviral agents to control classical swine fever: a modelling study.

    Science.gov (United States)

    Backer, Jantien A; Vrancken, Robert; Neyts, Johan; Goris, Nesya

    2013-09-01

    Classical swine fever (CSF) represents a continuous threat to pig populations that are free of disease without vaccination. When CSF virus is introduced, the minimal control strategy imposed by the EU is often insufficient to mitigate the epidemic. Additional measures such as preemptive culling encounter ethical objections, whereas emergency vaccination leads to prolonged export restrictions. Antiviral agents, however, provide instantaneous protection without inducing an antibody response. The use of antiviral agents to contain CSF epidemics is studied with a model describing within- and between-herd virus transmission. Epidemics are simulated in a densely populated livestock area in The Netherlands, with farms of varying sizes and pig types (finishers, piglets and sows). Our results show that vaccination and/or antiviral treatment in a 2 km radius around an infected herd is more effective than preemptive culling in a 1 km radius. However, the instantaneous but temporary protection provided by antiviral treatment is slightly less effective than the delayed but long-lasting protection offered by vaccination. Therefore, the most effective control strategy is to vaccinate animals when allowed (finishers and piglets) and to treat with antiviral agents when vaccination is prohibited (sows). As independent control measure, antiviral treatment in a 1 km radius presents an elevated risk of epidemics running out of control. A 2 km control radius largely eliminates this risk.

  1. Revisión sistemática de evaluaciones económicas de fármacos antivirales para el tratamiento de la hepatitis B crónica Economic evaluation of antiviral treatment for chronic hepatitis B: a systematic review

    Directory of Open Access Journals (Sweden)

    Lely Solari

    2010-03-01

    Full Text Available Objetivo. Revisar la evidencia disponible acerca de la costo-efectividad de los regímenes antivirales en el tratamiento de la hepatitis B crónica. Material y Métodos. Se realizó una revisión sistemática de las bases de datos de MEDLINE, LILACS, NICE guidelines y COCHRANE sobre evaluaciones económicas de regímenes antivirales para el tratamiento de hepatitis B crónica. Se incluyó los estudios originales, revisiones sistemáticas y guías de manejo conteniendo información acerca de la costo-efectividad de dicho tratamiento. Se registró las características y resultados de los documentos obtenidos. Resultados. Se obtuvo 29 artículos originales, cuatro artículos de revisión y cuatro guías de manejo clínico. La mayoría de las publicaciones fueron hechas en los cinco últimos años. Los autores tenían conflicto de interés, por trabajar en la industria farmacéutica, en 73% de los artículos originales. El 93% de los artículos que evalúan costo-efectividad de brindar tratamiento para hepatitis B crónica frente a manejo de complicaciones, encuentran que es costo-efectivo el tratamiento antiviral; 3/6 estudios que evalúan lamivudina frente a otros esquemas la encuentran como estrategia dominante, 3/5 encuentran a entecavir como estrategia dominante, 1/1 a tenofovir como dominante, 1/4 a interferón convencional como dominante y ninguno encuentra a adefovir ni interferón pegilado como estrategia dominante. Conclusiones. Consideramos que la evidencia disponible sugiere que brindar tratamiento antiviral para hepatitis B crónica sea una intervención costo-efectiva para muchos sistemas de salud, incluyendo el nuestro, con índices variables de costo-efectividad de acuerdo con los esquemas evaluados. Idealmente, se debe realizar evaluaciones económicas locales en este aspecto.Objective. To revise the available evidence on the cost-effectiveness of antiviral regimens for treatment of chronic hepatitis B. Material and methods. We

  2. Antiviral active peptide from oyster

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    An active peptide against herpes virus was isolated from the enzymic hydrolysate of oyster (Crassostrea gigas) and purified with the definite direction hydrolysis technique in the order of alcalase and bromelin. The hydrolysate was fractioned into four ranges of molecular weight (>10 kDa, 10-5 kDa, 5-1 kDa and <1 kDa) using ultrafiltration membranes and dialysis. The fraction of 10?5 kDa was purified using consecutive chromatographic methods including DEAE Sephadex A-25 column, Sephadex G-25 column, and high performance liquid chromatogram (HPLC) by activity-guided isolation. The antiviral effect of the obtained peptide on herpetic virus was investigated in Vero cells by observing cytopathic effect (CPE). The result shows that the peptide has high inhibitory activity on herpetic virus.

  3. Wide local excision could be considered as the initial treatment of primary anorectal malignant melanoma

    Institute of Scientific and Technical Information of China (English)

    ZHOU Hai-tao; ZHOU Zhi-xiang; ZHANG Hai-zeng; BI Jian-jun; ZHAO Ping

    2010-01-01

    Background Anorectal malignant melanoma was a rare disease with extremely poor prognosis. The aim of this study was to explore the clinical characteristic, diagnosis and treatment strategies of anorectal malignant melanoma. Methods The data of 57 patients with anorectal malignant melanoma was collected and retrospectively analyzed. Results Rectal bleeding and anal mass were found to be common symptoms of anorectal malignant melanoma. The preoperative diagnosis rate of anorectal malignant melanoma was 48.6%. The overall 3-year and 5-year survival rate was 38.0% and 21.3% respectively. The 3-year survival rates of stage I and II patients were 63.0% and 16.7% respectively (P=0.000), and the 5-year survival rates were 33.3% and 11.1% (P=0.001), which both had significant statistic differences. The 3-year survival rate of patients undergone abdmoninoperineal resection and patients undergone wide local excision were 36.7% and 53.0% respectively (P=0.280), while the 5-year survival rate were 24.1% and 23.1% (P=0.642), which both had no significant statistic differences. Conclusions This study identified no survival advantage to abdominoperineal resection in treatment of anorectal malignant melanoma, and we propose that wide local excision could be considered as the initial treatment of choice.

  4. Low Osteoporosis Treatment Initiation Rate in Women after Distal Forearm or Proximal Humerus Fracture: A Healthcare Database Nested Cohort Study.

    Directory of Open Access Journals (Sweden)

    Marie Viprey

    Full Text Available Treatment initiation rates following fragility fractures have often been reported to be low and in recent years numerous programs have been implemented worldwide to increase them. This study aimed at describing osteoporosis (OP treatment initiation in a representative sample of women who were hospitalized for a distal forearm fracture (DFF or proximal humerus fracture (PHF in 2009-2011 in France. The data source was a nationwide sample of 600,000 individuals, extracted from the French National Insurance Healthcare System database. All women aged 50 years and older who were hospitalized for a DFF or PHF between 2009 and 2011 and who had not received any OP treatment in the preceding 12 months were included in a retrospective cohort study. OP treatments initiated during the year following the fracture were analyzed. From 2009 to 2011, 729 women were hospitalized for a DFF or a PHF and 284 were on OP treatment at the time of the fracture occurrence. Among the 445 women who had no prevalent OP treatment, 131 (29.4% received supplementation treatment only (vitamin D and/or calcium and 42 (9.4% received a pharmacologic OP treatment in the year following their fracture. Pharmacological OP treatments included bisphosphonates (n = 21, strontium ranelate (n = 14, hormone replacement therapy (n = 4, or raloxifene (n = 3. General practitioners prescribed 75% of initial OP treatments. Despite the guidelines published in 2006 and the numerous initiatives to promote post-fracture OP treatment, OP treatment initiation rate in women who were hospitalized for a fragility fracture remained low in 2009-2011 in France.

  5. Antiviral Effect of Matrine against Human Enterovirus 71

    Directory of Open Access Journals (Sweden)

    Jiangning Liu

    2012-08-01

    Full Text Available Human enterovirus 71, a member of the Picornaviridae family, is one of the major causative agent of hand, foot and mouth disease in children less than six years old. This illness has caused mortalities in large-scale outbreaks in the Asia-Pacific region in recent years. No vaccine or antiviral therapy is available. In this study, antiviral effect of matrine against enterovirus 71 were evaluated in vitro and in vivo. Matrine could suppress the viral RNA copy number on rhabdomyosarcoma cells. Moreover, matrine treatment of mice challenged with a lethal dose of enterovirus 71 reduced the mortality and relieved clinical symptoms. The results showed that matrine may represent a potential therapeutic agent for enterovirus 71 infection.

  6. Photo-distributed lichenoid eruption secondary to direct anti-viral therapy for hepatitis C.

    Science.gov (United States)

    Simpson, Cory L; McCausland, Drew; Chu, Emily Y

    2015-10-01

    Novel direct anti-viral agents are emerging as effective treatments for hepatitis C virus (HCV) and provide an alternative to the year-long standard therapy with interferon and ribavirin. However, cutaneous side effects from these new medications, including rash, pruritus and photosensitivity, are among the most commonly reported adverse events and have resulted in therapy discontinuation in some cases. Here, we report two cases of a photo-distributed lichenoid eruption that occurred within 1  month of starting anti-viral therapy with simeprevir and sofosbuvir without interferon or ribavirin. This report provides the first histologic description of the cutaneous eruption associated with direct anti-viral therapy for HCV and highlights the importance of recognizing and treating the often intolerable dermatologic side effects of these novel medications, the incidence of which is likely to increase as direct anti-viral agents may become the standard of care for HCV.

  7. Physical activity and capacity at initiation of antiretroviral treatment in HIV patients in Ethiopia

    DEFF Research Database (Denmark)

    Olsen, Mette Frahm; Kæstel, Pernille; Tesfaye, M

    2015-01-01

    SUMMARY We described levels of habitual physical activity and physical capacity in HIV patients initiating antiretroviral treatment in Ethiopia and assessed the role of HIV and nutritional indicators on these outcomes. Physical activity energy expenditure (PAEE) and activity levels were measured...... with combined heart rate and movement sensors. Physical capacity was assessed by grip strength, sleeping heart rate and heart rate economy. Grip strength data was also available from a sex- and age-matched HIV-negative reference group. Median PAEE was 27·9 (interquartile range 17·4-39·8) kJ/kg per day and mean......±s.d. grip strength was 23·6 ± 6·7 kg. Advanced HIV disease predicted reduced levels of both physical activity and capacity; e.g. each unit viral load [log(1+copies/ml)] was associated with -15% PAEE (P

  8. The pivotal role of the intermediate fragment in initial operative treatment of olecranon fractures

    Directory of Open Access Journals (Sweden)

    Hierholzer Christian

    2011-02-01

    Full Text Available Abstract Background In order to improve initial operative treatment of complex olecranon fractures we searched for new determining details. We assumed that the intermediate fragment plays a decisive role for anatomic restoration of the trochlear notch and consecutive outcome of initial operative treatment. Methods 80 patients operated with diagnosis of complex olecranon fracture were identified in an 8-year-period from trauma unit files at two European Level 1 Trauma Centers. Retrospective review of all operative reports and radiographs/computer-tomography scans identified patients with concomitance of an intermediate fragment. The Patient-Rated Elbow Evaluation Score was calculated for 45 of 80 patients at a minimum of 8 months postoperatively (range 8-84 months. Results 29 patients were treated with stable internal fixation with figure-of-eight tension band wire fixation and 51 patients with posterior plate osteosynthesis with/without intramedullary screw. An intermediate fragment was seen in 52 patients. In 29 of these 52 patients, the intermediate fragment was described in operative report. 24 of these 29 patients were treated with posterior plate osteosynthesis, and 5 patients with figure-of-eight tension band wiring. Complications included superficial infection (2 patients, secondary dislocation (3 patients and heterotopic ossifications (1 patient. Functional outcome demonstrated a total PREE score of 9 points on average in 45 of 80 patients. Conclusion An extraordinary amount of patients showed an intermediate fragment. Consideration, desimpaction and anatomic reduction of the intermediate fragment are necessary preconditions for anatomic restoration of the trochlear notch. There is no clear benefit for plating versus tension band wiring according to our data. In the operative report precise description of the fracture pattern including presence of an intermediate fragment is recommended.

  9. The antiviral response to gamma interferon.

    Science.gov (United States)

    Costa-Pereira, Ana P; Williams, Timothy M; Strobl, Birgit; Watling, Diane; Briscoe, James; Kerr, Ian M

    2002-09-01

    A role for alpha/beta interferon (IFN-alpha/beta) in the IFN-gamma antiviral response has long been suggested. Accordingly, possible roles for autocrine or double-stranded-RNA (dsRNA)-induced IFN-alpha/beta in the IFN-gamma response were investigated. Use was made of wild-type and a variety of mutant human fibrosarcoma cell lines, including mutant U5A cells, which lack a functional IFN-alpha/beta receptor and hence an IFN-alpha/beta response. IFN-gamma did not induce detectable levels of IFN-alpha/beta in any of the cell lines, nor was the IFN-gamma response per se dependent on autocrine IFN-alpha/beta. On the other hand, a number of responses to dsRNA [poly(I). poly(C)] and encephalomyocarditis virus were greatly enhanced by IFN-gamma pretreatment (priming) of wild-type cells or of mutant cells lacking an IFN-alpha/beta response; these include the primary induction of dsRNA-inducible mRNAs, including IFN-beta mRNA, and, to a lesser extent, the dsRNA-mediated activation of the p38 mitogen-activated protein (MAP) kinase(s). IFN-gamma priming of mRNA induction by dsRNA is dependent on JAK1 and shows biphasic kinetics, with an initial rapid (<30-min) response being followed by a more substantial effect on overnight incubation. The IFN-gamma-primed dsRNA responses appear to be subject to modulation through the p38, phosphatidylinositol 3-kinase, and ERK1/ERK2 MAP kinase pathways. It can be concluded that despite efficient priming of IFN-beta production, the IFN-alpha/beta pathways play no significant role in the primary IFN-gamma antiviral response in these cell-virus systems. The observed IFN-gamma priming of dsRNA responses, on the other hand, will likely play a significant role in combating virus infection in vivo.

  10. Future of external beam irradiation as initial treatment of rectal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Papillon, J.

    1987-06-01

    The authors' protocol consists of a split-course regimen with a short course of cobalt-60 arc rotation (3000 c/Gy in 12 days). After 2 months rest, the second stage treatment depends upon the pressure of residual disease and the tumour site. It consists of either radical surgery (82 cases) or conservative treatment by intracavitary irradiation in the event of a favourable initial response or in the case of poor risk patients (73 cases). In the radiotherapy-surgical group, the subsequent operative specimens were tumour free in 17% of cases and assigned to Dukes' A category in 32% of cases. Of 91 patients with T/sub 2/ or T/sub 3/ tumour involving the lower third of the rectum (followed up for more than 3 years) 72(84%) had no recurrence. Thirty-three of these patients (46%) underwent a colostomy while 39 (54%) has normal anal function. These results demonstrate the major place that a properly planned external beam irradiation can have in the curative management of cancers of the low rectum.

  11. Quality assurance in the treatment of colorectal cancer: the EURECCA initiative.

    Science.gov (United States)

    Breugom, A J; Boelens, P G; van den Broek, C B M; Cervantes, A; Van Cutsem, E; Schmoll, H J; Valentini, V; van de Velde, C J H

    2014-08-01

    Colorectal cancer is one of the most common cancers in Europe. Over the past few decades, important advances have been made in screening, staging and treatment of colorectal cancer. However, considerable variation between and within European countries remains, which implies that further improvements are possible. The most important remaining question now is: when are we, health care professionals, delivering the best available care to patients with colon or rectal cancer? Currently, quality assurance is a major issue in colorectal cancer care and quality assurance awareness is developing in almost all disciplines involved in the treatment of colorectal cancer patients. Quality assurance has shown to be effective in clinical trials. For example, standardisation and quality control were introduced in the Dutch TME trial and led to marked improvements of local control and survival in rectal cancer patients. Besides, audit structures can also be very effective in monitoring cancer management and national audits showed to further improve outcome in colorectal cancer patients. To reduce the differences between European countries, an international, multidisciplinary, outcome-based quality improvement programme, European Registration of Cancer Care (EURECCA), has been initiated. In the near future, the EURECCA dataset will perform research on subgroups as elderly patients or patients with comorbidities, which are often excluded from trials. For optimal colorectal cancer care, quality assurance in guideline formation and in multidisciplinary team management is also of great importance. The aim of this review was to create greater awareness and to give an overview of quality assurance in the management of colorectal cancer.

  12. Decitabine Treatment of Glioma-Initiating Cells Enhances Immune Recognition and Killing

    Science.gov (United States)

    Riccadonna, Cristina; Yacoub Maroun, Céline; Vuillefroy de Silly, Romain; Boehler, Margaux; Calvo Tardón, Marta; Jueliger, Simone; Taverna, Pietro; Barba, Leticia; Marinari, Eliana; Pellegatta, Serena; Bassoy, Esen Yonca; Martinvalet, Denis; Dietrich, Pierre-Yves; Walker, Paul R.

    2016-01-01

    Malignant gliomas are aggressive brain tumours with very poor prognosis. The majority of glioma cells are differentiated (glioma-differentiated cells: GDCs), whereas the smaller population (glioma-initiating cells, GICs) is undifferentiated and resistant to conventional therapies. Therefore, to better target this pool of heterogeneous cells, a combination of diverse therapeutic approaches is envisaged. Here we investigated whether the immunosensitising properties of the hypomethylating agent decitabine can be extended to GICs. Using the murine GL261 cell line, we demonstrate that decitabine augments the expression of the death receptor FAS both on GDCs and GICs. Interestingly, it had a higher impact on GICs and correlated with an enhanced sensitivity to FASL-mediated cell death. Moreover, the expression of other critical molecules involved in cognate recognition by cytotoxic T lymphocytes, MHCI and ICAM-1, was upregulated by decitabine treatment. Consequently, T-cell mediated killing of both GDCs and GICs was enhanced, as was T cell proliferation after reactivation. Overall, although GICs are described to resist classical therapies, our study shows that hypomethylating agents have the potential to enhance glioma cell recognition and subsequent destruction by immune cells, regardless of their differentiation status. These results support the development of combinatorial treatment modalities including epigenetic modulation together with immunotherapy in order to treat heterogenous malignancies such as glioblastoma. PMID:27579489

  13. Efficacy and safety of glimepiride as initial treatment in Russian patients with type 2 diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Alexandr Sergeevich Ametov

    2013-12-01

    Full Text Available Aim. To investigate the efficacy and safety of glimepiride as initial mono-therapy in type 2 diabetes patients (T2DM.Materials and Methods. This is a multi-center, open-label prospective observational study. 245 treatment-naïve T2DM patients, who had not achieved glycemic goals on lifestyle therapy during first 12 weeks after the diagnosis, were enrolled in this study. Anti-diabetes treatment was initiated with glimepiride and continued during the 6-month follow-up period. Prescription of the initial dose (1 mg per day and further dose adjustments were carried out by the attending physician in accordance with the glimepiride data sheet. Dynamics of HbA1c, fasting plasma glucose (FPG, 2 h postprandial blood glucose (2hPPG, weight and waist circumference, as well as the incidence of hypoglycemia were the evaluated parameters.Results. The baseline HbA1c (mean: 7.9±0.5%; female: 7.8±0.4% ; male: 8.0±0.6% was significantly reduced at week 12 (mean 7.2±0.6%, p<0.001; female: 7.1±0.5%; male: 7.2±0.6%, and at the final visit (6.6±0.7%, p<0.001; female: 6.6±0.7; male: 6.5±0.7. 71.7% of the subjects achieved the HbA1c target (<7% at the end of the study. FPG and 2hPPG levels decreased by 2.3±1.3 mmol/L and 3.1±1.9 mmol/L, respectively (p<0.001. Of note, FPG and PPG at baseline were 8.2±1.2 mmol/L and 10.5±1.9 mmol/L, respectively. The incidence of hypoglycemia (as defined by BG ≤3.9 mmol/L in the presence of the relevant symptoms was 10.2%. Nocturnal symptomatic hypoglycemia was observed in 1.6% of cases. No severe hypoglycemic events were reported.Body weight and BMI reduced by 1.0 kg and 0.4 kg/m2, respectively, during the follow-up period. The mean glimepiride daily dose at the end of the follow-up was 2.8±1.3 mg. Observed reduction in weight and low incidence of hypoglycemia could be attributed to continued effects of the lifestyle therapy and relatively short history of T2DM (average duration of diabetes was 1.4±2.4 years

  14. CHOICE OF THE INITIAL TREATMENT FOR MILD TO MODERATE ARTERIAL HYPERTENSION IN MOSCOW PRIMARY PRACTICE

    Directory of Open Access Journals (Sweden)

    S. V. Gatsura

    2015-09-01

    Full Text Available Aim. To assess the choice of initial pharmacotherapy of uncomplicated mild to moderate arterial hypertension (HT in Moscow primary care as well as to clear up the influence of regulatory measures on this choice.Material and methods. Results of two similar surveys conducted in 2011-2012 (452 respondents and 2013-2014 (273 respondents were compared to estimate preferences of Moscow primary care physicians regarding initial antihypertensive agents for therapy of uncomplicated mild to moderate HT taking into consideration an influence of regulatory requirement to prescribe medicinal products by international nonproprietary name (INN since July 2012. All participants were proposed to write down their preferred antihypertensive agents for initial mono- or combined therapy of mild to moderate HT with moderate cardiovascular risk and absence of compelling indications.Results. Angiotensin converting enzyme inhibitors (ACEI remained the leading class of antihypertensive agents, though their popularity slightly but significantly declined from 44.4% in 2011-12 to 37.2% in 2013-14 (р<0.05. Angiotensin receptor blockers partially displaced the leaders and increased their popularity from 11.3% in 2011-12 to 18.0% in 2013-14 (р<0.01. ACEI/diuretic combination remained on the 3rd position (16.4% and 15.3% respectively. Beta-blockers and diuretics as monotherapy shared 4th and 5th places in this rating. Calcium channel blockers popularity among Moscow prescribers remained unchanged and poor – 2.1%. The most popular medicine by trade name was Noliprel, perindopril/indapamide fixed combination, – 14.0% and 13.7% of respondents in 2011-12 and 2013-14, respectively. The share of medicine products recommended by INN went up from 11.9% to 22.8% among top-10 popular medications (р<0.01.Conclusion. Blockers of renin-angiotensin-aldosterone system remain the leading drugs for the initial treatment of uncomplicated mild to moderate HT without compelling indications

  15. CHOICE OF THE INITIAL TREATMENT FOR MILD TO MODERATE ARTERIAL HYPERTENSION IN MOSCOW PRIMARY PRACTICE

    Directory of Open Access Journals (Sweden)

    S. V. Gatsura

    2014-01-01

    Full Text Available Aim. To assess the choice of initial pharmacotherapy of uncomplicated mild to moderate arterial hypertension (HT in Moscow primary care as well as to clear up the influence of regulatory measures on this choice.Material and methods. Results of two similar surveys conducted in 2011-2012 (452 respondents and 2013-2014 (273 respondents were compared to estimate preferences of Moscow primary care physicians regarding initial antihypertensive agents for therapy of uncomplicated mild to moderate HT taking into consideration an influence of regulatory requirement to prescribe medicinal products by international nonproprietary name (INN since July 2012. All participants were proposed to write down their preferred antihypertensive agents for initial mono- or combined therapy of mild to moderate HT with moderate cardiovascular risk and absence of compelling indications.Results. Angiotensin converting enzyme inhibitors (ACEI remained the leading class of antihypertensive agents, though their popularity slightly but significantly declined from 44.4% in 2011-12 to 37.2% in 2013-14 (р<0.05. Angiotensin receptor blockers partially displaced the leaders and increased their popularity from 11.3% in 2011-12 to 18.0% in 2013-14 (р<0.01. ACEI/diuretic combination remained on the 3rd position (16.4% and 15.3% respectively. Beta-blockers and diuretics as monotherapy shared 4th and 5th places in this rating. Calcium channel blockers popularity among Moscow prescribers remained unchanged and poor – 2.1%. The most popular medicine by trade name was Noliprel, perindopril/indapamide fixed combination, – 14.0% and 13.7% of respondents in 2011-12 and 2013-14, respectively. The share of medicine products recommended by INN went up from 11.9% to 22.8% among top-10 popular medications (р<0.01.Conclusion. Blockers of renin-angiotensin-aldosterone system remain the leading drugs for the initial treatment of uncomplicated mild to moderate HT without compelling indications

  16. Human influenza is more effective than avian influenza at antiviral suppression in airway cells.

    Science.gov (United States)

    Hsu, Alan Chen-Yu; Barr, Ian; Hansbro, Philip M; Wark, Peter A

    2011-06-01

    Airway epithelial cells are the initial site of infection with influenza viruses. The innate immune responses of airway epithelial cells to infection are important in limiting virus replication and spread. However, relatively little is known about the importance of this innate antiviral response to infection. Avian influenza viruses are a potential source of future pandemics; therefore, it is critical to examine the effectiveness of the host antiviral system to different influenza viruses. We used a human influenza (H3N2) and a low-pathogenic avian influenza (H11N9) to assess and compare the antiviral responses of Calu-3 cells. After infection, H3N2 replicated more effectively than the H11N9 in Calu-3 cells. This was not due to differential expression of sialic acid residues on Calu-3 cells, but was attributed to the interference of host antiviral responses by H3N2. H3N2 induced a delayed antiviral signaling and impaired type I and type III IFN induction compared with the H11N9. The gene encoding for nonstructural (NS) 1 protein was transfected into the bronchial epithelial cells (BECs), and the H3N2 NS1 induced a greater inhibition of antiviral responses compared with the H11N9 NS1. Although the low-pathogenic avian influenza virus was capable of infecting BECs, the human influenza virus replicated more effectively than avian influenza virus in BECs, and this was due to a differential ability of the two NS1 proteins to inhibit antiviral responses. This suggests that the subversion of human antiviral responses may be an important requirement for influenza viruses to adapt to the human host and cause disease.

  17. Possible role of phosphoinositide-3-kinase in Mx1 protein translation and antiviral activity of interferon-omega-stimulated HeLa cells.

    Science.gov (United States)

    Seo, Youngjun; Kim, Mihee; Choi, Minjoung; Kim, Sunhee; Park, Kidae; Oh, Ilung; Chung, Seungtae; Suh, Hongwon; Hong, Seunghwa; Park, Suenie

    2011-01-01

    Interferon ω (IFN-ω), a cytokine released during innate immune activation, is well known for promoting direct antiviral responses; however, the possible signal pathways that are initiated by IFN-ω binding to the type I IFN receptors have not been fully studied. Here, we provide evidence that activation of phosphoinositide-3-kinase/protein kinase B (PI3K/Akt) signaling plays a pivotal role in the generation of IFN-ω-mediated biological responses. We found that LY294002 (PI3K inhibitor)-attenuated antiviral activities are induced by IFN-ω treatment. Although such effects of LY294002 are unrelated to regulatory activities on IFN-ω-dependent Mx1 (myxovirus resistance 1) or Mx2 gene transcriptional regulation, translation of Mx1 protein, which was known as a key mediator of cell-autonomous antiviral resistance, was significantly reduced by PI3K inhibition. Further studies showed that PI3K inhibition using LY294002 leads to a decrease in PI3K substrate Akt and mitogen-activated protein kinase extracellular signal-regulated kinase and p38 phosphorylation/activation. In addition, although LY294002 was not able to reduce STAT1 activation, we found that the mammalian target of rapamycin (mTOR)/p70 S6 kinase pathway was significantly attenuated by inhibition of the PI3K/Akt signaling pathway. These results indicate that the PI3K/Akt pathway is a common and central integrator for antiviral responses in IFN-ω signaling via its regulatory effects on mTOR that are required for initiation of mRNA translation of Mx genes.

  18. 76 FR 71560 - Notice of a Public Meeting on Long Term 2 Enhanced Surface Water Treatment Rule: Initiate...

    Science.gov (United States)

    2011-11-18

    ... AGENCY Notice of a Public Meeting on Long Term 2 Enhanced Surface Water Treatment Rule: Initiate Regulatory Review--Cryptosporidium Analytical Method Improvements and Update on Source Water Monitoring... Water Treatment Rule (LT2 rule). This is the first of at least two meetings on the LT2 rule that...

  19. Cost-effectiveness of early-initiated treatment for advanced-stage epithelial ovarian cancer patients: a modeling study

    NARCIS (Netherlands)

    Hoyer, T.; Bekkers, R.L.; Gooszen, H.G.; Massuger, L.F.A.G.; Rovers, M.M.; Grutters, J.P.C.

    2014-01-01

    OBJECTIVE: Between diagnosis and primary treatment of patients with epithelial ovarian cancer (EOC), gaps of several weeks exist. Reducing these time intervals may benefit the patient and may lead to a reduction of costs. We explored the cost-effectiveness of early-initiated treatment of patients wi

  20. ANTIVIRAL POTENTIAL OF MEDICINAL PLANTS: AN OVERVIEW

    Directory of Open Access Journals (Sweden)

    Ruwali Pushpa

    2013-06-01

    Full Text Available The term ‘Antiviral agents’ has been defined in very broad terms as substances other than a virus or virus containing vaccine or specific antibody which can produce either a protective or therapeutic effect to the clear detectable advantage of the virus infected host. The herbal medicine has a long traditional use and the major advantage over other medicines is their wide therapeutic window with rare side effects. There are some disadvantages of synthetic drugs like narrow therapeutic window and more importantly the various adverse side effects which occur quite frequently. Due to these disadvantages and other limitations, there is an increasing trend in the field of research for discovering new and noble drugs based on various herbal formulations. This review attempts to address the importance of developing therapeutic herbal formulations from various medicinal plants using the knowledge based on traditional system of medicines, the Ayurveda. Although natural products have been used by civilization since ancient times, only in recent decades has there been growing research into alternative therapies and the therapeutics use of natural products, especially those derived from plants. Plants synthesize and preserve a variety of biochemical products, many of which are extractable and used for various scientific investigations. Therefore, medicinal plants proved to be a major resort for the treatment of diseases and sicknesses by traditional healers in many societies.

  1. Probiotics as Antiviral Agents in Shrimp Aquaculture

    Directory of Open Access Journals (Sweden)

    Bestha Lakshmi

    2013-01-01

    Full Text Available Shrimp farming is an aquaculture business for the cultivation of marine shrimps or prawns for human consumption and is now considered as a major economic and food production sector as it is an increasingly important source of protein available for human consumption. Intensification of shrimp farming had led to the development of a number of diseases, which resulted in the excessive use of antimicrobial agents, which is finally responsible for many adverse effects. Currently, probiotics are chosen as the best alternatives to these antimicrobial agents and they act as natural immune enhancers, which provoke the disease resistance in shrimp farm. Viral diseases stand as the major constraint causing an enormous loss in the production in shrimp farms. Probiotics besides being beneficial bacteria also possess antiviral activity. Exploitation of these probiotics in treatment and prevention of viral diseases in shrimp aquaculture is a novel and efficient method. This review discusses the benefits of probiotics and their criteria for selection in shrimp aquaculture and their role in immune power enhancement towards viral diseases.

  2. Probiotics as antiviral agents in shrimp aquaculture.

    Science.gov (United States)

    Lakshmi, Bestha; Viswanath, Buddolla; Sai Gopal, D V R

    2013-01-01

    Shrimp farming is an aquaculture business for the cultivation of marine shrimps or prawns for human consumption and is now considered as a major economic and food production sector as it is an increasingly important source of protein available for human consumption. Intensification of shrimp farming had led to the development of a number of diseases, which resulted in the excessive use of antimicrobial agents, which is finally responsible for many adverse effects. Currently, probiotics are chosen as the best alternatives to these antimicrobial agents and they act as natural immune enhancers, which provoke the disease resistance in shrimp farm. Viral diseases stand as the major constraint causing an enormous loss in the production in shrimp farms. Probiotics besides being beneficial bacteria also possess antiviral activity. Exploitation of these probiotics in treatment and prevention of viral diseases in shrimp aquaculture is a novel and efficient method. This review discusses the benefits of probiotics and their criteria for selection in shrimp aquaculture and their role in immune power enhancement towards viral diseases.

  3. Polar profile of antiviral peptides from AVPpred Database.

    Science.gov (United States)

    Polanco, Carlos; Samaniego, José Lino; Castañón-González, Jorge Alberto; Buhse, Thomas

    2014-11-01

    Diseases of viral origin in humans are among the most serious threats to health and the global economy. As recent history has shown the virus has a high pandemic potential, among other reasons, due to its ability to spread by air, hence the identification, investigation, containment, and treatment of viral diseases should be considered of paramount importance. In this sense, the bioinformatics research has focused on finding fast and efficient algorithms that can identify highly toxic antiviral peptides and to serve as a first filter, so that trials in the laboratory are substantially reduced. The work presented here contributes to this effort through the use of an algorithm already published by this team, called polarity index method, which identifies with high efficiency antiviral peptides from the exhaustive analysis of the polar profile, using the linear sequence of the peptide. The test carried out included all peptides in APD2 Database and 60 antiviral peptides identified by Kumar and co-workers (Nucleic Acids Res 40:W199-204, 2012), to build its AVPpred algorithm. The validity of the method was focused on its discriminating capacity so we included the 15 sub-classifications of both Databases.

  4. Antiviral drug discovery against SARS-CoV.

    Science.gov (United States)

    Wu, Yu-Shan; Lin, Wen-Hsing; Hsu, John T-A; Hsieh, Hsing-Pang

    2006-01-01

    Severe Acute Respiratory Syndrome (SARS) is a life-threatening infectious disease caused by SARS-CoV. In the 2003 outbreak, it infected more than 8,000 people worldwide and claimed the lives of more than 900 victims. The high mortality rate resulted, at least in part, from the absence of definitive treatment protocols or therapeutic agents. Although the virus spreading has been contained, due preparedness and planning, including the successful development of antiviral drugs against SARS-CoV, is necessary for possible reappearance of SARS. In this review, we have discussed currently available strategies for antiviral drug discovery and how these technologies have been utilized to identify potential antiviral agents for the inhibition of SARS-CoV replication. Moreover, progress in the drug development based on different molecular targets is also summarized, including 1) Compounds that block the S protein-ACE2-mediated viral entry; 2) Compounds targeting SARS-CoV M(pro); 3) Compounds targeting papain-like protease 2 (PLP2); 4) Compounds targeting SARS-CoV RdRp; 5) Compounds targeting SARS-CoV helicase; 6) Active compounds with unspecified targets; and 7) Research on siRNA. This review aims to provide a comprehensive account of drug discovery on SARS. The experiences with the SARS outbreak and drug discovery would certainly be an important lesson for the drug development for any new viral outbreaks that may emerge in the future.

  5. Antiviral activity of lanatoside C against dengue virus infection.

    Science.gov (United States)

    Cheung, Yan Yi; Chen, Karen Caiyun; Chen, Huixin; Seng, Eng Khuan; Chu, Justin Jang Hann

    2014-11-01

    Dengue infection poses a serious threat globally due to its recent rapid spread and rise in incidence. Currently, there is no approved vaccine or effective antiviral drug for dengue virus infection. In response to the urgent need for the development of an effective antiviral for dengue virus, the US Drug Collection library was screened in this study to identify compounds with anti-dengue activities. Lanatoside C, an FDA approved cardiac glycoside was identified as a candidate anti-dengue compound. Our data revealed that lanatoside C has an IC50 of 0.19μM for dengue virus infection in HuH-7 cells. Dose-dependent reduction in dengue viral RNA and viral proteins synthesis were also observed upon treatment with increasing concentrations of lanatoside C. Time of addition study indicated that lanatoside C inhibits the early processes of the dengue virus replication cycle. Furthermore, lanatoside C can effectively inhibit all four serotypes of dengue virus, flavivirus Kunjin, alphavirus Chikungunya and Sindbis virus as well as the human enterovirus 71. These findings suggest that lanatoside C possesses broad spectrum antiviral activity against several groups of positive-sense RNA viruses.

  6. Initiation of glucose-lowering treatment decreases international normalized ratio levels among users of vitamin K antagonists

    DEFF Research Database (Denmark)

    Stage, Tore Bjerregaard; Pottegård, Anton; Henriksen, Daniel Pilsgaard

    2016-01-01

    -lowering treatment affects international normalized ratio (INR) and dose requirements of the anticoagulant VKAs warfarin and phenprocoumon. PATIENTS/METHODS: We performed a self-controlled retrospective register-based study. A total of 118 patients initiating glucose-lowering treatment while being treated......-lowering treatment reduces the anticoagulant effect of VKA to an extent that is likely to be clinically relevant. This finding needs confirmation and mechanistic explanation. This article is protected by copyright. All rights reserved....

  7. Antiviral therapy for hepatitis B virus associated hepatic failure

    Institute of Scientific and Technical Information of China (English)

    Yu-Ming Wang; Ying-Zi Tang

    2009-01-01

    BACKGROUND: Chronic hepatitis B virus (HBV) infection remains a major global health issue, and the prognosis of patients with HBV-associated fulminant hepatic failure is extremely poor. The application of antiviral therapies has led to signiifcant improvements in patient outcomes. This article aimed to review the current strategies in antiviral treatment of HBV-associated fulminant hepatic failure. DATA SOURCES: Literature search was conducted using PubMed on the related subjects. Part of the data was from the most recent work of the authors' laboratory. RESULTS: Hepatitis B immunoglobulin in prevention of recurrent HBV infection after orthotopic liver transplantation (OLT) has been proven effective. However, its cost is high, and signiifcant side effects have been found to induce viral mutations. Lamivudine has a potent suppression for HBV replication and an excellent safety proifle in decompensated cirrhotic patients, but its major drawback is the high rate of drug-resistance. Adefovir is effective for lamivudine-resistance strains in the post-OLT situation, and its drug-resistance rate is relatively low. Combination therapies such as hepatitis B immunoglobulin combined with lamivudine and lamivudine combined with adefovir have been widely adopted for prophylaxis against HBV recurrence of infection after OLT. Entecavir, telbivudine, tenofovir and other newer agents have been widely used in antiviral therapy. CONCLUSIONS: The prognosis of HBV-associated ful-minant hepatic failure is being transformed by developments in antiviral therapy. However, it should be noticed that HBV is controlled but never eliminated, and drug-resistance still remains a major issue. Hopefully, newer strategies may help to solve these problems.

  8. Current management and recommendations for access to antiviral therapy of herpes labialis.

    Science.gov (United States)

    Cunningham, Anthony; Griffiths, Paul; Leone, Peter; Mindel, Adrian; Patel, Rajul; Stanberry, Lawrence; Whitley, Richard

    2012-01-01

    Herpes labialis is a common skin infective condition, worldwide, which is primarily caused by HSV-1. Recurrent episodes of herpes labialis, also known as cold sores, can be frequent, painful, long-lasting and disfiguring for infected patients. At present, there are two types of antivirals for the treatment of herpes labialis, topical and oral, which are available over the counter or as prescription-only. The aim of antiviral therapy is to block viral replication to enable shortening the duration of symptoms and to accelerate healing of the lesions associated with herpes labialis. This review examines the evidence for the effectiveness of current topical and oral antivirals in the management of recurrent episodes of herpes labialis. In most countries, oral antivirals for herpes labialis are available as prescription-only. However, in early 2010, the oral antiviral famciclovir was reclassified from prescription-only medicine to pharmacist-controlled status in New Zealand. The benefits and risks associated with moving an antiviral therapy for herpes labialis from prescription-only to pharmacist-controlled status are reviewed here, and the implications for patients, general physicians and pharmacists are considered.

  9. Antiviral therapy and outcomes of patients with pneumonia caused by influenza A pandemic (H1N1 virus.

    Directory of Open Access Journals (Sweden)

    Shi-gui Yang

    Full Text Available BACKGROUND: There is limited data on the clinical outcome of patients with pandemic H1N1 (pH1N1 pneumonia who received oseltamivir treatment, especially when the treatment was administered more than 48 hours after symptom onset. METHODS: During the pandemic in 2009, a cohort of pH1N1 influenza pneumonia was built in China, and their clinical information was collected systematically, and analyzed with Cox models. RESULTS: 920 adults and 541 children with pneumonia who didn't receive corticosteroids were analyzed. In-hospital mortality was higher in adults who did not receive antiviral therapy (18.2% than those with who received oseltamivir ≤ 2 days (2.9%, between 2-5 days (4.6% and >5 days after illness onset (4.9%, p5 days, respectively. For males patients, aged ≥ 14 years and baseline PaO(2/FiO(23.8 mg/kg/d did not improve clinical outcome (mortality, higher dose 2.5% vs standard dose 2.8%, p>0.05. CONCLUSIONS: Antiviral therapy might reduce mortality of patients with pH1N1 pneumonia, even when initiated more than 48 hours after onset of illness. Greater protective effects might be in males, patients aged 14-60 years, and patients with PaO(2/FiO(2<200.

  10. Splenectomy with chemotherapy vs surgery alone as initial treatment for splenic marginal zone lymphoma

    Institute of Scientific and Technical Information of China (English)

    Rajko Milosevic; Milena Todorovic; Bela Balint; Miodrag Jevtic; Miodrag Krstic; Elizabeta Ristanovic; Nebojsa Antonijevic; Mirjana Pavlovic; Maja Perunicic; Milan Petrovic; Biljana Mihaljevic

    2009-01-01

    AIM:To evaluate the clinical characteristics of splenic marginal-zone lymphoma (SMZL) following antigen expression and the influence of therapeutic approaches on clinical outcome and overall survival (OS).METHODS:A total of 30 patients with typical histological and immunohistochemical SMZL patterns were examined.Splenectomy plus chemotherapy was applied in 20 patients,while splenectomy as a single treatment-option was performed in 10 patients.Prognostic factor and overall survival rate were analyzed.RESULTS:Complete remission (CR) was achieved in 20 (66.7%),partial remission (PR) in seven (23.3%),and lethal outcome due to disease progression occurred in three (10.0%) patients.Median survival of patients with a splenectomy was 93.0 mo and for patients with splenectomy plus chemotherapy it was 107.5 mo (Log rank=0.056,P>0.05).Time from onset of first symptoms to the beginning of the treatment (mean 9.4 mo) was influenced by spleen dimensions,as measured by computerized tomography and ultra-sound (t=2.558,P=0.018).Strong positivity (+++) of CD20 antigen expression in splenic tissue had a positive influence on OS (Log rank = 5.244,P 0.05) effects on the OS.The expression of other antigens (immunohistochemistry) also had no effect on survival-rate,as measured by a χ2 test (P > 0.05).CONCLUSION:Initial splenectomy combined with chemotherapy has been shown to be beneficial due to its advanced remission rate/duration;however,a larger controlled clinical study is required to confirm our findings.

  11. [Standardisation of the Initial Treatment of Severely Burned Patients: The Necessary Transfer of Concepts from Trauma Care].

    Science.gov (United States)

    Münzberg, M; Harbers, T; Kneser, U; Grützner, P A; Reichert, B; Kremer, T; Wölfl, C G; Horter, J; Hirche, C

    2016-12-01

    The initial treatment of severely burned patients remains a huge challenge for first responders in emergency services as well as emergency doctors who do not work in a centre for severe burn injuries. The reason for this is the low number of cases in developed countries and a lack of training concepts for the specific aspects of the initial treatment of severe burn injuries. Because of guidelines with limited evidence (S1, S2k) and a lack of structured treatment approaches, uncertainties with respect to initial treatment are still visible. Even within the professional societies and on international comparison, controversial aspects remain. In contrast, optimised and standardised procedures are available for the treatment of severely injured (trauma) patients, based on PHTLS® (Pre Hospital Trauma Life Support) for preclinical and ATLS® (Advanced Trauma Life Support) for in-hospital first aid. This article takes stock of the current structure of care and the relevant evidence for the initial treatment of severe burns. Also it discusses a possible transfer and further development of concepts for primary trauma care by all disciplines involved. Nine essential steps in the primary care of burned patients are identified and evaluated. The need for the introduction of a uniform treatment algorithm is illustrated. The treatment algorithm presented in this article addresses all first responders who are faced with initial treatment in the first 24 hours outside of burn centres. As an essential, new aspect, it offers a transfer and adaptation of concepts from trauma care to standardise the care of severely burned patients.

  12. Mathematical analysis of multiscale models for hepatitis C virus dynamics under therapy with direct-acting antiviral agents.

    Science.gov (United States)

    Rong, Libin; Perelson, Alan S

    2013-09-01

    Chronic hepatitis C virus (HCV) infection remains a world-wide public health problem. Therapy with interferon and ribavirin leads to viral elimination in less than 50% of treated patients. New treatment options aiming at a higher cure rate are focused on direct-acting antiviral agents (DAAs), which directly interfere with different steps in the HCV life cycle. In this paper, we describe and analyze a recently developed multiscale model that predicts HCV dynamics under therapy with DAAs. The model includes both intracellular viral RNA replication and extracellular viral infection. We calculate the steady states of the model and perform a detailed stability analysis. With certain assumptions we obtain analytical approximations of the viral load decline after treatment initiation. One approximation agrees well with the prediction of the model, and can conveniently be used to fit patient data and estimate parameter values. We also discuss other possible ways to incorporate intracellular viral dynamics into the multiscale model.

  13. Danish recommendations on treatment of ankylosing spondylitis and spondyloarthritis based on multinational project initiative

    DEFF Research Database (Denmark)

    Pedersen, Susanne Juhl; Madsen, Ole Rintek; Erlendsson, J.

    2008-01-01

    INTRODUCTION: The multinational initiative "3e Initiative in Rheumatology - Multi-national Recommendations for the Management of Ankylosing Spondylitis 2006-7" served the primary purpose of providing specific recommendations for the management of ankylosing spondylitis and spondyloarthritis...

  14. Pilot scale test of a produced water-treatment system for initial removal of organic compounds

    Energy Technology Data Exchange (ETDEWEB)

    Sullivan, Enid J [Los Alamos National Laboratory; Kwon, Soondong [UT-AUSTIN; Katz, Lynn [UT-AUSTIN; Kinney, Kerry [UT-AUSTIN

    2008-01-01

    A pilot-scale test to remove polar and non-polar organics from produced water was performed at a disposal facility in Farmington NM. We used surfactant-modified zeolite (SMZ) adsorbent beds and a membrane bioreactor (MBR) in combination to reduce the organic carbon content of produced water prior to reverse osmosis (RO). Reduction of total influent organic carbon (TOC) to 5 mg/L or less is desirable for efficient RO system operation. Most water disposed at the facility is from coal-bed gas production, with oil production waters intermixed. Up to 20 gal/d of produced water was cycled through two SMZ adsorbent units to remove volatile organic compounds (BTEX, acetone) and semivolatile organic compounds (e.g., napthalene). Output water from the SMZ units was sent to the MBR for removal of the organic acid component of TOC. Removal of inorganic (Mn and Fe oxide) particulates by the SMZ system was observed. The SMZ columns removed up to 40% of the influent TOC (600 mg/L). BTEX concentrations were reduced from the initial input of 70 mg/L to 5 mg/L by the SMZ and to an average of 2 mg/L after the MBR. Removal rates of acetate (input 120-170 mg/L) and TOC (input up to 45 mg/L) were up to 100% and 92%, respectively. The water pH rose from 8.5 to 8.8 following organic acid removal in the MBR; this relatively high pH was likely responsible for observed scaling of the MBR internal membrane. Additional laboratory studies showed the scaling can be reduced by metered addition of acid to reduce the pH. Significantly, organic removal in the MBR was accomplished with a very low biomass concentration of 1 g/L throughout the field trial. An earlier engineering evaluation shows produced water treatment by the SMZ/MBR/RO system would cost from $0.13 to $0.20 per bbl at up to 40 gpm. Current estimated disposal costs for produced water are $1.75 to $4.91 per bbl when transportation costs are included, with even higher rates in some regions. Our results suggest that treatment by an SMZ

  15. Effect of N2 microplasma treatment on initial growth of GaN by metal-organic molecular beam epitaxy

    Science.gov (United States)

    Suzuki, Yohei; Kusakabe, Yasuhiro; Uchiyama, Shota; Maruyama, Takahiro; Naritsuka, Shigeya; Shimizu, Kazuo

    2016-08-01

    N2 atmospheric microplasma was applied to improve the yields and reproducibility of the initial growth of GaN by metal-organic molecular beam epitaxy (MOMBE). The plasma treatment was found to be effective in cleaning the surface, and excellent flat growth was achieved even in the early stage of the growth. The effect of the air exposure after plasma treatment was also studied, and the yield of the growth was found to be largely decreased by the air exposure even after the treatment. Therefore, the oxidation of the substrate is one of main causes of the poor initial growth and the installation of the microplasma equipment in the MBE loading chamber is useful for suppressing the oxidation after the treatment. Atomic force microscopy (AFM) measurement shows that the microplasma treatment is also effective for undoing the surface double steps through etching, which is helpful for a very smooth layer-by-layer growth in the early stage of growth.

  16. Triple antiviral therapy with telaprevir after liver transplantation: a case series

    Directory of Open Access Journals (Sweden)

    Knapstein J

    2014-09-01

    Full Text Available Johanna Knapstein,1 Daniel Grimm,1 Marcus A Wörns,1 Peter R Galle,1 Hauke Lang,2 Tim Zimmermann111st Department of Internal Medicine, Johannes Gutenberg-University, Mainz, Germany; 2Department of General, Visceral and Transplantation Surgery, Johannes Gutenberg-University, Mainz, GermanyIntroduction: Hepatitis C virus (HCV reinfection occurs universally after liver transplantation, with accelerated cirrhosis rates of up to 30% within 5 years after liver transplantation. Dual antiviral therapy with pegylated interferon-2a (peg-IFN and ribavirin (RBV only reaches sustained virological response rates of ~30% after liver transplantation. With the approval of viral NS3/4A protease inhibitors telaprevir (TVR, boceprevir, and simeprevir and the NS5B polymerase inhibitor sofosbuvir, combination therapy offers new therapeutic options for HCV-infected patients, resulting in considerably higher sustained virological response rates in the nontransplant setting. Case presentation: We report three cases of TVR-based triple antiviral therapy in HCV genotype 1 reinfected patients after liver transplantation, of whom a 57-year-old Caucasian female and a 43-year-old Caucasian male were therapy naïve, and a 49-year-old Caucasian male patient was pretreated ineffectively. After 4 weeks of therapy, viral load decreased one to three log10 and became negative in weeks 6 to 8 in the therapy naïve patients. The pretreated patient showed a negative viral load in week 4. TVR was administered over 12 weeks, 750 mg thrice daily. Doses of immunosuppression with cyclosporine were reduced four to six fold. Initial peg-IFN and RBV doses ranged from 135–180 µg/week and 800–1,200 mg/day, according to the patient's body weight. Doses of peg-IFN and RBV were adapted to 90–135 µg/week and 400–800 mg/day after 2 to 12 weeks of protease inhibitor therapy. Dual therapy was continued for 36 weeks with total treatment duration of 48 weeks in the therapy naïve patients

  17. Containing pandemic influenza with antiviral agents.

    Science.gov (United States)

    Longini, Ira M; Halloran, M Elizabeth; Nizam, Azhar; Yang, Yang

    2004-04-01

    For the first wave of pandemic influenza or a bioterrorist influenza attack, antiviral agents would be one of the few options to contain the epidemic in the United States until adequate supplies of vaccine were available. The authors use stochastic epidemic simulations to investigate the effectiveness of targeted antiviral prophylaxis to contain influenza. In this strategy, close contacts of suspected index influenza cases take antiviral agents prophylactically. The authors compare targeted antiviral prophylaxis with vaccination strategies. They model an influenza pandemic or bioterrorist attack for an agent similar to influenza A virus (H2N2) that caused the Asian influenza pandemic of 1957-1958. In the absence of intervention, the model predicts an influenza illness attack rate of 33% of the population (95% confidence interval (CI): 30, 37) and an influenza death rate of 0.58 deaths/1,000 persons (95% Cl: 0.4, 0.8). With the use of targeted antiviral prophylaxis, if 80% of the exposed persons maintained prophylaxis for up to 8 weeks, the epidemic would be contained, and the model predicts a reduction to an illness attack rate of 2% (95% Cl: 0.2, 16) and a death rate of 0.04 deaths/1,000 persons (95% CI: 0.0003, 0.25). Such antiviral prophylaxis is nearly as effective as vaccinating 80% of the population. Vaccinating 80% of the children aged less than 19 years is almost as effective as vaccinating 80% of the population. Targeted antiviral prophylaxis has potential as an effective measure for containing influenza until adequate quantities of vaccine are available.

  18. Antiviral therapy effects upon hepatitis C cholestatic syndrome.

    Science.gov (United States)

    Vere, C C; Gofiţă, Eliza; Forţofoiu, C; Streba, Letiţia Adela Maria; Genunche, Amelia

    2007-01-01

    Cholestasis includes, as a syndrome, all clinical and biological manifestations caused by the deficient or simply absent biliar secretion or caused by the obstruction of the biliary ducts. The hepatic cholestasis from the chronic hepatitis C (HC VHC) is a result of the altered interlobular biliary canalicules, caused by the modified cellular transport mechanisms and it is associated with a medium to severe degree of fibrosis. The aim of this study was to evaluate the efficiency of antiviral therapy in HC VHC patients. The study included a number of 37 HC VHC patients admitted at the Medical Department no. 1 of the Emergency County Hospital of Craiova; they were treated with Pegasys, 180 microg/week and Copegus, 1000 or 1200 mg/day, taking in consideration their weight, for 48 weeks and they were monitored for 24 weeks after the treatment. The following parameters were analyzed: direct bilirubine, total cholesterol, alkaline phosphatase, gamma-glutamiltranspeptidase and leucin-aminopeptidase. Under treatment, the clinical status caused by the cholestasis (pruritus, icteric syndrome, hemoragipary syndrome) was improved in six of the given cases (16.22%). Before therapy, the hepatic cholestasis was present in 20 patients (54.05%), and after treatment in 14 patients (37.83%). During therapy, the average values for all the monitored parameters decreased: direct bilirubine (0.38 +/- 0.18 mg/dl vs. 0.34 +/- 0.24 mg/dl, p = 0.0867), total cholesterol (198.53 md/dl vs. 183.16 mg/dl, p = 0.0808), alkaline phosphatase (236.99 +/- 79.09 iu/l vs. 227.82 +/- 87.59 iu/l, p = 0.0845), gamma-glutamiltranspeptidase (47 +/- 32.89 iu/l vs. 43.91 +/- 29.66 iu/l, p = 0.1509), and leucin-aminopeptidase (32.33 +/- 13.22 iu/l vs. 28.95 +/- 14.22 iu/l, p = 0.0038). Under antiviral treatment there was noticed an improvement of the cholestasis clinical status in a small number of cases. Antiviral therapy favorably influenced the liver cholestasis associated in patients with chronic hepatitis

  19. The impact of initial statin treatment decisions on cardiovascular outcomes in clinical care settings: estimates using the Archimedes Model

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    van Herick A

    2012-11-01

    Full Text Available Andrew van Herick,1 C Andy Schuetz,1 Peter Alperin,1 Michael Bullano,2 Sanjeev Balu,2 Sanjay Gandhi21Archimedes, Inc, San Francisco, CA, USA; 2AstraZeneca Pharmaceuticals LP, Wilmington, DE, USAPurpose: Many patients treated for dyslipidemia do not achieve recommended cholesterol goals despite the widespread availability of effective statins. Pharmaceutical claims show a strong tendency for patients to remain on their initially assigned treatment. With computer simulations, the impact of initial statin treatment decisions on medium- and long-term cardiovascular outcomes were examined.Patients and methods: Using the Archimedes Model, three treatment scenarios were simulated. Patients initiated treatment with simvastatin (20, 40, or 80 mg, atorvastatin (10, 20, 40, or 80 mg, or rosuvastatin (10, 20, or 40 mg, and periodically intensified treatment. The simulated population consisted of 50,025 patients, aged 45–70 years, with low-density lipoprotein cholesterol exceeding goal. The proportion of patients initiating each dose was calibrated to United States pharmacy claims. Patients not reaching goal intensified the dose of their current statin or switched to an appropriate dose of rosuvastatin at rates matching pharmacy claims. Biomarkers and major adverse cardiovascular events (MACE were tracked for 10 years and several high-risk subpopulations were analyzed. Statin models used biomarker effects from the STELLAR (Statin Therapies for Elevated Lipid Levels Compared Across Doses to Rosuvastatin trial and outcomes data from various trials.Results: Initiating therapy with rosuvastatin reduced MACE more than simvastatin or atorvastatin. The 5- year relative risk of MACE was 0.906 (95% confidence interval: 0.888–0.923; P < 0.001 for initial treatment with atorvastatin rather than simvastatin, 0.831 (0.812–0.850; P < 0.001 for rosuvastatin rather than simvastatin, and 0.918 (0.898–0.938; P < 0.001 for rosuvastatin rather than atorvastatin

  20. Antiviral activities of heated dolomite powder.

    Science.gov (United States)

    Motoike, Koichi; Hirano, Shozo; Yamana, Hideaki; Onda, Tetsuhiko; Maeda, Takayoshi; Ito, Toshihiro; Hayakawa, Motozo

    2008-12-01

    The effect of the heating conditions of dolomite powder on its antiviral activity was studied against the H5N3 avian influenza virus. Calcium oxide (CaO) and magnesium oxide (MgO), obtained by the thermal decomposition of dolomite above 800 degrees C, were shown to have strong antiviral activity, but the effect was lessened when the heating temperature exceeded 1400 degrees C. Simultaneous measurement of the crystallite size suggested that the weakening of the activity was due to the considerable grain growth of the oxides. It was found that the presence of Mg in dolomite contributed to the deterrence of grain growth of the oxides during the heating process. Although both CaO and MgO exhibited strong antiviral activity, CaO had the stronger activity but quickly hydrated in the presence of water. On the other hand, the hydration of MgO took place gradually under the same conditions. Separate measurements using MgO and Mg(OH)2 revealed that MgO had a higher antiviral effect than Mg(OH)2. From the overall experiments, it was suggested that the strong antiviral activity of dolomite was related to the hydration reaction of CaO.

  1. Prognostic Significance of Initial Serum Albumin and 24 Hour Daily Protein Excretion before Treatment in Multiple Myeloma.

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    Jia-Hong Chen

    Full Text Available Renal failure is a common morbidity in multiple myeloma (MM. Although proteinuria has been increasingly reported in malignancies, it is not routinely used to refine risk estimates of survival outcomes in patients with MM. Here we aimed to investigate initial serum albumin and 24-hour daily protein excretion (24-h DPE before treatment as prognostic factors in patients with MM. We conducted a retrospective analysis of 102 patients with myeloma who were ineligible for haematopoietic stem cell transplantation between October 2000 and December 2012. Initial proteinuria was assessed before treatment by quantitative analysis of 24-hour urine samples. The demographic and laboratory characteristics, survival outcome, and significance of pre-treatment 24-h DPE and albumin in the new staging system of MM were analyzed. Pre-treatment proteinuria (>300 mg/day was present in 66 patients (64.7%. The optimal cut-off value of 24-h DPE before treatment was 500 mg/day. Analysis of the time-dependent area under the curve showed that the serum albumin and 24-h DPE before treatment were better than 24-h creatinine clearance rate and β2-microglobulin. A subgroup analysis showed that an initial excess proteinuria (24-h DPE ≥ 500 mg was associated with poor survival status (17.51 vs. 34.24 months, p = 0.002. Furthermore, initial serum albumin was an independent risk factor on multivariate analysis (<2.8 vs. ≥ 2.8, hazard ratio = 0.486, p = 0.029. Using the A-DPE staging system, there was a significant survival difference among patients with stage I, II, and III MM (p < 0.001. Initial serum albumin and 24-h DPE before treatment showed significant prognostic factors in patients with MM, and the new A-DPE staging system may be utilized instead of the International Staging System. Its efficacy should be evaluated by further large prospective studies.

  2. Integrative Genomics-Based Discovery of Novel Regulators of the Innate Antiviral Response

    NARCIS (Netherlands)

    Lee, R. van der; Feng, Q.; Langereis, M.A.; Horst, R. ter; Szklarczyk, R.J.; Netea, M.G.; Andeweg, A.C.; Kuppeveld, F.J.M. van; Huynen, M.A.

    2015-01-01

    The RIG-I-like receptor (RLR) pathway is essential for detecting cytosolic viral RNA to trigger the production of type I interferons (IFNalpha/beta) that initiate an innate antiviral response. Through systematic assessment of a wide variety of genomics data, we discovered 10 molecular signatures of

  3. Integrative Genomics-Based Discovery of Novel Regulators of the Innate Antiviral Response

    NARCIS (Netherlands)

    van der Lee, Robin; Feng, Qian; Langereis, Martijn A; Ter Horst, Rob; Szklarczyk, Radek; Netea, Mihai G; Andeweg, Arno C; van Kuppeveld, Frank J M; Huynen, Martijn A

    2015-01-01

    The RIG-I-like receptor (RLR) pathway is essential for detecting cytosolic viral RNA to trigger the production of type I interferons (IFNα/β) that initiate an innate antiviral response. Through systematic assessment of a wide variety of genomics data, we discovered 10 molecular signatures of known R

  4. Integrative Genomics-Based Discovery of Novel Regulators of the Innate Antiviral Response

    NARCIS (Netherlands)

    R. van der Lee (Robin); Q. Feng (Qian); M.A. Langereis (Martijn A.); R. ter Horst (Rob); R. Szklarczyk (Radek); M.G. Netea (Mihai); A.C. Andeweg (Arno); F.J.M. van Kuppeveld (Frank ); M. Huynen (Martijn)

    2015-01-01

    textabstractThe RIG-I-like receptor (RLR) pathway is essential for detecting cytosolic viral RNA to trigger the production of type I interferons (IFNα/β) that initiate an innate antiviral response. Through systematic assessment of a wide variety of genomics data, we discovered 10 molecular signature

  5. Distribution of vaccine/antivirals and the 'least spread line' in a stratified population

    NARCIS (Netherlands)

    Goldstein, E.; Apolloni, A.; Lewis, B.; Miller, J. C.; Macauley, M.; Eubank, S.; Lipsitch, M.; Wallinga, J.

    2010-01-01

    We describe a prioritization scheme for an allocation of a sizeable quantity of vaccine or antivirals in a stratified population. The scheme builds on an optimal strategy for reducing the epidemic's initial growth rate in a stratified mass-action model. The strategy is tested on the EpiSims network

  6. Association between serum lipid levels and antiviral treatment outcome in patients with chronic hepatitis C%血脂水平与慢性丙型肝炎患者抗病毒疗效的相关性分析

    Institute of Scientific and Technical Information of China (English)

    时佳; 沈震; 苗慧; 杨宗国; 徐庆年; 陆云飞; 吕莹; 陈晓蓉

    2014-01-01

    目的:分析慢性丙型肝炎(CHC)患者血脂水平与抗病毒疗效的相关性,为评估预后、指导治疗提供依据。方法纳入2010年1月至2013年8月收治的171例CHC初治患者,给予聚乙二醇干扰素(PEG-IFN)及利巴韦林抗病毒治疗,分析比较不同应答情况、基因型及治疗0、12及24周(非1b型)或0、24及48周(1b型)患者血清总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白(LDL-C)、高密度脂蛋白(HDL-C)、载脂蛋白A(apoA)、载脂蛋白B(apoB)水平。正态分布计量资料采用t检验及方差分析;非正态分布资料采用秩和检验;分类变量采用χ2检验。采用单因素及多因素Logistic回归分析筛选与患者预后相关的预测因子。结果171例CHC PEG-IFN及利巴韦林抗病毒初治患者治疗后,获得持续病毒学应答(SVR)率及未获得持续病毒学应答(non-SVR)率分别为81.87%、18.13%,SVR组患者TG、apoB明显较non-SVR组患者低(P<0.05)。基因3型CHC患者TC、LDL-C、apoA及apoB均较基因1b、6a型患者低;ALT、AST水平相比较高(P<0.05)。SVR组患者TG、apoB在治疗结束时升高,HDL-C降低(P<0.05);non-SVR组患者血脂水平在治疗过程中无明显改变。单因素Logistic分析示患者年龄≤50岁、基因型非1b型、TG≤3.11 mmol/L、apoB≤0.63 g/L与SVR密切相关(P<0.05);多因素回归分析表明,年龄≤50岁及apoB≤0.63 g/L CHC患者易获得SVR(P<0.05)。结论本研究提示,血脂水平和年龄与CHC患者抗病毒疗效密切相关,年龄≤50岁和apoB≤0.63 g/L是CHC患者SVR的独立预测因素。%Objective To investigate the association between serum lipid levels and antiviral treatment outcome in chronic hepatitis C (CHC)patients.Methods A total of 171 treatment-naive CHC patients were included in the present retrospective study and received a standard therapy of

  7. The study of antiviral activity of the dietary supplement «Immuno-viral with vitamin C» against influenza A/Victoria virus strains

    Directory of Open Access Journals (Sweden)

    Ганна Сергіївна Шумова

    2016-01-01

    Full Text Available The implementation of combined remedies, having in their composition herbal material, that shows anti-inflammatory, antibacterial, antiviral, restorative, and immunotropic action, is one of promising directions in the search of effective agents for acute respiratory infections prevention and treatment.Aim. The purpose of our research was to determine antiviral activity of the dietary supplement «Immuno-viral with Vitamin C» in the form of hard capsules against influenza A/Victoria virus strains.Methods. Classic virological method of chick embryos contamination in the chorioallantoic membrane, immunofluorescence method for the obtained virus identification, and neutralization reaction in chick embryos has been used.Results. It has been determined that the dietary supplement components were non-toxic for chick embryos in dilution of 1:10 to 1:80; had antiviral activity against influenza A/Victoria prototype virus strain in dilution of 1:10 to 1:20; lethal toxic dose in dilution of 1:40. After administration of influenza A/Victoria prototype virus strain in chick embryos without incubation with the test remedy (passaging, the medicinal agent retained its initial properties, confirmed by infected embryo cells fluorescence and the further study of the subcultered strain in the inhibition hemagglutination test with chick erythrocytes.Conclusion. As a result of the carried out in experiment neutralization reaction in 9–11 days chick embryos by the method of contamination in the chorioallantoic membrane with further visualization and identification of material, containing the virus, by the immunofluorescence method of the infected cells specific fluorescence, antiviral properties of the dietary supplement «Immuno-viral with Vitamin C» components have been determined

  8. The efficiency of intratympanic dexamethasone injection as a sequential treatment after initial systemic steroid therapy for sudden sensorineural hearing loss.

    Science.gov (United States)

    Lee, Jong Bin; Choi, Seong Jun; Park, Keehyun; Park, Hun Yi; Choo, Oak-Sung; Choung, Yun-Hoon

    2011-06-01

    The effect of intratympanic steroid injection is controversial as salvage or initial treatment option for sudden sensorineural hearing loss (SSNHL) and almost unknown if it is consecutively to use after initial systemic steroids. This study aimed to analyze the efficiency of intratympanic dexamethasone injection (ITDI) as a sequential treatment in the patients who failed initial systemic steroid treatments for SSNHL. Forty-six patients with SSNHL who did not respond to initial systemic steroids were prospectively included in the study. The patients were randomly classified into two groups; the ITDI group (21 patients) did not take four sequential ITDI within 2 weeks after systemic steroids, and the control group (25 patients) took any more medications. Hearing improvement was defined as a 10 dB or more decrease in the pure tone average (PTA) of the four-frequencies (0.5, 1, 2, and 3 kHz). Hearing improvement was observed in 10 (47.6%) of 21 ITDI patients and in 4 (16.0%) of 25 control patients (P = 0.027). An improvement of the mean PTA was 11.4 dB in the ITDI group and 1.7 dB in the control group (P = 0.004). The ITDI group showed significant hearing improvement at low frequency (500 Hz) than the control group. The patients with 70 or more dB in PTA before ITDI showed significant hearing improvement than the other patients with better PTAs (P = 0.038). The sequential ITDI, which is performed immediately after initial systemic steroid therapy, may be a simple, effective second-line treatment of choice for the patients who show poor response to initial treatments for SSNHL.

  9. Antiviral activity of Acacia nilotica against Hepatitis C Virus in liver infected cells

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    Javed Tariq

    2011-05-01

    Full Text Available Abstract Hepatitis C virus (HCV belonging to the family Flaviviridae has infected 3% of the population worldwide and 6% of the population in Pakistan. The only recommended standard treatment is pegylated INF-α plus ribavirin. Due to less compatibility of the standard treatment, thirteen medicinal plants were collected from different areas of Pakistan on the basis of undocumented antiviral reports against different viral infections. Medicinal plants were air dried, extracted and screened out against HCV by infecting HCV inoculums of 3a genotype in liver cells. RT-PCR results demonstrate that acetonic and methanolic extract of Acacia nilotica (AN showed more than 50% reduction at non toxic concentration. From the above results, it can be concluded that by selecting different molecular targets, specific structure-activity relationship can be achieved by doing mechanistic analysis. So, additional studies are required for the isolation and recognition of antiviral compound in AN to establish its importance as antiviral drug against HCV. For further research, we will scrutinize the synergistic effect of active antiviral compound in combination with standard PEG INF-α and ribavirin which may be helpful in exploring further gateways for antiviral therapy against HCV.

  10. Evaluation of antiviral activity of essential oil of Trachyspermum Ammi against Japanese encephalitis virus

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    Soumen Roy

    2015-01-01

    Full Text Available Background: Japanese encephalitis is a leading form of viral encephalitis, prevalent mostly in South Eastern Asia caused by Japanese encephalitis virus (JEV. It is transmitted by the mosquitoes of the Culex sp. The disease affects children and results in 50% result in permanent neuropsychiatric disorder. There arises a need to develop a safe, affordable, and potent anti-viral agent against JEV. This study aimed to assess the antiviral activity of ajwain (Trachyspermum ammi: Umbellifereae essential oil against JEV. Materials and Methods: Ajwain oil was extracted by distillation method and in vitro cytotoxicity assay was performed in vero cell line by 3-(4, 5-dimethylthiazol-2-yl-2, 5-diphenyltetrazolium bromide (MTT assay method. JEV titer was determined by plaque assay and in vitro antiviral activity of ajwain oil was quantified by the plaque reduction neutralization test (PRNT. Results: Cytotoxic concentration of the oil was found to be 1 mg/ml by MTT assay. The titer of the virus pool was found to be 50× 10 7 PFU/ml. we observed 80% and 40% virus inhibition in 0.5mg/ml of ajwain oil by PRNT method in preexposure treatment and postexposure treatment (antiviral activity, respectively. Conclusion: Our data indicate ajwain oil has potential in vitro antiviral activity against JEV. Further, the active biomolecule will be purified and evaluated for anti-JEV activity and also to scale up for in vivo trial to evaluate the efficacy of ajwain oil in future.

  11. A fresh look at an antiviral helicase

    Institute of Scientific and Technical Information of China (English)

    Leonid Gitlin; Marco Colonna

    2007-01-01

    @@ In order to survive,all organlsms must guard against viral infections.Recognition of viruses is accomplished via multiple sensors.Many mammalian proteins can recognize viral products,such as double-stranded RNA(dsRNA),yet feW of them are known to induce interferon,the central antiviral messenger.Since interferon is indispensable for Successful antiviral defense [1],the interferon-inducing sensors have been of particular interest.However,a clear understanding of such sensors has been elusive,and the first well-established sensor family,the toll-like receptors (TLRs),was described relatively recently[2].Antiviral TLRS are positioned in the endosomes,where they report the appearance of viral genetic material(DNA,single-and double-stranded RNA).

  12. Experimental rhinovirus infection in COPD: implications for antiviral therapies.

    Science.gov (United States)

    Gunawardana, Natasha; Finney, Lydia; Johnston, Sebastian L; Mallia, Patrick

    2014-02-01

    Chronic obstructive pulmonary disease (COPD) is a major public health problem and will be one of the leading global causes of mortality over the coming decades. Much of the morbidity, mortality and health care costs of COPD are attributable to acute exacerbations, the commonest causes of which are respiratory infections. Respiratory viruses are frequently detected in COPD exacerbations but direct proof of a causative relationship has been lacking. We have developed a model of COPD exacerbation using experimental rhinovirus infection in COPD patients and this has established a causative relationship between virus infection and exacerbations. In addition it has determined some of the molecular mechanisms linking virus infections to COPD exacerbations and identified potential new therapeutic targets. This new data should stimulate research into the role of antiviral agents as potential treatments for COPD exacerbations. Testing of antiviral agents has been hampered by the lack of a small animal model for rhinovirus infection and experimental rhinovirus infection in healthy volunteers has been used to test treatments for the common cold. Experimental rhinovirus infection in COPD subjects offers the prospect of a model that can be used to evaluate the effects of new treatments for virus-induced COPD exacerbations, and provide essential data that can be used in making decisions regarding large scale clinical trials.

  13. Specifically targeted antiviral therapy for hepatitis C virus

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Hepatitis C virus (HCV) infection affects 180 million people worldwide with the predominant prevalence being infection with genotype 1, followed by genotypes 2 and 3. Standard anti-HCV therapy currently aims to enhance natural immune responses to the virus, whereas new therapeutic concepts directly target HCV RNA and viral enzymes or influence host-virus interactions. Novel treatment options now in development are focused on inhibitors of HCV-specific enzymes, NS3 protease and NS5B polymerase.These agents acting in concert represent the concept of specifically targeted antiviral therapy for HCV (STAT-C).STAT-C is an attractive strategy in which the main goal is to increase the effectiveness of antiviral responses across all genotypes, with shorter treatment duration and better tolerability. However, the emergence of resistant mutations that limit the use of these compounds in monotherapy complicates the regimens. Thus, a predictable scenario for HCV treatment in the future will be combinations of drugs with distinct mechanisms of action. For now, it seems that interferon will remain a fundamental component of any new anti-HCV therapeutic regimens in the near future;therefore, there is pressure to develop forms of interferon that are more effective, less toxic, and more convenient than pegylated interferon.

  14. Antiviral Activity of Natural Products Extracted from Marine Organisms

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    Sobia Tabassum

    2011-11-01

    Full Text Available Many epidemics have broken out over the centuries. Hundreds and thousands of humans have died over a disease. Available treatments for infectious diseases have always been limited. Some infections are more deadly than the others, especially viral pathogens. These pathogens have continuously resisted all kinds of medical treatment, due to a need for new treatments to be developed. Drugs are present in nature and are also synthesized in vitro and they help in combating diseases and restoring health. Synthesizing drugs is a hard and time consuming task, which requires a lot of man power and financial aid. However, the natural compounds are just lying around on the earth, may it be land or water. Over a thousand novel compounds isolated from marine organisms are used as antiviral agents. Others are being pharmacologically tested. Today, over forty antiviral compounds are present in the pharmacological market. Some of these compounds are undergoing clinical and pre-clinical stages. Marine compounds are paving the way for a new trend in modern medicine.

  15. Drosophila as a model for antiviral immunity

    Institute of Scientific and Technical Information of China (English)

    Susanna; Valanne; Mika; Rmet

    2010-01-01

    The fruit fly Drosophila melanogaster has been successfully used to study numerous biological processes including immune response.Flies are naturally infected with more than twenty RNA viruses making it a valid model organism to study host-pathogen interactions during viral infections.The Drosophila antiviral immunity includes RNA interference,activation of the JAK/STAT and other signaling cascades and other mechanisms such as autophagy and interactions with other microorganisms.Here we review Drosophila as an immunological research model as well as recent advances in the field ofDrosophila antiviral immunity.

  16. Parents report on stimulant-treated children in the Netherlands : Initiation of treatment and follow-up care

    NARCIS (Netherlands)

    Faber, Adrianne; Kalverdijk, Luuk J.; de Jong-van den Berg, Lolkje T. W.; Hugtenburg, Jacqueline G.; Minderaa, Ruud B.; Tobi, Hilde

    2006-01-01

    Objectives: The aim of this study was to describe current practices around initiation and follow-up care of stimulant treatment among stimulant-treated children in a nationwide survey among parents. Methods: A total of 115 pharmacies detected current stimulant users <16 years old in their pharmacy i

  17. Predicting Post-Treatment-Initiation Alcohol Use among Patients with Severe Mental Illness and Alcohol Use Disorders

    Science.gov (United States)

    Bradizza, Clara M.; Maisto, Stephen A.; Vincent, Paula C.; Stasiewicz, Paul R.; Connors, Gerard J.; Mercer, Nicole D.

    2009-01-01

    Few investigators studying alcohol abuse among individuals with a severe mental illness (SMI) have examined predictors of posttreatment alcohol outcomes. In the present study, a multivariate approach based on a theoretical model was used to study the relationship between psychosocial factors and post-treatment-initiation alcohol use. Predictors of…

  18. Prognostic Significance of Initial Serum Albumin and 24 Hour Daily Protein Excretion before Treatment in Multiple Myeloma.

    Science.gov (United States)

    Chen, Jia-Hong; Hsu, Shun-Neng; Huang, Tzu-Chuan; Wu, Yi-Ying; Lin, Chin; Chang, Ping-Ying; Chen, Yeu-Chin; Ho, Ching-Liang

    2015-01-01

    Renal failure is a common morbidity in multiple myeloma (MM). Although proteinuria has been increasingly reported in malignancies, it is not routinely used to refine risk estimates of survival outcomes in patients with MM. Here we aimed to investigate initial serum albumin and 24-hour daily protein excretion (24-h DPE) before treatment as prognostic factors in patients with MM. We conducted a retrospective analysis of 102 patients with myeloma who were ineligible for haematopoietic stem cell transplantation between October 2000 and December 2012. Initial proteinuria was assessed before treatment by quantitative analysis of 24-hour urine samples. The demographic and laboratory characteristics, survival outcome, and significance of pre-treatment 24-h DPE and albumin in the new staging system of MM were analyzed. Pre-treatment proteinuria (>300 mg/day) was present in 66 patients (64.7%). The optimal cut-off value of 24-h DPE before treatment was 500 mg/day. Analysis of the time-dependent area under the curve showed that the serum albumin and 24-h DPE before treatment were better than 24-h creatinine clearance rate and β2-microglobulin. A subgroup analysis showed that an initial excess proteinuria (24-h DPE ≥ 500 mg) was associated with poor survival status (17.51 vs. 34.24 months, p = 0.002). Furthermore, initial serum albumin was an independent risk factor on multivariate analysis (albumin and 24-h DPE before treatment showed significant prognostic factors in patients with MM, and the new A-DPE staging system may be utilized instead of the International Staging System. Its efficacy should be evaluated by further large prospective studies.

  19. Initiation of Addiction Treatment and Access to Services: Young Adults' Accounts of Their Help-Seeking Experiences.

    Science.gov (United States)

    Wagner, Vincent; Bertrand, Karine; Flores-Aranda, Jorge; Acier, Didier; Brunelle, Natacha; Landry, Michel; Brochu, Serge

    2016-12-04

    Substance addiction in young adults is particularly problematic. Yet, much remain at stake in understanding the specifics of this population's access to services. The objective of this study is to explore young adults' initiation of substance misuse treatment. Our study sample was composed of 35 individuals aged 18 to 30 with problematic psychoactive substance use who have been identified in criminal courts, hospital emergency departments, and Health and Social Services Centers in Québec (Canada). A thematic analysis was performed on the 62 semi-structured interviews conducted with participants. Three components emerged. First, personal elements-expectations, individual motivations, perceptions of use, and capacity to control it-influence initiation of substance misuse treatment. Second, family and peers have noticeable influences. Finally, system characteristics and prior care experiences also shape the process. Consideration should be given to tailor interventions that can reach young adults and encourage them to initiate appropriate care.

  20. SOME ASPECTS OF THE MARKETING STUDIES FOR THE PHARMACEUTICAL MARKET OF ANTIVIRAL DRUGS

    Directory of Open Access Journals (Sweden)

    A. G. Salnikova

    2015-01-01

    Full Text Available Antiviral drugs are widely used in medicinal practice. They suppress the originator and stimulate the protection of an organism. The drugs are used for the treatment of flu and ARVI, herpetic infections, virus hepatitis, HIV-infection. Contemporary pharmaceutical market is represented by a wide range of antiviral drugs. Marketing studies are conducted to develop strategies, used for the enhancement of pharmacy organization activity efficiency. Conduction of the marketing researches of pharmaceutical market is the purpose of this study. We have used State Registry of Drugs, State Record of Drugs, List of vital drugs, questionnaires of pharmaceutical workers during our work. Historical, sociological, mathematical methods, and a method of expert evaluation were used in the paper. As the result of the study we have made the following conclusions. We have studied and generalized the literature data about classification and application of antiviral drugs, marketing, competition. The assortment of antiviral drugs on the pharmaceutical market of the Russian Federation was also studied. We have conducted an analysis for the obtainment of the information about antiviral drugs by pharmaceutical workers. We have determined the competitiveness of antiviral drugs, and on the basis of the research conducted we have submitted an offer for pharmaceutical organizations to form the range of antiviral drugs.

  1. Effect of Traditional Chinese Medicine Antiviral Capsules On Animal Model Genital Herpes and HSV-2 in Cell Culture

    Institute of Scientific and Technical Information of China (English)

    范瑞强; 李红毅; 谢长才; 禤国维; 朱宇同

    2001-01-01

    Objective: To study the effect of traditional Chinese medicine antiviral capsules in the treatment of genital herpes.Methods: Using female guinea pig genital herpes as the animal model, this study used oral administration of two formulations of antiviral capsules (AC) and observed the effect on vaginal HSV-2 titers and vulvar symptoms. Cell cultures were also used to examine the direct inactivation of HSV-2 by the antiviral capsules and the suppression of HSV-2 via three drug administration methods.Results: There was no significant difference of mean vaginal virus titers between the antiviral capsule groups and that of the positive acyclovir (ACV) control (P>0.05). Mean vulvar symptom scores of the two antiviral capsule groups were also significantly lower than that of the saline negative control group on days 2, 3, 5, 7 and 8 (P<0.05) and similar to that of the ACV control (P>0.05). Cell culture showed the minimum inhibitory concentrations of antiviral capsules No. 1 and No. 2 were 0.390625 mg/ml and 1,5625 mg/ml, respectively.Conclusion: The traditional Chinese medicine antiviral capsules had suppressive effects on HSV-2 in both animal model GH and in vitro cell culture.

  2. Durations and Delays in Care Seeking, Diagnosis and Treatment Initiation in Uncomplicated Pulmonary Tuberculosis Patients in Mumbai, India.

    Directory of Open Access Journals (Sweden)

    Nerges Mistry

    Full Text Available Timely diagnosis and treatment initiation are critical to reduce the chain of transmission of Tuberculosis (TB in places like Mumbai, where almost 60% of the inhabitants reside in overcrowded slums. This study documents the pathway from the onset of symptoms suggestive of TB to initiation of TB treatment and examines factors responsible for delay among uncomplicated pulmonary TB patients in Mumbai.A population-based retrospective survey was conducted in the slums of 15 high TB burden administrative wards to identify 153 self-reported TB patients. Subsequently in-depth interviews of 76 consenting patients that fit the inclusion criteria were undertaken using an open-ended interview schedule. Mean total, first care seeking, diagnosis and treatment initiation duration and delays were computed for new and retreatment patients. Patients showing defined delays were divided into outliers and non-outliers for all three delays using the median values.The mean duration for the total pathway was 65 days with 29% of patients being outliers. Importantly the mean duration of first care seeking was similar in new (24 days and retreatment patients (25 days. Diagnostic duration contributed to 55% of the total pathway largely in new patients. Treatment initiation was noted to be the least among the three durations with mean duration in retreatment patients twice that of new patients. Significantly more female patients experienced diagnostic delay. Major shift of patients from the private to public sector and non-allopaths to allopaths was observed, particularly for treatment initiation.Achieving positive behavioural changes in providers (especially non-allopaths and patients needs to be considered in TB control strategies. Specific attention is required in counselling of TB patients so that timely care seeking is effected at the time of relapse. Prioritizing improvement of environmental health in vulnerable locations and provision of point of care diagnostics

  3. Analysis of correlation between initial alveolar bone density and apical root resorption after 12 months of orthodontic treatment without extraction

    Directory of Open Access Journals (Sweden)

    Paula Cabrini Scheibel

    2014-10-01

    Full Text Available OBJECTIVE: The aim of the present study was to investigate the correlation between initial alveolar bone density of upper central incisors (ABD-UI and external apical root resorption (EARR after 12 months of orthodontic movement in cases without extraction. METHODS: A total of 47 orthodontic patients 11 years old or older were submitted to periapical radiography of upper incisors prior to treatment (T1 and after 12 months of treatment (T2. ABD-UI and EARR were measured by means of densitometry. RESULTS: No statistically significant correlation was found between initial ABD-UI and EARR at T2 (r = 0.149; p = 0.157. CONCLUSION: Based on the present findings, alveolar density assessed through periapical radiography is not predictive of root resorption after 12 months of orthodontic treatment in cases without extraction.

  4. More Chemotherapy May Help after Initial Treatment for Childhood Leukemia Fails

    Science.gov (United States)

    A study suggests that at least some children diagnosed with acute lymphoblastic leukemia who respond poorly to initial chemotherapy may do better if they receive additional chemotherapy rather than a stem cell transplant.

  5. The Impact of a Line Probe Assay Based Diagnostic Algorithm on Time to Treatment Initiation and Treatment Outcomes for Multidrug Resistant TB Patients in Arkhangelsk Region, Russia

    Science.gov (United States)

    Eliseev, Platon; Balantcev, Grigory; Nikishova, Elena; Gaida, Anastasia; Bogdanova, Elena; Enarson, Donald; Ornstein, Tara; Detjen, Anne; Dacombe, Russell; Gospodarevskaya, Elena; Phillips, Patrick P. J.; Mann, Gillian; Squire, Stephen Bertel; Mariandyshev, Andrei

    2016-01-01

    Background In the Arkhangelsk region of Northern Russia, multidrug-resistant (MDR) tuberculosis (TB) rates in new cases are amongst the highest in the world. In 2014, MDR-TB rates reached 31.7% among new cases and 56.9% among retreatment cases. The development of new diagnostic tools allows for faster detection of both TB and MDR-TB and should lead to reduced transmission by earlier initiation of anti-TB therapy. Study Aim The PROVE-IT (Policy Relevant Outcomes from Validating Evidence on Impact) Russia study aimed to assess the impact of the implementation of line probe assay (LPA) as part of an LPA-based diagnostic algorithm for patients with presumptive MDR-TB focusing on time to treatment initiation with time from first-care seeking visit to the initiation of MDR-TB treatment rather than diagnostic accuracy as the primary outcome, and to assess treatment outcomes. We hypothesized that the implementation of LPA would result in faster time to treatment initiation and better treatment outcomes. Methods A culture-based diagnostic algorithm used prior to LPA implementation was compared to an LPA-based algorithm that replaced BacTAlert and Löwenstein Jensen (LJ) for drug sensitivity testing. A total of 295 MDR-TB patients were included in the study, 163 diagnosed with the culture-based algorithm, 132 with the LPA-based algorithm. Results Among smear positive patients, the implementation of the LPA-based algorithm was associated with a median decrease in time to MDR-TB treatment initiation of 50 and 66 days compared to the culture-based algorithm (BacTAlert and LJ respectively, p<0.001). In smear negative patients, the LPA-based algorithm was associated with a median decrease in time to MDR-TB treatment initiation of 78 days when compared to the culture-based algorithm (LJ, p<0.001). However, several weeks were still needed for treatment initiation in LPA-based algorithm, 24 days in smear positive, and 62 days in smear negative patients. Overall treatment outcomes

  6. Antiviral drug resistance of herpes simplex virus

    NARCIS (Netherlands)

    Stranska, Ruzena

    2004-01-01

    Infections with herpes simplex virus (HSV) usually have an asymptomatic or benign course. However, severe infections do occur, particularly in HIV/AIDS patients or transplant recipients, and may be life-threatening unless adequate antiviral therapy is given. Since its introduction in the early 1980

  7. Antiviral Prophylaxis and H1N1

    Centers for Disease Control (CDC) Podcasts

    2011-07-14

    Dr. Richard Pebody, a consultant epidemiologist at the Health Protection Agency in London, UK, discusses the use of antiviral post-exposure prophylaxis and pandemic H1N1.  Created: 7/14/2011 by National Center for Emerging Zoonotic and Infectious Diseases (NCEZID).   Date Released: 7/18/2011.

  8. IFN-gamma: Novel antiviral cytokines

    DEFF Research Database (Denmark)

    Ank, Nina; West, Hans; Paludan, Søren Riis

    2006-01-01

    and adaptive immune responses. Recently, a novel class of cytokines was discovered and named IFN-lambda (alternatively type III IFN or interleukin-28/29 [IL- 28/29]), based on IFN-like antiviral activity and induction of typical IFN-inducible genes. Here, we review the literature on IFN-lambda and discuss...

  9. In vitro comparison of antiviral drugs against feline herpesvirus 1

    Directory of Open Access Journals (Sweden)

    Garré B

    2006-04-01

    Full Text Available Abstract Background Feline herpesvirus 1 (FHV-1 is a common cause of respiratory and ocular disease in cats. Especially in young kittens that have not yet reached the age of vaccination, but already lost maternal immunity, severe disease may occur. Therefore, there is a need for an effective antiviral treatment. In the present study, the efficacy of six antiviral drugs, i.e. acyclovir, ganciclovir, cidofovir, foscarnet, adefovir and 9-(2-phosphonylmethoxyethyl-2, 6-diaminopurine (PMEDAP, against FHV-1 was compared in Crandell-Rees feline kidney (CRFK cells using reduction in plaque number and plaque size as parameters. Results The capacity to reduce the number of plaques was most pronounced for ganciclovir, PMEDAP and cidofovir. IC50 (NUMBER values were 3.2 μg/ml (12.5 μM, 4.8 μg/ml (14.3 μM and 6 μg/ml (21.5 μM, respectively. Adefovir and foscarnet were intermediately efficient with an IC50 (NUMBER of 20 μg/ml (73.2 μM and 27 μg/ml (140.6 μM, respectively. Acyclovir was least efficient (IC50 (NUMBER of 56 μg/ml or 248.7 μM. All antiviral drugs were able to significantly reduce plaque size when compared with the untreated control. As observed for the reduction in plaque number, ganciclovir, PMEDAP and cidofovir were most potent in reducing plaque size. IC50 (SIZE values were 0.4 μg/ml (1.7 μM, 0.9 μg/ml (2.7 μM and 0.2 μg/ml (0.7 μM, respectively. Adefovir and foscarnet were intermediately potent, with an IC50 (SIZE of 4 μg/ml (14.6 μM and 7 μg/ml (36.4 μM, respectively. Acyclovir was least potent (IC50 (SIZE of 15 μg/ml or 66.6 μM. The results demonstrate that the IC50 (SIZE values were notably lower than the IC50 (NUMBER values. The most remarkable effect was observed for cidofovir and ganciclovir. None of the products were toxic for CRFK cells at antiviral concentrations. Conclusion In conclusion, measuring reduction in plaque number and plaque size are two valuable and complementary means of assessing the efficacy of

  10. Cytotoxic, Virucidal, and Antiviral Activity of South American Plant and Algae Extracts

    Directory of Open Access Journals (Sweden)

    Paula Faral-Tello

    2012-01-01

    Full Text Available Herpes simplex virus type 1 (HSV-1 infection has a prevalence of 70% in the human population. Treatment is based on acyclovir, valacyclovir, and foscarnet, three drugs that share the same mechanism of action and of which resistant strains have been isolated from patients. In this aspect, innovative drug therapies are required. Natural products offer unlimited opportunities for the discovery of antiviral compounds. In this study, 28 extracts corresponding to 24 plant species and 4 alga species were assayed in vitro to detect antiviral activity against HSV-1. Six of the methanolic extracts inactivated viral particles by direct interaction and 14 presented antiviral activity when incubated with cells already infected. Most interesting antiviral activity values obtained are those of Limonium brasiliense, Psidium guajava, and Phyllanthus niruri, which inhibit HSV-1 replication in vitro with 50% effective concentration (EC50 values of 185, 118, and 60 μg/mL, respectively. For these extracts toxicity values were calculated and therefore selectivity indexes (SI obtained. Further characterization of the bioactive components of antiviral plants will pave the way for the discovery of new compounds against HSV-1.

  11. Initial evaluation of an integrated treatment for comorbid PTSD and smoking using a nonconcurrent, multiple-baseline design.

    Science.gov (United States)

    Feldner, Matthew T; Smith, Rose C; Monson, Candice M; Zvolensky, Michael J

    2013-09-01

    The present study examined an integrated treatment for comorbid posttraumatic stress disorder (PTSD) and smoking entitled "Smoke-Free to Overcome PTSD: An Integrated Treatment" (STOP IT program). A nonconcurrent multiple-baseline design was used with six community-recruited adult smokers with PTSD to investigate both patient acceptance of the treatment and its initial efficacy on both PTSD and smoking. Potential order effects of exposure-based and affect management components were also examined. A gold-standard assessment strategy that included the Clinician Administered PTSD Scale (Blake et al., 1995) and biochemical verification of self-reported smoking status was employed to measure primary targets of treatment. Results suggested that the STOP IT program was well tolerated. There were clinically significant improvements in PTSD outcomes, but only temporary reductions in smoking. Participants' relatively low posttreatment smoking levels increased by the follow-up assessment, although not to baseline levels. Treatment component order did not appear to affect treatment outcomes, but those who were assigned to the exposure-focused writing prior to affect management training condition appeared more likely to discontinue treatment before beginning exposure. These preliminary data support the safety, acceptability, and potential efficacy of the STOP IT program. Future investigation of the STOP IT program should include testing the incremental efficacy of increasing the dose of smoking-focused intervention, as well as randomized controlled tests of the treatment that employ gold standards for treatment outcome research.

  12. A systemic resistance inducing antiviral protein with N-glycosidase activity from Bougainvillea xbuttiana leaves.

    Science.gov (United States)

    Narwal, S; Balasubrahmanyam, A; Sadhna, P; Kapoor, H; Lodha, M L

    2001-06-01

    An antiviral protein from Bougainvillea xbuttiana leaves induced systemic resistance in host plants N. glutinosa and Cyamopsis tetragonoloba against TMV and SRV, respectively which was reversed by actinomycin D, when applied immediately or shortly after antiviral protein treatment. When the inhibitor was applied to the host plant leaves post inoculation, it was effective if applied upto 4 h after virus infection. It also delayed the expression of symptoms in systemic hosts of TMV. The inhibitor showed characteristic N-glycosidase activity on 25S rRNA of tobacco ribosomes, suggesting that it could also be interfering with virus multiplication through ribosome-inactivation process.

  13. Do herpes zoster patients receive antivirals?: a national survey in general practice.

    NARCIS (Netherlands)

    Opstelten, W.; Essen, G.A. van; Moons, K.G.M.; Wijck, A.J.M. van; Schellevis, F.G.; Kalkman, C.J.; Verheij, T.J.M.

    2005-01-01

    BACKGROUND: The main complications of herpes zoster (HZ) are postherpetic neuralgia and, in case of HZ ophthalmicus, eye disorders. Antiviral treatment may modify the course of disease and reduce the risk of complications. OBJECTIVE: To assess which doctors' and patients' characteristics were relate

  14. Ganciclovir Antiviral Therapy in Advanced Idiopathic Pulmonary Fibrosis: An Open Pilot Study

    Directory of Open Access Journals (Sweden)

    J. J. Egan

    2011-01-01

    Conclusion. This audit outcome suggests that 2-week course of ganciclovir (iv may attenuate disease progression in a subgroup of advanced IPF patients. These observations do not suggest that anti-viral treatment is a substitute for the standard care, however, suggests the need to explore the efficacy of ganciclovir as adjunctive therapy in IPF.

  15. Melittin-loaded immunoliposomes against viral surface proteins, a new approach to antiviral therapy.

    Science.gov (United States)

    Falco, Alberto; Barrajón-Catalán, Enrique; Menéndez-Gutiérrez, María P; Coll, Julio; Micol, Vicente; Estepa, Amparo

    2013-02-01

    In this study, melittin, a well-characterized pore-forming lytic amphiphilic peptide susceptible to be vehiculized in lipid membranes, has been utilized to study their antiviral properties. For this purpose, an assay based on melittin loaded-immunoliposomes previously described by our group was adapted to antiviral purposes by means of monoclonal antibodies targeting the surface G glycoprotein of the fish viral haemorrhagic septicemia rhabdovirus (VHSV). We also studied the antiviral action of these immunoliposomes in vitro and the results showed that they are capable of inhibiting the VHSV infectivity by 95.2% via direct inactivation of the virus. Furthermore, the inhibition of the infectivity when treatments were added at different times post-infection and the analysis of the infection foci sizes suggested altogether that they also act by reducing the VHSV spread in cell culture and by killing the infected cells which express the G glycoprotein in their plasmatic membranes.

  16. Phytochemical screening, cytotoxicity and antiviral activity of hexane fraction of Phaleria macrocarpa fruits

    Science.gov (United States)

    Ismaeel, Mahmud Yusef Yusef; Yaacob, Wan Ahmad; Tahir, Mariya Mohd.; Ibrahim, Nazlina

    2015-09-01

    Phaleria macrocarpa fruits have been widely used in the traditional medicine for the treatment of several infections. The current study was done to determine the phytochemical content, cytotoxicity and antiviral activity of the hexane fraction (HF) of P. macrocarpa fruits. In the hexane fraction of P. macarocarpa fruits, phytochemical screening showed the presence of terpenoids whereas saponins, alkaloids, tannins and anthraquinones were not present. Evaluation on Vero cell lines by using MTT assay showed that the 50% cytotoxic concentration (CC50) value was 0.48 mg/mL indicating that the fraction is not cytotoxic. Antiviral properties of the plant extracts were determined by plaque reduction assay. The effective concentration (EC50) was 0.18 mg/mL. Whereas the selective index (SI = CC50/EC50) of hexane fraction is 2.6 indicating low to moderate potential as antiviral agent.

  17. Delays before Diagnosis and Initiation of Treatment in Patients Presenting to Mental Health Services with Bipolar Disorder.

    Directory of Open Access Journals (Sweden)

    Rashmi Patel

    Full Text Available Bipolar disorder is a significant cause of morbidity and mortality. Although existing treatments are effective, there is often a substantial delay before diagnosis and treatment initiation. We sought to investigate factors associated with the delay before diagnosis of bipolar disorder and the onset of treatment in secondary mental healthcare.Retrospective cohort study using anonymised electronic mental health record data from the South London and Maudsley NHS Foundation Trust (SLaM Biomedical Research Centre (BRC Case Register on 1364 adults diagnosed with bipolar disorder between 2007 and 2012. The following predictor variables were analysed in a multivariable Cox regression analysis: age, gender, ethnicity, compulsory admission to hospital under the UK Mental Health Act, marital status and other diagnoses prior to bipolar disorder. The outcomes were time to recorded diagnosis from first presentation to specialist mental health services (the diagnostic delay, and time to the start of appropriate therapy (treatment delay.The median diagnostic delay was 62 days (interquartile range: 17-243 and median treatment delay was 31 days (4-122. Compulsory hospital admission was associated with a significant reduction in both diagnostic delay (hazard ratio 2.58, 95% CI 2.18-3.06 and treatment delay (4.40, 3.63-5.62. Prior diagnoses of other psychiatric disorders were associated with increased diagnostic delay, particularly alcohol (0.48, 0.33-0.41 and substance misuse disorders (0.44, 0.31-0.61. Prior diagnosis of schizophrenia and psychotic depression were associated with reduced treatment delay.Some individuals experience a significant delay in diagnosis and treatment of bipolar disorder after initiation of specialist mental healthcare, particularly those who have prior diagnoses of alcohol and substance misuse disorders. These findings highlight a need for further study on strategies to better identify underlying symptoms and offer appropriate treatment

  18. Paramedic Initiated Lisinopril For Acute Stroke Treatment (PIL-FAST: study protocol for a pilot randomised controlled trial

    Directory of Open Access Journals (Sweden)

    McColl Elaine

    2011-06-01

    Full Text Available Abstract Background High blood pressure during acute stroke is associated with poorer stroke outcome. Previous trials have failed to show benefit from lowering blood pressure but treatment may have been commenced too late to be effective. The earliest that acute stroke treatments could be initiated is during contact with the emergency medical services (paramedics. However, experience of pre-hospital clinical trials is limited and logistical challenges are likely to be greater than for trials performed in other settings. We report the protocol for a pilot randomised controlled trial of paramedic initiated blood pressure lowering treatment for hypertension in acute stroke. Methods Trial Design: Double blind parallel group external pilot randomised controlled trial. Setting: Participant recruitment and initial treatment by North East Ambulance Service research trained paramedics responding to the emergency call. Continued treatment in three study hospitals. Participants: Target is recruitment of 60 adults with acute arm weakness due to suspected stroke (within 3 hours of symptom onset and hypertension (systolic BP>160 mmHg. Intervention: Lisinopril 5-10 mg (intervention group, matched placebo (control group, daily for 7 days. Randomisation: Study medication contained within identical pre-randomised "trial packs" carried by research trained paramedics. Outcomes: Study feasibility (recruitment rate, compliance with data collection and clinical data to inform the design of a definitive randomised controlled trial (blood pressure monitoring, National Institute of Health Stroke Scale, Barthel ADL Index, Modified Rankin Scale, renal function. Discussion This pilot study is assessing the feasibility of a randomised controlled trial of paramedic initiated lisinopril for hypertension early after the onset of acute stroke. The results will inform the design of a definitive RCT to evaluate the effects of very early blood pressure lowering in acute stroke

  19. TRIM25 Enhances the Antiviral Action of Zinc-Finger Antiviral Protein (ZAP)

    Science.gov (United States)

    Lau, Zerlina; Cheung, Pamela; Schneider, William M.; Bozzacco, Leonia; Buehler, Eugen; Takaoka, Akinori; Rice, Charles M.; Felsenfeld, Dan P.; MacDonald, Margaret R.

    2017-01-01

    The host factor and interferon (IFN)-stimulated gene (ISG) product, zinc-finger antiviral protein (ZAP), inhibits a number of diverse viruses by usurping and intersecting with multiple cellular pathways. To elucidate its antiviral mechanism, we perform a loss-of-function genome-wide RNAi screen to identify cellular cofactors required for ZAP antiviral activity against the prototype alphavirus, Sindbis virus (SINV). In order to exclude off-target effects, we carry out stringent confirmatory assays to verify the top hits. Important ZAP-liaising partners identified include proteins involved in membrane ion permeability, type I IFN signaling, and post-translational protein modification. The factor contributing most to the antiviral function of ZAP is TRIM25, an E3 ubiquitin and ISG15 ligase. We demonstrate here that TRIM25 interacts with ZAP through the SPRY domain, and TRIM25 mutants lacking the RING or coiled coil domain fail to stimulate ZAP’s antiviral activity, suggesting that both TRIM25 ligase activity and its ability to form oligomers are critical for its cofactor function. TRIM25 increases the modification of both the short and long ZAP isoforms by K48- and K63-linked polyubiquitin, although ubiquitination of ZAP does not directly affect its antiviral activity. However, TRIM25 is critical for ZAP’s ability to inhibit translation of the incoming SINV genome. Taken together, these data uncover TRIM25 as a bona fide ZAP cofactor that leads to increased ZAP modification enhancing its translational inhibition activity. PMID:28060952

  20. The initial experience of electronic brachytherapy for the treatment of non-melanoma skin cancer

    Directory of Open Access Journals (Sweden)

    Bhatnagar Ajay

    2010-09-01

    Full Text Available Abstract Background Millions of people are diagnosed with non-melanoma skin cancers (NMSC worldwide each year. While surgical approaches are the standard treatment, some patients are appropriate candidates for radiation therapy for NMSC. High dose rate (HDR brachytherapy using surface applicators has shown efficacy in the treatment of NMSC and shortens the radiation treatment schedule by using a condensed hypofractionated approach. An electronic brachytherapy (EBT system permits treatment of NMSC without the use of a radioactive isotope. Methods Data were collected retrospectively from patients treated from July 2009 through March 2010. Pre-treatment biopsy was performed to confirm a malignant cutaneous diagnosis. A CT scan was performed to assess lesion depth for treatment planning, and an appropriate size of surface applicator was selected to provide an acceptable margin. An HDR EBT system delivered a dose of 40.0 Gy in eight fractions twice weekly with 48 hours between fractions, prescribed to a depth of 3-7 mm. Treatment feasibility, acute safety, efficacy outcomes, and cosmetic results were assessed. Results Thirty-seven patients (mean age 72.5 years with 44 cutaneous malignancies were treated. Of 44 lesions treated, 39 (89% were T1, 1 (2% Tis, 1 (2% T2, and 3 (7% lesions were recurrent. Lesion locations included the nose for 16 lesions (36.4%, ear 5 (11%, scalp 5 (11%, face 14 (32%, and an extremity for 4 (9%. Median follow-up was 4.1 months. No severe toxicities occurred. Cosmesis ratings were good to excellent for 100% of the lesions at follow-up. Conclusions The early outcomes of EBT for the treatment of NMSC appear to show acceptable acute safety and favorable cosmetic outcomes. Using a hypofractionated approach, EBT provides a convenient treatment schedule.

  1. Characteristics of U.S. substance abuse treatment facilities adopting buprenorphine in its initial stage of availability.

    Science.gov (United States)

    Koch, Alison L; Arfken, Cynthia L; Schuster, Charles R

    2006-07-27

    This study examined the adoption of buprenorphine for the treatment of opiate dependence among U.S. substance abuse treatment facilities and their characteristics at the time of the initial availability of the medication. Data come from a 2003 national survey of all substance abuse treatment facilities in the U.S. Out of our sample of 13,060 facilities, 5.5% of facilities reported they offered buprenorphine. Not unexpectedly, the prevalence was higher in certified opioid treatment programs (11.3%) compared to other facilities (4.6%). For opioid treatment programs, offering Naltrexone (OR=8.34, 95% CI=5.53, 12.58) and offering medically supervised withdrawal (OR=2.76, 95% CI=1.38, 5.52) were independent and robust predictors of offering buprenorphine. These same variables were independent predictors for the non-opioid treatment programs as well (Naltrexone, OR=14.32, 95% CI=7.85, 26.10; and medically supervised withdrawal services, OR=4.42, 95% CI=3.01, 6.49). Our results suggest that the adoption of buprenorphine soon after the Food and Drug Administration approved its use for treatment of opioid dependence and the shipping of the medication commenced was associated with facilities already offering pharmacotherapies such as Naltrexone and medically assisted withdrawal. These findings provide baseline data to track the adoption of buprenorphine by substance abuse treatment programs in future years.

  2. Induction maintenance concept for HAART as initial treatment in HIV infected infants

    Directory of Open Access Journals (Sweden)

    Ghosh S

    2011-06-01

    Full Text Available Abstract Background Early initiated antiretroviral therapy (ART in HIV infected infants leads to improved long-term viral suppression and survival. Guidelines recommend initiating therapy with a triple ART consisting of two nucleoside reverse transcriptase inhibitors (NRTIs and either one additional non-nucleoside reverse transcriptase inhibitor (NNRTI or a protease inhibitor (PI. Compared to older children and adults, viral relapse is seen more frequently in infants receiving triple ART. We now address the possibility of a more potent ART with a quadruple induction and triple maintenance therapy. Methods We examine the longitudinal course in four HIV infected infants, who were referred from other centers and could not be recruited to multicentre trials. We introduced ART initially consisting of two NRTIs, one NNRTI and one PI and later discontinued the PI at the age of 12 months maintaining a triple regime consisting of two NRTIs and one NNRTI. Results Provided that therapy adherence was maintained we observed an effective sustained decline of viral load and significant CD4 cell reconstitution even after switching to a triple regime. No drug associated toxicity was seen. Conclusion We suggest that a four drug therapy might be a possible initial therapy option in HIV infected infants, at least in those with a high viral load, followed by a maintenance triple regime after 12 months of therapy.

  3. Development and initial evaluation of blended cognitive behavioural treatment for major depression in routine specialized mental health care

    DEFF Research Database (Denmark)

    Kooistra, L. C.; Ruwaard, J.; Wiersma, J. E.

    2016-01-01

    the costs of mental health care, by reducing treatment duration and/or therapist contact. However, knowledge on blended care for depression is still limited. Objectives: To develop a blended cognitive behavioural treatment (bCBT) for depressed patients in an outpatient specialized mental health care centre...... and to conduct a preliminary evaluation of this bCBT protocol. Method: A bCBT protocol was developed, taking recommendations into account from depressed patients (n = 3) and therapists and experts in the field of e-health (n = 18). Next, an initial evaluation of integrated high-intensive bCBT was conducted...... with depressed patients (n = 9) in specialized mental health care. Patients' clinical profiles were established based on pre-treatment diagnostic information and patient self-reports on clinical measures. Patient treatment adherence rates were explored, together with patient ratings of credibility and expectancy...

  4. Eligibility of persons who inject drugs for treatment of hepatitis C virus infection.

    Science.gov (United States)

    Arain, Amber; Robaeys, Geert

    2014-09-28

    In this decade, an increase is expected in end-stage liver disease and hepatocellular carcinoma, most commonly caused by hepatitis C virus (HCV) infection. Although people who inject drugs (PWID) are the major source for HCV infection, they were excluded from antiviral treatments until recently. Nowadays there is incontrovertible evidence in favor of treating these patients, and substitution therapy and active substance use are no longer contraindications for antiviral treatment. The viral clearance in PWID after HCV antiviral treatment with interferon or pegylated interferon combined with ribavirin is comparable to the viral clearance in non-substance users. Furthermore, multidisciplinary approaches to delivering treatment to PWID are advised, and their treatment should be considered on an individualized basis. To prevent the spread of HCV in the PWID community, recent active PWID are eligible for treatment in combination with needle exchange programs and substitution therapy. As the rate of HCV reinfection is low after HCV antiviral treatment, there is no need to withhold HCV treatment due to concerns about reinfection alone. Despite the advances in treatment efficacies and data supporting their success, HCV assessment of PWID and initiation of antiviral treatment remains low. However, the proportion of PWID assessed and treated for HCV is increasing, which can be further enhanced by understanding the barriers to and facilitators of HCV care. Removing stigmatization and implementing peer support and group treatment strategies, in conjunction with greater involvement by nurse educators/practitioners, will promote greater treatment seeking and adherence by PWID. Moreover, screening can be facilitated by noninvasive methods for detecting HCV antibodies and assessing liver fibrosis stages. Recently, HCV clearance has become a major endpoint in the war against drugs for the Global Commission on Drug Policy. This review highlights the most recent evidence concerning

  5. Letermovir and inhibitors of the terminase complex: a promising new class of investigational antiviral drugs against human cytomegalovirus

    Directory of Open Access Journals (Sweden)

    Melendez DP

    2015-08-01

    Full Text Available Dante P Melendez,1,2 Raymund R Razonable1,2 1Division of Infectious Diseases, 2William J von Liebig Center for Transplantation and Clinical Regeneration, Mayo Clinic, Rochester, MN, USA Abstract: Infection with cytomegalovirus is prevalent in immunosuppressed patients. In solid organ transplant and hematopoietic stem cell transplant recipients, cytomegalovirus infection is associated with high morbidity and preventable mortality. Prevention and treatment of cytomegalovirus with currently approved antiviral drugs is often associated with side effects that sometimes preclude their use. Moreover, cytomegalovirus has developed mutations that confer resistance to standard antiviral drugs. During the last decade, there have been calls to develop novel antiviral drugs that could provide better options for prevention and treatment of cytomegalovirus. Letermovir (AIC246 is a highly specific antiviral drug that is currently undergoing clinical development for the management of cytomegalovirus infection. It acts by inhibiting the viral terminase complex. Letermovir is highly potent in vitro and in vivo against cytomegalovirus. Because of a distinct mechanism of action, it does not exhibit cross-resistance with other antiviral drugs. It is predicted to be active against strains that are resistant to ganciclovir, foscarnet, and cidofovir. To date, early-phase clinical trials suggest a very low incidence of adverse effects. Herein, we present a comprehensive review on letermovir, from its postulated novel mechanism of action to the results of most recent clinical studies. Keywords: cytomegalovirus, letermovir, AIC246, terminase, antivirals, transplantation 

  6. Early Surgery versus Initial Conservative Treatment in Patients with Traumatic Intracerebral Hemorrhage (STITCH[Trauma]): The First Randomized Trial.

    Science.gov (United States)

    Mendelow, A David; Gregson, Barbara A; Rowan, Elise N; Francis, Richard; McColl, Elaine; McNamee, Paul; Chambers, Iain R; Unterberg, Andreas; Boyers, Dwayne; Mitchell, Patrick M

    2015-09-01

    Intraparenchymal hemorrhages occur in a proportion of severe traumatic brain injury TBI patients, but the role of surgery in their treatment is unclear. This international multi-center, patient-randomized, parallel-group trial compared early surgery (hematoma evacuation within 12 h of randomization) with initial conservative treatment (subsequent evacuation allowed if deemed necessary). Patients were randomized using an independent randomization service within 48 h of TBI. Patients were eligible if they had no more than two intraparenchymal hemorrhages of 10 mL or more and did not have an extradural or subdural hematoma that required surgery. The primary outcome measure was the traditional dichotomous split of the Glasgow Outcome Scale obtained by postal questionnaires sent directly to patients at 6 months. The trial was halted early by the UK funding agency (NIHR HTA) for failure to recruit sufficient patients from the UK (trial registration: ISRCTN19321911). A total of 170 patients were randomized from 31 of 59 registered centers worldwide. Of 82 patients randomized to early surgery with complete follow-up, 30 (37%) had an unfavorable outcome. Of 85 patients randomized to initial conservative treatment with complete follow-up, 40 (47%) had an unfavorable outcome (odds ratio, 0.65; 95% confidence interval, CI 0.35, 1.21; p=0.17), with an absolute benefit of 10.5% (CI, -4.4-25.3%). There were significantly more deaths in the first 6 months in the initial conservative treatment group (33% vs. 15%; p=0.006). The 10.5% absolute benefit with early surgery was consistent with the initial power calculation. However, with the low sample size resulting from the premature termination, we cannot exclude the possibility that this could be a chance finding. A further trial is required urgently to assess whether this encouraging signal can be confirmed.

  7. Antiretroviral treatment initiation does not differentially alter neurocognitive functioning over time in youth with behaviorally acquired HIV

    OpenAIRE

    Nichols, Sharon L.; Bethel, James; Kapogiannis, Bill G.; Li, Tiandong; Woods, Steven P.; Patton, E. Doyle; Ren, Weijia; Thornton, Sarah E.; Major-Wilson, Hanna O.; Puga, Ana M.; Sleasman, John W.; Rudy, Bret J; Craig M Wilson; Garvie, Patricia A.; ,

    2015-01-01

    Although youth living with behaviorally acquired HIV (YLWH) are at risk for cognitive impairments, the relationship of impairments to HIV and potential to improve with antiretroviral therapy (ART) are unclear. This prospective observational study was designed to examine the impact of initiation and timing of ART on neurocognitive functioning in YLWH in the Adolescent Medicine Trials Network for HIV/AIDS Interventions. Treatment naïve YLWH age 18–24 completed baseline and four additional asses...

  8. Pain and discomfort perceived during the initial stage of active fixed orthodontic treatment

    Science.gov (United States)

    Rakhshan, Hamid; Rakhshan, Vahid

    2015-01-01

    Background and objectives As the most common complication of orthodontic treatment, pain can negatively impact quality of life and cause patients to discontinue treatment. However, few studies have evaluated pain during orthodontic treatment, with controversial findings. This study assessed the intensity and duration of pain and discomfort caused by active orthodontic treatment. Methods This descriptive cross-sectional study examined 67 patients (22 men, 45 females; age range: 18–32 years) undergoing fixed orthodontic treatment. Patients were interviewed after the active treatment stage to assess their perceived pain and discomfort at different sites during different activities by a visual analogue scale. Frequency and duration of pain in different areas were analyzed by the chi-squared and chi-squared goodness-of-fit tests (α = 0.05). Results Among the 67 patients, 65.7% experienced general dentogingival pain or discomfort and 34.3% had localized dentogingival pain or discomfort (p = 0.010, chi-squared goodness-of-fit test). Masticating soft foods reduced discomfort (p = 0.000, chi-squared) in the tongue, cheeks, and in or around the teeth and gingivae. Pain and discomfort were mostly moderate while masticating sticky, fibrous, and firm foods. Mild pains were mostly reported during tooth brushing and while consuming soft foods (p < 0.05, chi-squared). Pain and discomfort tended to last for more than 4 weeks, except in the tongue, where pain and discomfort lasted less than 4 weeks (p < 0.05, chi-squared goodness-of-fit test). Conclusions Pain and discomfort occur for more than 4 weeks after beginning fixed orthodontic treatment. Changing diets to incorporate softer foods is recommended to alleviate pain. PMID:26082574

  9. Antiviral potential of lactic acid bacteria and their bacteriocins.

    Science.gov (United States)

    Al Kassaa, I; Hober, D; Hamze, M; Chihib, N E; Drider, D

    2014-12-01

    Emerging resistance to antiviral agents is a growing public health concern worldwide as it was reported for respiratory, sexually transmitted and enteric viruses. Therefore, there is a growing demand for new, unconventional antiviral agents which may serve as an alternative to the currently used drugs. Meanwhile, published literature continues shedding the light on the potency of lactic acid bacteria (LAB) and their bacteriocins as antiviral agents. Health-promoting LAB probiotics may exert their antiviral activity by (1) direct probiotic-virus interaction; (2) production of antiviral inhibitory metabolites; and/or (3) via stimulation of the immune system. The aim of this review was to highlight the antiviral activity of LAB and substances they produce with antiviral activity.

  10. Impact of introducing the line probe assay on time to treatment initiation of MDR-TB in Delhi, India.

    Directory of Open Access Journals (Sweden)

    Neeta Singla

    Full Text Available SETTING: National Institute of Tuberculosis and Respiratory Diseases (erstwhile Lala Ram Sarup Institute in Delhi, India. OBJECTIVES: To evaluate before and after the introduction of the line Probe Assay (LPA a the overall time to MDR-TB diagnosis and treatment initiation; b the step-by-step time lapse at each stage of patient management; and c the lost to follow-up rates. METHODS: A retrospective cohort analysis was done using data on MDR-TB patients diagnosed during 2009-2012 under Revised National Tuberculosis Control Programme at the institute. RESULTS: Following the introduction of the LPA in 2011, the overall median time from identification of patients suspected for MDR-TB to the initiation of treatment was reduced from 157 days (IQR 127-200 to 38 days (IQR 30-79. This reduction was attributed mainly to a lower diagnosis time at the laboratory. Lost to follow-up rates were also significantly reduced after introduction of the LPA (12% versus 39% pre-PLA. CONCLUSION: Introduction of the LPA was associated with a major reduction in the delay between identification of patients suspected for MDR-TB and initiation of treatment, attributed mainly to a reduction in diagnostic time in the laboratory.

  11. Real-world treatment patterns and opioid use in chronic low back pain patients initiating duloxetine versus standard of care

    Directory of Open Access Journals (Sweden)

    Andrews JS

    2013-11-01

    Full Text Available Jeffrey Scott Andrews,1 Ning Wu,2 Shih-Yin Chen,2 Xia Yu,2 Xiaomei Peng,1 Diego Novick1 1Global Health Outcomes, Eli Lilly and Company, Indianapolis, IN, USA; 2Evidera, Lexington, MA, USA Abstract: To describe the use of pain medications in patients with chronic low back pain (CLBP after initiating duloxetine or standard of care (SOC [muscle relaxants, gabapentin, pregabalin, venlafaxine, and tricyclic antidepressants] for pain management, pharmacy and medical claims from Surveillance Data, Inc (SDI Health were analyzed. Adult patients with CLBP who initiated duloxetine or SOC between November 2010 and April 2011 were identified. Treatment initiation was defined as no pill coverage for duloxetine or SOC in the previous 90 days. Included patients had no opioid use in the 90 days before initiation. Propensity score matching was used to select patients with similar baseline demographic and clinical characteristics for duloxetine and SOC cohorts. Compliance with index medication was assessed via medication possession ratio (MPR and proportion of days covered (PDC for 6 months after initiation. The proportion of patients receiving opioids and days on opioids after index date were assessed, and regression models were estimated to compare opioid use between cohorts. A total of 766 patients initiated duloxetine and 6,206 patients initiated SOC. After matching, 743 patients were selected for the duloxetine (mean age 57 years; female 74% and SOC (mean age 57 years; female 75% cohorts, respectively. Of the duloxetine cohort, 92% started on or below recommended daily dose (≤60 mg. The duloxetine cohort had significantly higher MPR (0.78 versus [vs] 0.60 and PDC (0.50 vs 0.31, were less likely to use opioids (45% vs 61%, and had fewer days on opioids (median 0 vs 7 days than the SOC cohort (all P < 0.001. After adjusting for demographic and clinical characteristics, the duloxetine cohort initiated opioids later than the SOC cohort (hazard ratio 0.77, 95

  12. Initiation of triple therapy maintenance treatment among patients with COPD in the US

    OpenAIRE

    Simeone JC; Luthra R; Kaila S; Pan X; Bhagnani TD; Liu J; Wilcox TK

    2016-01-01

    Jason C Simeone,1 Rakesh Luthra,2 Shuchita Kaila,2 Xiaoyun Pan,1 Tarun D Bhagnani,1 Jieruo Liu,1 Teresa K Wilcox1 1Real-World Evidence, Evidera, Waltham, MA, 2HEOR Value Demonstration Team, Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT, USA Background: The Global Initiative for Chronic Obstructive Lung Disease (GOLD) recommends triple therapy (long-acting muscarinic receptor antagonists, long-acting beta-2 agonists, and inhaled corticosteroids) for patients with only the most s...

  13. Importance of appropriate initial antibiotic therapy and de-escalation in the treatment of nosocomial pneumonia

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    J. Rello

    2007-08-01

    Full Text Available Inappropriate initial antibiotic therapy in nosocomial pneumonia is associated with higher mortality, longer hospital stays and increased healthcare costs. The key pathogens associated with these adverse outcomes include Pseudomonas aeruginosa, methicillin-resistant Staphylococcus aureus and Acinetobacter baumannii. Due to the increasing rates of resistance, a new paradigm is needed for treating nosocomial infections in the intensive care unit (ICU. Optimal initial therapy consists of a broad-spectrum antibiotic started in a timely manner and administered at the correct dose and via the correct route. Because pathogen aetiology and resistance patterns vary from one ICU to another, recommendations for initial therapy should be tailored to each institution. Selection of the broad-spectrum antibiotic should be based on the patient's risk factors (including comorbidities, duration of ventilation and recent antibiotic exposure, suspected pathogen and up-to-date local resistance patterns. After 48–72 h, the patient should be reassessed and antibiotic therapy de-escalated based on the microbiological results and the clinical response.

  14. Optimal antiviral switching to minimize resistance risk in HIV therapy.

    Directory of Open Access Journals (Sweden)

    Rutao Luo

    Full Text Available The development of resistant strains of HIV is the most significant barrier to effective long-term treatment of HIV infection. The most common causes of resistance development are patient noncompliance and pre-existence of resistant strains. In this paper, methods of antiviral regimen switching are developed that minimize the risk of pre-existing resistant virus emerging during therapy switches necessitated by virological failure. Two distinct cases are considered; a single previous virological failure and multiple virological failures. These methods use optimal control approaches on experimentally verified mathematical models of HIV strain competition and statistical models of resistance risk. It is shown that, theoretically, order-of-magnitude reduction in risk can be achieved, and multiple previous virological failures enable greater success of these methods in reducing the risk of subsequent treatment failures.

  15. Controversies in Neurology: why monoamine oxidase B inhibitors could be a good choice for the initial treatment of Parkinson's disease

    Directory of Open Access Journals (Sweden)

    Reichmann Heinz

    2011-09-01

    Full Text Available Abstract Background Early initiation of pharmacotherapy in Parkinson's disease (PD is nowadays widely advocated by experts since the delay of treatment has shown to be associated with a significant deterioration of health related quality of life in affected patients. Due to marked advances in PD treatment during the last decades, physicians are nowadays fortunately equipped with a variety of substances that can effectively ameliorate emerging motor symptoms of the disease, among them levodopa, dopamine agonists and monoamine oxidase type B (MAO-B inhibitors. Despite numerous drug intervention trials in early PD, there is however still ongoing controversy among neurologists which substance to use for the initial treatment of the disease. Discussion In multiple studies, MAO-B inhibitors, such as selegiline and rasagiline, have shown to provide mild symptomatic effects, delay the need for levodopa, and to reduce the incidence of motor fluctuations. Although their symptomatic efficacy is inferior compared to dopamine agonists and levodopa, MAO-B inhibitors undoubtedly have fewer side effects and are easy to administer. In contrary to their competitors, MAO-B inhibitors may furthermore offer a chance for disease modification, which so far remains a major unmet need in the management of PD and eventually makes them ideal candidates for the early treatment of the disease. Summary MAO-B inhibitors may constitute a preferable therapeutic option for early PD, mainly due to their favourable safety profile and their putative neuroprotective capabilities. Since the symptomatic effects of MAO-B inhibitors are comparatively mild, dopamine agonists and levodopa should however be considered for initial treatment in those PD patients, in whom robust and immediate symptomatic relief needs to be prioritized.

  16. Readiness to adopt a performance measurement system for substance abuse treatment: Findings from the Service Quality Measures initiative

    Directory of Open Access Journals (Sweden)

    B Myers

    2017-02-01

    Full Text Available Background. A performance measurement system – the Service Quality Measures (SQM initiative – has been developed to monitor the quality of South Africa (SA’s substance abuse treatment services. Identifying factors associated with readiness to adopt this system may inform strategies to facilitate its robust implementation. Objective. To examine factors associated with readiness to adopt a performance measurement system among SA substance abuse treatment providers. Methods. We surveyed 81 treatment providers from 13 treatment sites in the Western Cape, SA. The survey examined awareness, resources, organisational climate, leadership support and readiness to adopt the SQM system. Regression analysis was used to identify factors associated with readiness to adopt this system. Results. Readiness to adopt the SQM initiative was high (M=5.64, standard deviation 1.63. In bivariate analyses, caseload size (F=3.73 (degrees of freedom (df=3.70, p=0.015, awareness (r=0.78, p<0.0001, leadership support (r=0.70, p<0.0001, resources (r=0.65, p<0.0001, openness to change (r=0.372, p=0.001, and external pressure to change were associated with readiness to adopt the SQM. In multivariate analyses, only awareness of the SQM initiative (B=0.34, standard error (SE 0.08, t=4.4, p<0.0001 and leadership support (B=0.45, SE 0.11, t=4.0, p<0.0001 were significantly associated with readiness to adopt this system. Conclusion. While treatment providers report high levels of readiness to adopt the SQM system, findings show that the likelihood of adoption can be further increased through improved provider awareness and enhanced leadership support for this health innovation.

  17. Mechanisms of Hepatitis C Viral Resistance to Direct Acting Antivirals

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    Asma Ahmed

    2015-12-01

    Full Text Available There has been a remarkable transformation in the treatment of chronic hepatitis C in recent years with the development of direct acting antiviral agents targeting virus encoded proteins important for viral replication including NS3/4A, NS5A and NS5B. These agents have shown high sustained viral response (SVR rates of more than 90% in phase 2 and phase 3 clinical trials; however, this is slightly lower in real-life cohorts. Hepatitis C virus resistant variants are seen in most patients who do not achieve SVR due to selection and outgrowth of resistant hepatitis C virus variants within a given host. These resistance associated mutations depend on the class of direct-acting antiviral drugs used and also vary between hepatitis C virus genotypes and subtypes. The understanding of these mutations has a clear clinical implication in terms of choice and combination of drugs used. In this review, we describe mechanism of action of currently available drugs and summarize clinically relevant resistance data.

  18. Anti-Viral Antibody Profiling by High Density Protein Arrays

    Science.gov (United States)

    Bian, Xiaofang; Wiktor, Peter; Kahn, Peter; Brunner, Al; Khela, Amritpal; Karthikeyan, Kailash; Barker, Kristi; Yu, Xiaobo; Magee, Mitch; Wasserfall, Clive H.; Gibson, David; Rooney, Madeleine E; Qiu, Ji; LaBaer, Joshua

    2015-01-01

    Viral infections elicit anti-viral antibodies and have been associated with various chronic diseases. Detection of these antibodies can facilitate diagnosis, treatment of infection and understanding of the mechanisms of virus associated diseases. In this work, we assayed anti-viral antibodies using a novel high density-nucleic acid programmable protein array (HD-NAPPA) platform. Individual viral proteins were expressed in situ directly from plasmids encoding proteins in an array of microscopic reaction chambers. Quality of protein display and serum response was assured by comparing intra- and inter- array correlation within or between printing batches with average correlation coefficients of 0.91 and 0.96, respectively. HD-NAPPA showed higher signal to background (S/B) ratio compared with standard NAPPA on planar glass slides and ELISA. Antibody responses to 761 antigens from 25 different viruses were profiled among patients with juvenile idiopathic arthritis (JIA) and type 1 diabetes (T1D). Common as well as unique antibody reactivity patterns were detected between patients and healthy controls. We believe HD-viral-NAPPA will enable the study of host-pathogen interactions at unprecedented dimensions and elucidate the role of pathogen infections in disease development. PMID:25758251

  19. Initial diagnosis and treatment in first-episode psychosis: can an operationalized diagnostic classification system enhance treating clinicians' diagnosis and the treatment chosen?

    LENUS (Irish Health Repository)

    Coentre, Ricardo

    2011-05-01

    Diagnosis during the initial stages of first-episode psychosis is particularly challenging but crucial in deciding on treatment. This is compounded by important differences in the two major classification systems, International Classification of Diseases, 10th revision (ICD-10) and Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV). We aimed to compare the concordance between an operationalized diagnosis using Operational Criteria Checklist (OPCRIT) and treating clinician-generated diagnosis in first episode psychosis diagnosis and its correlation with treatment prescribed.

  20. Relapse in childhood acute lymphoblastic leukemia after elective cessation of initial treatment: failure of subsequent treatment with cyclophosphamide, cytosine arabinoside, vincristine and prednisone (COAP).

    Science.gov (United States)

    Sallan, S E; Hitchcock-Bryan, S

    1981-01-01

    Although the majority of children with acute lymphoblastic leukemia (ALL) can electively stop treatment after 2 1/2-5 years of continuous disease-free remission, 20-25% of those patients relapse after discontinuation of therapy. We treated 15 patients whose disease recurred after stopping treatment. Fourteen of them attained complete remission, but the median duration of disease-free survival was only 11 months. In this population, the site of initial relapse, bone marrow or testicle, did not influence subsequent outcome. Patients who relapsed within six months of stopping initial therapy had shorter second remissions than those who relapsed after six months. We conclude that the combination chemotherapy utilized in this study was inadequate for the control of relapsed ALL. Future programs will have to use different drug combinations or bone marrow transplantation.

  1. Initiation of antipsychotic treatment by general practitioners. A case-control study

    NARCIS (Netherlands)

    Boonstra, Geartsje; Grobbee, Diederick E; Hak, Eelko; Kahn, René S; Burger, Huibert

    2011-01-01

    RATIONALE, AIMS AND OBJECTIVES: Antipsychotics are approved treatment for severe conditions and have serious side effects. Antipsychotics are often prescribed off-label. Although a substantial proportion of antipsychotics are prescribed in primary care, it is largely unknown what motivates the gener

  2. The Accelerated Intake: A Method for Increasing Initial Attendance to Outpatient Cocaine Treatment.

    Science.gov (United States)

    Festinger, David S.; And Others

    1996-01-01

    The effectiveness of offering same day appointments at an outpatient cocaine treatment program to increase intake attendance was examined. Seventy-eight clients were given standard or accelerated intake appointments. Significantly more clients who were given accelerated appointments attended the program. An accelerated intake procedure appears to…

  3. Initial feasibility and validity of a prospective memory training program in a substance use treatment population.

    Science.gov (United States)

    Sweeney, Mary M; Rass, Olga; Johnson, Patrick S; Strain, Eric C; Berry, Meredith S; Vo, Hoa T; Fishman, Marc J; Munro, Cynthia A; Rebok, George W; Mintzer, Miriam Z; Johnson, Matthew W

    2016-10-01

    Individuals with substance use disorders have shown deficits in the ability to implement future intentions, called prospective memory. Deficits in prospective memory and working memory, a critical underlying component of prospective memory, likely contribute to substance use treatment failures. Thus, improvement of prospective memory and working memory in substance use patients is an innovative target for intervention. We sought to develop a feasible and valid prospective memory training program that incorporates working memory training and may serve as a useful adjunct to substance use disorder treatment. We administered a single session of the novel prospective memory and working memory training program to participants (n = 22; 13 men, 9 women) enrolled in outpatient substance use disorder treatment and correlated performance to existing measures of prospective memory and working memory. Generally accurate prospective memory performance in a single session suggests feasibility in a substance use treatment population. However, training difficulty should be increased to avoid ceiling effects across repeated sessions. Consistent with existing literature, we observed superior performance on event-based relative to time-based prospective memory tasks. Performance on the prospective memory and working memory training components correlated with validated assessments of prospective memory and working memory, respectively. Correlations between novel memory training program performance and established measures suggest that our training engages appropriate cognitive processes. Further, differential event- and time-based prospective memory task performance suggests internal validity of our training. These data support the development of this intervention as an adjunctive therapy for substance use disorders. (PsycINFO Database Record

  4. Comparison of Video-Assisted Thoracoscopic Surgery and Intrapleural Urokinase as an Initial Treatment for Parapneumonic Effusion and Thoracic Empyema

    Directory of Open Access Journals (Sweden)

    Shungo Yukumi

    2014-05-01

    Full Text Available Introduction: The treatment of complicated parapneumonic effusion (PPE and thoracic empyema (TE is controversial; and the choice of treatment after confirming the failure of simple drainage remains unclear. The purpose of this study was to compare the outcomes of intrapleural urokinase (UK administration and video-assisted thoracoscopic surgery (VATS as initial treatment options for PPE and TE. Materials and Methods: We retrospectively reviewed and compared the data of 20 patients with PPE and TE diagnosed between January 2010 and December 2012 at our hospital, dividing them on the basis of the initial treatment into a video-assisted thoracoscopic surgery (VATS group (n=9 and UK group (n=11. Results: Age was the only statistically different parameter between both groups (P=0.025; with the mean age of the VATS and UK groups being 64 and 76 years, respectively. There was no significant difference in the duration of drainage or success rate between the UK or VATS groups. Although no statistically significant differences (P=0.20 were observed, duration of hospital stay was longer in the UK group (21 and 28 day for VATS and UK, respectively. Conclusion: VATS for PPE and TE may shorten the duration of hospital stay.However, UK administration may be used for selective patients because it is considered to yield outcomes similar to VATS.

  5. Initial treatment of complete rotator cuff tear and transition to surgical treatment: systematic review of the evidence

    Science.gov (United States)

    Abdul-Wahab, Taiceer A.; Betancourt, Jean P.; Hassan, Fadi; Thani, Saeed Al.; Choueiri, Hened; Jain, Nitin B.; Malanga, Gerard A.; Murrell, William D.; Prasad, Anil; Verborgt, Olivier

    2016-01-01

    Summary Background rotator cuff tear affects many people. Natural history, and evidence for non-operative treatment remains limited. Our objective is to assess evidence available for the efficacy and morbidity of commonly used systemic medications, physiotherapy, and injections alongside evaluating any negative long-term effects. Methods a systematic search was performed of PubMed, Cochrane, EMBASE and CINAHL dates (1 January 1960 – 1 December 2014), search terms: ‘rotator cuff tear’, ‘natural history’, ‘atraumatic’, ‘injection’, ‘physiotherapy’ or ‘physical therapy’, ‘injection’, ‘corticosteroid’, ‘PRP‘, ‘MSC’, risk of conservative treatment’, and ‘surgical indication’. Results eleven studies were included. The mean Coleman Methodology Score modified for conservative therapy is 69.21 (range 88–44) (SD 12.31). This included 2 RCTs, 7 prospective, and 2 retrospective studies. Evidence suggests it is safe to monitor symptomatic rotator cuff tears, as tear size and symptoms are not correlated with pain, function, and/or ultimate outcome. Conclusions complete rotator cuff tears may be effectively treated with injections, exercise in the short and intermediate terms respectively. Negative effect of corticosteroids on rotator cuff tissue has not been demonstrated. Timing to end conservative treatment is unknown, but likely indicated when a patient demonstrates increased weakness and loss of function not recoverable by physiotherapy. PMID:27331030

  6. An antiviral furanoquinone from Paulownia tomentosa Steud.

    Science.gov (United States)

    Kang, K H; Huh, H; Kim, B K; Lee, C K

    1999-11-01

    A methanol extract of the stem bark of Paulownia tomentosa showed antiviral activity against poliovirus types 1 and 3. Sequential liquid-liquid extraction with n-hexane, chloroform and water, and a silicagel column chromatography resulted in the purification of a compound. The compound was identified as methyl-5-hydroxy-dinaphthol[1,2-2',3']furan-7,12-dione-6-carbox yla te on the basis of spectroscopic data. The component caused a significant reduction of viral cytopathic effect when it was subjected to a standard antiviral assay by using HeLa cells. The EC(50) of the compound against poliovirus type 1 strain Brunhilde, and type 3 strain Leon were 0.3 microg/mL and 0.6 microg/mL, respectively.

  7. Characteristics and outcomes of initial virologic suppressors during analytic treatment interruption in a therapeutic HIV-1 gag vaccine trial.

    Directory of Open Access Journals (Sweden)

    Jonathan Z Li

    Full Text Available BACKGROUND: In the placebo-controlled trial ACTG A5197, a trend favoring viral suppression was seen in the HIV-1-infected subjects who received a recombinant Ad5 HIV-1 gag vaccine. OBJECTIVE: To identify individuals with initial viral suppression (plasma HIV-1 RNA set point <3.0 log(10 copies/ml during the analytic treatment interruption (ATI and evaluate the durability and correlates of virologic control and characteristics of HIV sequence evolution. METHODS: HIV-1 gag and pol RNA were amplified and sequenced from plasma obtained during the ATI. Immune responses were measured by flow cytometric analysis and intracellular cytokine expression assays. Characteristics of those with and without initial viral suppression were compared using the Wilcoxon rank sum and Fisher's exact tests. RESULTS: Eleven out of 104 participants (10.6% were classified as initial virologic suppressors, nine of whom had received the vaccine. Initial virologic suppressors had significantly less CD4+ cell decline by ATI week 16 as compared to non-suppressors (median 7 CD4+ cell gain vs. 247 CD4+ cell loss, P = 0.04. However, of the ten initial virologic suppressors with a pVL at ATI week 49, only three maintained pVL <3.0 log(10 copies/ml. HIV-1 Gag-specific CD4+ interferon-γ responses were not associated with initial virologic suppression and no evidence of vaccine-driven HIV sequence evolution was detected. Participants with initial virologic suppression were found to have a lower percentage of CD4+ CTLA-4+ cells prior to treatment interruption, but a greater proportion of HIV-1 Gag-reactive CD4+ TNF-α+ cells expressing either CTLA-4 or PD-1. CONCLUSIONS: Among individuals participating in a rAd5 therapeutic HIV-1 gag vaccine trial, initial viral suppression was found in a subset of patients, but this response was not sustained. The association between CTLA-4 and PD-1 expression on CD4+ T cells and virologic outcome warrants further study in trials of other

  8. Treatment Modalities and Antimicrobial Stewardship Initiatives in the Management of Intra-Abdominal Infections

    Science.gov (United States)

    Hoffmann, Charles; Zak, Matthew; Avery, Lisa; Brown, Jack

    2016-01-01

    Antimicrobial stewardship programs (ASPs) focus on improving the utilization of broad spectrum antibiotics to decrease the incidence of multidrug-resistant Gram positive and Gram negative pathogens. Hospital admission for both medical and surgical intra-abdominal infections (IAIs) commonly results in the empiric use of broad spectrum antibiotics such as fluoroquinolones, beta-lactam beta-lactamase inhibitors, and carbapenems that can select for resistant organisms. This review will discuss the management of uncomplicated and complicated IAIs as well as highlight stewardship initiatives focusing on the proper use of broad spectrum antibiotics. PMID:27025526

  9. Treatment Modalities and Antimicrobial Stewardship Initiatives in the Management of Intra-Abdominal Infections

    Directory of Open Access Journals (Sweden)

    Charles Hoffmann

    2016-02-01

    Full Text Available Antimicrobial stewardship programs (ASPs focus on improving the utilization of broad spectrum antibiotics to decrease the incidence of multidrug-resistant Gram positive and Gram negative pathogens. Hospital admission for both medical and surgical intra-abdominal infections (IAIs commonly results in the empiric use of broad spectrum antibiotics such as fluoroquinolones, beta-lactam beta-lactamase inhibitors, and carbapenems that can select for resistant organisms. This review will discuss the management of uncomplicated and complicated IAIs as well as highlight stewardship initiatives focusing on the proper use of broad spectrum antibiotics.

  10. Milestones in the discovery of antiviral agents: nucleosides and nucleotides

    Directory of Open Access Journals (Sweden)

    Erik de Clercq

    2012-12-01

    Full Text Available In this review article, a number of milestones in the antiviral research field on nucleosides and nucleotides are reviewed in which the author played a significant part, especially in the initial stages of their development. Highlighted are the amino acyl esters of acyclovir, particularly valacyclovir (VACV, brivudin (BVDU and the valine ester of Cf1743 (FV-100, the 2′,3′-dideoxynucleosides (nucleoside reverse transcriptase inhibitors, NRTIs, the acyclic nucleoside phosphonates (S-HPMPA, (S-HPMPC (cidofovir and alkoxyalkyl esters thereof (HDP-, ODE-CDV, adefovir and adefovir dipivoxil, tenofovir and tenofovir disoproxil fumarate (TDF, combinations containing TDF and emtricitabine, i.e., Truvada®, Atripla®, Complera®/Eviplera® and the Quad pill, and the phosphonoamidate derivatives GS-7340, GS-9131, GS-9191 and GS-9219.

  11. Identification and Analysis of Antiviral Compounds Against Poliovirus.

    Science.gov (United States)

    Leyssen, Pieter; Franco, David; Tijsma, Aloys; Lacroix, Céline; De Palma, Armando; Neyts, Johan

    2016-01-01

    The Global Polio Eradication Initiative, launched in 1988, had as its goal the eradication of polio worldwide by the year 2000 through large-scale vaccinations campaigns with the live attenuated oral PV vaccine (OPV) (Griffiths et al., Biologicals 34:73-74, 2006). Despite substantial progress, polio remains endemic in several countries and new imported cases are reported on a regular basis ( http://www.polioeradication.org/casecount.asp ).It was recognized by the poliovirus research community that developing antivirals against poliovirus would be invaluable in the post-OPV era. Here, we describe three methods essential for the identification of selective inhibitors of poliovirus replication and for determining their mode of action by time-of-drug-addition studies as well as by the isolation of compound-resistant poliovirus variants.

  12. Protective effect of creatine phosphate sodium, vitamin C combined with antiviral therapy on myocardial damage in children with viral myocarditis

    Institute of Scientific and Technical Information of China (English)

    Cai-Hong Li

    2016-01-01

    Objective:To analyze the protective effect of creatine phosphate sodium, vitamin C combined with antiviral therapy on myocardial damage in children with viral myocarditis.Methods: A total of 141 cases of children with viral myocarditis were divided into conventional treatment group (conventional antiviral therapy) and combined treatment group (creatine phosphate sodium, vitamin C combined with antiviral therapy) according to different treatment methods, and then the differences in myocardial damage markers, echocardiography parameters, inflammatory factors and oxidation/anti-oxidation indexes were compared between two groups of children after 1 course of treatment.Results: Serum myocardial damage markers IMA, CK-MB, LDH, HBDH, cTNⅠ and MYO levels as well as echocardiography parameters LAD, LVDD, RVDD, IVSD and RVOT values of combined treatment group after treatment were lower than those of conventional treatment group; serum inflammatory factors IL-10, IL-17, IL-23 and IFN-γ levels were lower than those of conventional treatment group; serum oxidation indexes NO, •OH, LPO and MDA levels were lower than those of conventional treatment group while anti-oxidation indexes SOD and SeGSH-Px levels were higher than those of conventional treatment group.Conclusion:Creatine phosphate sodium, vitamin C combined with antiviral therapy can actively protect the cardiac function of children with viral myocarditis, which is specifically related to its effect such as anti-inflammation and anti-oxidative stress.

  13. Avian Interferons and Their Antiviral Effectors

    OpenAIRE

    Santhakumar, Diwakar; Rubbenstroth, Dennis; Martinez-Sobrido, Luis; Munir, Muhammad

    2017-01-01

    Interferon (IFN) responses, mediated by a myriad of IFN-stimulated genes (ISGs), are the most profound innate immune responses against viruses. Cumulatively, these IFN effectors establish a multilayered antiviral state to safeguard the host against invading viral pathogens. Considerable genetic and functional characterizations of mammalian IFNs and their effectors have been made, and our understanding on the avian IFNs has started to expand. Similar to mammalian counterparts, three types of I...

  14. Coxsackievirus cloverleaf RNA containing a 5' triphosphate triggers an antiviral response via RIG-I activation.

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    Qian Feng

    Full Text Available Upon viral infections, pattern recognition receptors (PRRs recognize pathogen-associated molecular patterns (PAMPs and stimulate an antiviral state associated with the production of type I interferons (IFNs and inflammatory markers. Type I IFNs play crucial roles in innate antiviral responses by inducing expression of interferon-stimulated genes and by activating components of the adaptive immune system. Although pegylated IFNs have been used to treat hepatitis B and C virus infections for decades, they exert substantial side effects that limit their use. Current efforts are directed toward the use of PRR agonists as an alternative approach to elicit host antiviral responses in a manner similar to that achieved in a natural infection. RIG-I is a cytosolic PRR that recognizes 5' triphosphate (5'ppp-containing RNA ligands. Due to its ubiquitous expression profile, induction of the RIG-I pathway provides a promising platform for the development of novel antiviral agents and vaccine adjuvants. In this study, we investigated whether structured RNA elements in the genome of coxsackievirus B3 (CVB3, a picornavirus that is recognized by MDA5 during infection, could activate RIG-I when supplied with 5'ppp. We show here that a 5'ppp-containing cloverleaf (CL RNA structure is a potent RIG-I inducer that elicits an extensive antiviral response that includes induction of classical interferon-stimulated genes, as well as type III IFNs and proinflammatory cytokines and chemokines. In addition, we show that prophylactic treatment with CVB3 CL provides protection against various viral infections including dengue virus, vesicular stomatitis virus and enterovirus 71, demonstrating the antiviral efficacy of this RNA ligand.

  15. RNA interference and antiviral therapy

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    RNA interference (RNAi) is an evolutionally conserved gene silencing mechanism present in a variety of eukaryotic species. RNAi uses short double-stranded RNA (dsRNA) to trigger degradation or translation repression of homologous RNA targets in a sequence-specific manner. This system can be induced effectively in vitro and in vivo by direct application of small interfering RNAs (siRNAs), or by expression of short hairpin RNA (shRNA) with non-viral and viral vectors. To date, RNAi has been extensively used as a novel and effective tool for functional genomic studies, and has displayed great potential in treating human diseases, including human genetic and acquired disorders such as cancer and viral infections. In the present review, we focus on the recent development in the use of RNAi in the prevention and treatment of viral infections. The mechanisms,strategies, hurdles and prospects of employing RNAi in the pharmaceutical industry are also discussed.

  16. Meeting report: 4th ISIRV antiviral group conference: Novel antiviral therapies for influenza and other respiratory viruses.

    Science.gov (United States)

    McKimm-Breschkin, Jennifer L; Fry, Alicia M

    2016-05-01

    The International Society for Influenza and other Respiratory Virus Diseases (isirv) held its 4th Antiviral Group Conference at the University of Texas on 2-4 June, 2015. With emerging resistance to the drugs currently licensed for treatment and prophylaxis of influenza viruses, primarily the neuraminidase inhibitor oseltamivir phosphate (Tamiflu) and the M2 inhibitors amantadine and rimantadine, and the lack of effective interventions against other respiratory viruses, the 3-day programme focused on the discovery and development of inhibitors of several virus targets and key host cell factors involved in virus replication or mediating the inflammatory response. Virus targets included the influenza haemagglutinin, neuraminidase and M2 proteins, and both the respiratory syncytial virus and influenza polymerases and nucleoproteins. Therapies for rhinoviruses and MERS and SARS coronaviruses were also discussed. With the emerging development of monoclonal antibodies as therapeutics, the potential implications of antibody-dependent enhancement of disease were also addressed. Topics covered all aspects from structural and molecular biology to preclinical and clinical studies. The importance of suitable clinical trial endpoints and regulatory issues were also discussed from the perspectives of both industry and government. This meeting summary provides an overview, not only for the conference participants, but also for those interested in the current status of antivirals for respiratory viruses.

  17. Systemic corticosteroids and early administration of antiviral agents for pneumonia with acute wheezing due to influenza A(H1N1pdm09 in Japan.

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    Koichiro Kudo

    Full Text Available BACKGROUND: Pneumonia patients with wheezing due to influenza A(H1N1pdm09 were frequently treated with systemic corticosteroids in Japan although systemic corticosteroid for critically ill patients with pneumonia caused by influenza A(H1N1pdm09 has been controversial. Applicability of systemic corticosteroid treatment needs to be evaluated. METHODS/PRINCIPAL FINDINGS: We retrospectively reviewed 89 subjects who were diagnosed with influenza A(H1N1pdm09 and admitted to a national hospital, Tokyo during the pandemic period. The median age of subjects (45 males was 8 years (range, 0-71. All subjects were treated with antiviral agents and the median time from symptom onset to initiation of antiviral agents was 2 days (range, 0-7. Subjects were classified into four groups: upper respiratory tract infection, wheezing illness, pneumonia with wheezing, and pneumonia without wheezing. The characteristics of each group was evaluated. A history of asthma was found more frequently in the wheezing illness (55.6% and pneumonia with wheezing (43.3% groups than in the other two groups (p = 0.017. Corticosteroid treatment was assessed among subjects with pneumonia. Oxygen saturation was lower in subjects receiving corticosteroids (steroid group than in subjects not receiving corticosteroids (no-steroid group (p<0.001. The steroid group required greater oxygen supply than the no-steroid group (p<0.001. No significant difference was found by the Kaplan-Meier method between the steroid and the no-steroid groups in hours to fever alleviation from the initiation of antiviral agents and hospitalization days. In logistic regression analysis, wheezing, pneumonia and oxygen saturation were independent factors associated with using systemic corticosteroids. CONCLUSION: Patients with wheezing and a history of asthma were frequently found in the study subjects. Systemic corticosteroids together with early administration of antiviral agents to pneumonia with wheezing and

  18. Antiviral biflavonoids from Radix Wikstroemiae (Liaogewanggen

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    Ye Wencai

    2010-06-01

    Full Text Available Abstract Background Radix Wikstroemiae is a common Chinese herbal medicine. The ethyl acetate fraction of the ethanolic extract of W. indica possesses potent in vitro antiviral activity against respiratory syncytial virus (RSV. This study aims to identify the antiviral components of the active fraction. Methods The active fraction of the Radix Wikstroemiae extract was isolated with chromatographic methods such as silica gel, Sephadex LH-20 and semi-preparative high performance liquid chromatography (HPLC columns. The structures of the isolated compounds were determined based on spectroscopic analyses. The in vitro antiviral activity of the compounds against RSV was tested with the cytopathic effect (CPE reduction assay and the 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT method. Results Four biflavonoids, namely neochamaejasmin B, genkwanol B, genkwanol C and stelleranol, were isolated and characterized. Genkwanol B, genkwanol C and stelleranol, which are stereo isomers of spirobiflavonoids, showed potent anti-RSV activity whereas neochamaejasmin B did not. Conclusion Neochamaejasmin B, genkwanol B, genkwanol C and stelleranol were isolated from Radix Wikstroemiae and the complete absolute configurations of five chiral carbons in stelleranol were substantiated for the first time. Furthermore, the anti-RSV activity of genkwanol B, genkwanol C and stelleranol was reported for the first time.

  19. Synaptic transmission and the susceptibility of HIV infection to anti-viral drugs

    Science.gov (United States)

    Komarova, Natalia L.; Levy, David N.; Wodarz, Dominik

    2013-07-01

    Cell-to-cell viral transmission via virological synapses has been argued to reduce susceptibility of the virus population to anti-viral drugs through multiple infection of cells, contributing to low-level viral persistence during therapy. Using a mathematical framework, we examine the role of synaptic transmission in treatment susceptibility. A key factor is the relative probability of individual virions to infect a cell during free-virus and synaptic transmission, a currently unknown quantity. If this infection probability is higher for free-virus transmission, then treatment susceptibility is lowest if one virus is transferred per synapse, and multiple infection of cells increases susceptibility. In the opposite case, treatment susceptibility is minimized for an intermediate number of virions transferred per synapse. Hence, multiple infection via synapses does not simply lower treatment susceptibility. Without further experimental investigations, one cannot conclude that synaptic transmission provides an additional mechanism for the virus to persist at low levels during anti-viral therapy.

  20. Cervical mature teratoma 17 years after initial treatment of testicular teratocarcinoma: report of a late relapse

    Directory of Open Access Journals (Sweden)

    Alavion Mina

    2007-01-01

    Full Text Available Abstract Background Late relapses of testicular germ cell tumor are uncommon. We report a case of cervical mature teratoma appeared 17 years after treatment of testicular teratocarcinoma. Case presentation A 20- year- old patient underwent left sided orchiectomy followed by systemic therapy and retroperitoneal residual mass resection in 1989. He remained in complete remission for 200 months. In 2005 a huge left supraclavicular neck mass with extension to anterior mediastinum appeared. Radical surgical resection of the mass was performed and pathologic examination revealed mature teratoma. Conclusion This is one of the longest long-term reported intervals of a mature teratoma after treatment of a testicular nonseminoma germ cell tumor. This case emphasizes the necessity for follow up of testicular cancer throughout the patient's life.

  1. Bimaxillary Advancement as the Initial Treatment of Obstructive Sleep Apnea: Five Years Follow-Up of the Pori Experience

    Directory of Open Access Journals (Sweden)

    Antti Raunio

    2012-03-01

    Full Text Available Objectives: Bimaxillary advancement surgery has proven to be effective treatment of obstructive sleep apnea syndrome. According to the Stanford protocol upper airway soft tissue surgery or advancement of tongue by chin plastic surgery is first carried out and if obstructive sleep apnea persists, then bimaxillary advancement is done. This study describes the 5 year outcome of 13 obstructive sleep apnea patients in whom the Stanford protocol was omitted and bimaxillary advancement was carried out as initial surgical treatment. Material and Methods: Patients were divided in two groups. Group A comprised patients with obstructive sleep apnea (OSAS confirmed by polysomnography in whom ODI-4 (oxygen desaturation index was 5 or more. Group B consisted of patients with occlusal problems needing orthognathic surgery and with OSAS symptoms but no clear disease on polysomnography, where the ODI-4 index was less than 5. Both groups were treated with bimaxillary advancement surgery (BAS as initial therapy. Results: In the group A mean ODI-4 was 17.8 (SD 12 before treatment and 3.5 (SD 3.4 at 5-year follow-up (P = 0.018 in paired differences t-test. In group B the ODI-4 remained below 5. In group A mean saturation improved from 94.3% (SD 1.6 to 96.3% (SD 2, P = 0.115 and in group B from 96.3% (SD 1.2 to 97.8% (SD 1.7, P = 0.056 (in paired differences t-test. The static charge sensitive bed evaluation showed improvement in all patients except one. Conclusions: Bimaxillary advancement surgery is safe and reliable as an initial surgical treatment of obstructive sleep apnea syndrome.

  2. Multi-dimensional Treatment Foster Care in England: differential effects by level of initial antisocial behaviour.

    Science.gov (United States)

    Sinclair, Ian; Parry, Elizabeth; Biehal, Nina; Fresen, John; Kay, Catherine; Scott, Stephen; Green, Jonathan

    2016-08-01

    Multi-dimensional Treatment Foster Care (MTFC), recently renamed Treatment Foster Care Oregon for Adolescents (TFCO-A) is an internationally recognised intervention for troubled young people in public care. This paper seeks to explain conflicting results with MTFC by testing the hypotheses that it benefits antisocial young people more than others and does so through its effects on their behaviour. Hard-to-manage young people in English foster or residential homes were assessed at entry to a randomised and case-controlled trial of MTFC (n = 88) and usual care (TAU) (n = 83). Primary outcome was the Children's Global Assessment Scale (CGAS) at 12 months analysed according to high (n = 112) or low (n = 59) baseline level of antisocial behaviour on the Health of the Nation Outcome Scales for Children and Adolescents. After adjusting for covariates, there was no overall treatment effect on CGAS. However, the High Antisocial Group receiving MTFC gained more on the CGAS than the Low group (mean improvement 9.36 points vs. 5.33 points). This difference remained significant (p antisocial behaviour ratings in MTFC. These analyses support the use of MTFC for youth in public care but only for those with higher levels of antisocial behaviour. Further work is needed on whether such benefits persist, and on possible negative effects of this treatment for those with low antisocial behaviour.Trial Registry Name: ISRCTNRegistry identification number: ISRCTN 68038570Registry URL: www.isrctn.com.

  3. Yield Responses of Black Spruce to Forest Vegetation Management Treatments: Initial Responses and Rotational Projections

    Directory of Open Access Journals (Sweden)

    Peter F. Newton

    2012-01-01

    Full Text Available The objectives of this study were to (1 quantitatively summarize the early yield responses of black spruce (Picea mariana (Mill. B.S.P. to forest vegetation management (FVM treatments through a meta-analytical review of the scientific literature, and (2 given (1, estimate the rotational consequences of these responses through model simulation. Based on a fixed-effects meta-analytic approach using 44 treated-control yield pairs derived from 12 experiments situated throughout the Great Lakes—St. Lawrence and Canadian Boreal Forest Regions, the resultant mean effect size (response ratio and associated 95% confidence interval for basal diameter, total height, stem volume, and survival responses, were respectively: 54.7% (95% confidence limits (lower/upper: 34.8/77.6, 27.3% (15.7/40.0, 198.7% (70.3/423.5, and 2.9% (−5.5/11.8. The results also indicated that early and repeated treatments will yield the largest gains in terms of mean tree size and survival. Rotational simulations indicated that FVM treatments resulted in gains in stand-level operability (e.g., reductions of 9 and 5 yr for plantations established on poor-medium and good-excellent site qualities, resp.. The challenge of maintaining coniferous forest cover on recently disturbed sites, attaining statutory-defined free-to-grow status, and ensuring long-term productivity, suggest that FVM will continue to be an essential silvicultural treatment option when managing black spruce plantations.

  4. Initial evaluation, diagnosis, and treatment of anorexia nervosa and bulimia nervosa.

    Science.gov (United States)

    Harrington, Brian C; Jimerson, Michelle; Haxton, Christina; Jimerson, David C

    2015-01-01

    Eating disorders are life-threatening conditions that are challenging to address; however, the primary care setting provides an important opportunity for critical medical and psychosocial intervention. The recently published Diagnostic and Statistical Manual of Mental Disorders, 5th ed., includes updated diagnostic criteria for anorexia nervosa (e.g., elimination of amenorrhea as a diagnostic criterion) and for bulimia nervosa (e.g., criterion for frequency of binge episodes decreased to an average of once per week). In addition to the role of environmental triggers and societal expectations of body size and shape, research has suggested that genes and discrete biochemical signals contribute to the development of eating disorders. Anorexia nervosa and bulimia nervosa occur most often in adolescent females and are often accompanied by depression and other comorbid psychiatric disorders. For low-weight patients with anorexia nervosa, virtually all physiologic systems are affected, ranging from hypotension and osteopenia to life-threatening arrhythmias, often requiring emergent assessment and hospitalization for metabolic stabilization. In patients with frequent purging or laxative abuse, the presence of electrolyte abnormalities requires prompt intervention. Family-based treatment is helpful for adolescents with anorexia nervosa, whereas short-term psychotherapy, such as cognitive behavior therapy, is effective for most patients with bulimia nervosa. The use of psychotropic medications is limited for anorexia nervosa, whereas treatment studies have shown a benefit of antidepressant medications for patients with bulimia nervosa. Treatment is most effective when it includes a multidisciplinary, teambased approach.

  5. Treatment Result in the Initial Stage of Kanazawa Mobile Embolectomy Team for Acute Ischemic Stroke

    Science.gov (United States)

    UCHIYAMA, Naoyuki; MISAKI, Kouichi; MOHRI, Masanao; KAMIDE, Tomoya; HIROTA, Yuichi; HIGASHI, Ryo; MINAMIDE, Hisato; KOHDA, Yukihiko; ASAHI, Takashi; SHOIN, Katsuo; IWATO, Masayuki; KITA, Daisuke; HAMADA, Yoshitaka; YOSHIDA, Yuya; NAKADA, Mitsutoshi

    2016-01-01

    Five recent multicenter randomized controlled trials (RCTs) have clearly shown the superiority of mechanical thrombectomy in large vessel occlusion acute ischemic stroke compared to systemic thrombolysis. Although 14 hospitals in Ishikawa prefecture have uninterrupted availability of systemic thrombolysis, mechanical thrombectomy is not available at all of these hospitals. Therefore, we established a Kanazawa mobile embolectomy team (KMET), which could travel to these hospitals and perform the acute reperfusion therapy. In this article, we report early treatment outcomes and validate the effectiveness of a network between affiliated hospitals and KMET. Between January 2014 and December 2015, 48 patients, aged 45–92 years (mean: 73.0 years), underwent acute reperfusion therapy provided by KMET in 10 affiliated hospitals of Kanazawa University Hospital. The pre-treatment NIHSS scores ranged from 5 to 39 (mean: 19.1). ASPECTS+W ranged from 1 to 11 (mean: 7.3). Successful revascularization, defined as thrombolysis in cerebral infarction (TICI) 2b or 3, was achieved in 38/48 cases (80%), and a good outcome, defined as modified Rankin Scale (mRS) score from 0 to 2 at 90 days after the treatment, was achieved in 24/48 cases (50%). There were two cases of intracranial bleeding (4%). Mean time from onset to recanalization was 297 min. These results, which are similar to those of five previous RCTs, suggest that a collaborative network between affiliated hospitals and KMET is effective for acute reperfusion therapy in local areas wherein experienced neuroendovascular specialists are insufficient. PMID:27725522

  6. A preliminary model of work during initial examination and treatment planning appointments.

    Science.gov (United States)

    Irwin, J Y; Torres-Urquidy, M H; Schleyer, T; Monaco, V

    2009-01-10

    Objective This study's objective was to formally describe the work process for charting and treatment planning in general dental practice to inform the design of a new clinical computing environment.Methods Using a process called contextual inquiry, researchers observed 23 comprehensive examination and treatment planning sessions during 14 visits to 12 general US dental offices. For each visit, field notes were analysed and reformulated as formalised models. Subsequently, each model type was consolidated across all offices and visits. Interruptions to the workflow, called breakdowns, were identified.Results Clinical work during dental examination and treatment planning appointments is a highly collaborative activity involving dentists, hygienists and assistants. Personnel with multiple overlapping roles complete complex multi-step tasks supported by a large and varied collection of equipment, artifacts and technology. Most of the breakdowns were related to technology which interrupted the workflow, caused rework and increased the number of steps in work processes.Conclusion Current dental software could be significantly improved with regard to its support for communication and collaboration, workflow, information design and presentation, information content, and data entry.

  7. Tannic acid modified silver nanoparticles show antiviral activity in herpes simplex virus type 2 infection.

    Directory of Open Access Journals (Sweden)

    Piotr Orlowski

    Full Text Available The interaction between silver nanoparticles and herpesviruses is attracting great interest due to their antiviral activity and possibility to use as microbicides for oral and anogenital herpes. In this work, we demonstrate that tannic acid modified silver nanoparticles sized 13 nm, 33 nm and 46 nm are capable of reducing HSV-2 infectivity both in vitro and in vivo. The antiviral activity of tannic acid modified silver nanoparticles was size-related, required direct interaction and blocked virus attachment, penetration and further spread. All tested tannic acid modified silver nanoparticles reduced both infection and inflammatory reaction in the mouse model of HSV-2 infection when used at infection or for a post-infection treatment. Smaller-sized nanoparticles induced production of cytokines and chemokines important for anti-viral response. The corresponding control buffers with tannic acid showed inferior antiviral effects in vitro and were ineffective in blocking in vivo infection. Our results show that tannic acid modified silver nanoparticles are good candidates for microbicides used in treatment of herpesvirus infections.

  8. A Quest for Initiating Cells of Head and Neck Cancer and Their Treatment

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Chao [Department of Otolaryngology and Head and Neck Surgery Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, 12200 Berlin (Germany); Department of Head and Neck Surgery, Zhejiang Cancer Hospital (China); Köberle, Beate [Institute of Toxicology, University Medical Center, Mainz (Germany); Kaufmann, Andreas M. [Clinic for Gynecology, Charité-Universitätsmedizin Berlin, Berlin (Germany); Albers, Andreas E., E-mail: andreas.albers@charite.de [Department of Otolaryngology and Head and Neck Surgery Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, 12200 Berlin (Germany)

    2010-07-27

    The biology of head and neck squamous cell carcinomas (HNSCC) and other cancers have been related to cancer stem-like cells (CSC). Specific markers, which vary considerably depending on tumor type or tissue of origin, characterize CSC. CSC are cancer initiating, sustaining and mostly quiescent. Compared to bulk tumors, CSC are less sensitive to chemo- and radiotherapy and may have low immunogenicity. Therapeutic targeting of CSC may improve clinical outcome. HNSCC has two main etiologies: human papillomavirus, a virus infecting epithelial stem cells, and tobacco and alcohol abuse. Here, current knowledge of HNSCC-CSC biology is reviewed and parallels to CSC of other origin are drawn where necessary for a comprehensive picture.

  9. Robotic pulmonary lobectomy for lung cancer treatment: program implementation and initial experience

    Directory of Open Access Journals (Sweden)

    Ricardo Mingarini Terra

    Full Text Available ABSTRACT Objective: To describe the implementation of a robotic thoracic surgery program at a public tertiary teaching hospital and to analyze its initial results. Methods: This was a planned interim analysis of a randomized clinical trial aimed at comparing video-assisted thoracoscopic surgery and robotic surgery in terms of the results obtained after pulmonary lobectomy. The robotic surgery program developed at the Instituto do Câncer do Estado de São Paulo, in the city of São Paulo, Brazil, is a multidisciplinary initiative involving various surgical specialties, as well as anesthesiology, nursing, and clinical engineering teams. In this analysis, we evaluated the patients included in the robotic lobectomy arm of the trial during its first three months (from April to June of 2015. Results: Ten patients were included in this analysis. There were eight women and two men. The mean age was 65.1 years. All of the patients presented with peripheral tumors. We performed right upper lobectomy in four patients, right lower lobectomy in four, and left upper lobectomy in two. Surgical time varied considerably (range, 135-435 min. Conversion to open surgery or video-assisted thoracoscopic surgery was not necessary in any of the cases. Intraoperative complications were not found. Only the first patient required postoperative transfer to the ICU. There were no deaths or readmissions within the first 30 days after discharge. The only postoperative complication was chest pain (grade 3, in two patients. Pathological examination revealed complete tumor resection in all cases. Conclusions: When there is integration and proper training of all of the teams involved, the implementation of a robotic thoracic surgery program is feasible and can reduce morbidity and mortality.

  10. Drug–drug interactions during antiviral therapy for chronic hepatitis C

    OpenAIRE

    Kiser, Jennifer J.; Burton, James R.; Everson, Gregory T.

    2013-01-01

    The emergence of direct-acting antiviral agents (DAAs) for HCV infection represents a major advance in treatment. The NS3 protease inhibitors, boceprevir and telaprevir, were the first DAAs to receive regulatory approval. When combined with PEG-IFN and ribavirin, these agents increase rates of sustained virologic response in HCV genotype 1 to ~70%. However, this treatment regimen is associated with several toxicities. In addition, both boceprevir and telaprevir are substrates for and inhibito...

  11. TU-A-BRD-01: Outcomes of Hypofractionated Treatments - Initial Results of the WGSBRT

    Energy Technology Data Exchange (ETDEWEB)

    Li, X [Medical College of Wisconsin, Milwaukee, WI (United States); Lee, P [UCLA, Los Angeles, CA (United States); Ohri, N [Albert Einstein College of Medicine, Bronx, NY (United States); Joiner, M [Wayne State University, Detroit, MI (United States); Kong, F [Georgia Regents University, Augusta, GA (Georgia); Jackson, A [Mem Sloan-Kettering Cancer Ctr, New York, NY (United States)

    2014-06-15

    Stereotactic Body Radiation Therapy (SBRT) has emerged in recent decades as a treatment paradigm that is becoming increasingly important in clinical practice. Clinical outcomes data are rapidly accumulating. Although published relations between outcomes and dose distributions are still sparse, the field has progressed to the point where evidence-based normal tissue dose-volume constraints, prescription strategies, and Tumor Control Probability (TCP) and Normal Tissue Complication Probability (NTCP) models can be developed. The Working Group on SBRT (WGSBRT), under the Biological Effects Subcommittee of AAPM, is a group of physicists and physicians working in the area of SBRT. It is currently performing critical literature reviews to extract and synthesize usable data and to develop guidelines and models to aid with safe and effective treatment. The group is investigating clinically relevant findings from SBRT in six anatomical regions: Cranial, Head and Neck, Thoracic, Abdominal, Pelvic, and Spinal. In this session of AAPM 2014, interim results are presented on TCP for lung and liver, NTCP for thoracic organs, and radiobiological foundations:• Lung TCP: Detailed modeling of TCP data from 118 published studies on early stage lung SBRT investigates dose response and hypothesized mechanisms to explain the improved outcomes of SBRT. This is presented from the perspective of a physicist, a physician, and a radiobiologist.• Liver TCP: For primary and metastatic liver tumors, individual patient data were extracted from published reports to examine the effects of biologically effective dose on local control.• Thoracic NTCP: Clinically significant SBRT toxicity of lung, rib / chest wall and other structures are evaluated and compared among published clinical data, in terms of risk, risk factors, and safe practice.• Improving the clinical utility of published toxicity reports from SBRT and Hypofractionated treatments. What do we want, and how do we get it? Methods

  12. Ribonuclease, deoxyribonuclease, and antiviral activity of Escherichia coli-expressed Bougainvillea xbuttiana antiviral protein 1.

    Science.gov (United States)

    Choudhary, N L; Yadav, O P; Lodha, M L

    2008-03-01

    A full-length cDNA encoding ribosome-inactivating/antiviral protein from the leaves of Bougainvillea xbuttiana was recently isolated. The coding region of cDNA was cloned and expressed in Escherichia coli, and the protein product was designated as BBAP1 (Bougainvillea xbuttiana antiviral protein 1). BBAP1 showed ribonuclease activity against Torula yeast RNA. It also exhibited depurination activity against supercoiled pBlueScript SK+ plasmid DNA in a concentration dependent manner, and was found to convert nicked circular DNA into linear form only at higher concentration. On bioassay, BBAP1 exhibited antiviral activity against sunnhemp rosette virus infecting Cyamopsis tetragonoloba leaves in which 95% inhibition of local lesion formation was observed.

  13. Thyroglobulin fluctuations in patients with iodine-refractory differentiated thyroid carcinoma on lenvatinib treatmentinitial experience

    Science.gov (United States)

    Werner, R. A.; Lückerath, K.; Schmid, J. S.; Higuchi, T.; Kreissl, M. C.; Grelle, I.; Reiners, C.; Buck, A. K.; Lapa, C.

    2016-01-01

    Tyrosine kinase inhibitors (TKI) have shown clinical effectiveness in iodine-refractory differentiated thyroid cancer (DTC). The corresponding role of serum thyroglobulin (Tg) in iodine-refractory DTC has not been investigated yet. 9 patients (3 female, 61 ± 8y) with progressive iodine-refractory DTC starting on lenvatinib were considered. Tumor restaging was performed every 2–3 months including contrast-enhanced computed tomography (CT, RECIST 1.1). Serum Tg was measured and compared to imaging findings. After treatment initiation, serum Tg levels dropped in all patients with a median reduction of 86.2%. During long-term follow-up (median, 25.2 months), fluctuations in Tg could be observed in 8/9 subjects. According to RECIST, 6/9 subjects achieved a partial response or stable disease with the remaining 3/9 experiencing progressive disease (2/3 with Tg levels rising above baseline). All of the patients with disease progression presented with a preceding continuous rise in serum Tg, whereas tumor marker oscillations in the subjects with controlled disease were only intermittent. Initiation of lenvatinib in iodine-refractory DTC patients is associated with a significant reduction in serum Tg levels as a marker of treatment response. In the course of treatment, transient Tg oscillations are a frequent phenomenon that may not necessarily reflect morphologic tumor progression. PMID:27306607

  14. Integrative Genomics-Based Discovery of Novel Regulators of the Innate Antiviral Response.

    Science.gov (United States)

    van der Lee, Robin; Feng, Qian; Langereis, Martijn A; Ter Horst, Rob; Szklarczyk, Radek; Netea, Mihai G; Andeweg, Arno C; van Kuppeveld, Frank J M; Huynen, Martijn A

    2015-10-01

    The RIG-I-like receptor (RLR) pathway is essential for detecting cytosolic viral RNA to trigger the production of type I interferons (IFNα/β) that initiate an innate antiviral response. Through systematic assessment of a wide variety of genomics data, we discovered 10 molecular signatures of known RLR pathway components that collectively predict novel members. We demonstrate that RLR pathway genes, among others, tend to evolve rapidly, interact with viral proteins, contain a limited set of protein domains, are regulated by specific transcription factors, and form a tightly connected interaction network. Using a Bayesian approach to integrate these signatures, we propose likely novel RLR regulators. RNAi knockdown experiments revealed a high prediction accuracy, identifying 94 genes among 187 candidates tested (~50%) that affected viral RNA-induced production of IFNβ. The discovered antiviral regulators may participate in a wide range of processes that highlight the complexity of antiviral defense (e.g. MAP3K11, CDK11B, PSMA3, TRIM14, HSPA9B, CDC37, NUP98, G3BP1), and include uncharacterized factors (DDX17, C6orf58, C16orf57, PKN2, SNW1). Our validated RLR pathway list (http://rlr.cmbi.umcn.nl/), obtained using a combination of integrative genomics and experiments, is a new resource for innate antiviral immunity research.

  15. Integrative Genomics-Based Discovery of Novel Regulators of the Innate Antiviral Response.

    Directory of Open Access Journals (Sweden)

    Robin van der Lee

    2015-10-01

    Full Text Available The RIG-I-like receptor (RLR pathway is essential for detecting cytosolic viral RNA to trigger the production of type I interferons (IFNα/β that initiate an innate antiviral response. Through systematic assessment of a wide variety of genomics data, we discovered 10 molecular signatures of known RLR pathway components that collectively predict novel members. We demonstrate that RLR pathway genes, among others, tend to evolve rapidly, interact with viral proteins, contain a limited set of protein domains, are regulated by specific transcription factors, and form a tightly connected interaction network. Using a Bayesian approach to integrate these signatures, we propose likely novel RLR regulators. RNAi knockdown experiments revealed a high prediction accuracy, identifying 94 genes among 187 candidates tested (~50% that affected viral RNA-induced production of IFNβ. The discovered antiviral regulators may participate in a wide range of processes that highlight the complexity of antiviral defense (e.g. MAP3K11, CDK11B, PSMA3, TRIM14, HSPA9B, CDC37, NUP98, G3BP1, and include uncharacterized factors (DDX17, C6orf58, C16orf57, PKN2, SNW1. Our validated RLR pathway list (http://rlr.cmbi.umcn.nl/, obtained using a combination of integrative genomics and experiments, is a new resource for innate antiviral immunity research.

  16. The impact of pathological narcissism on psychotherapy utilization, initial symptom severity, and early-treatment symptom change: a naturalistic investigation.

    Science.gov (United States)

    Ellison, William D; Levy, Kenneth N; Cain, Nicole M; Ansell, Emily B; Pincus, Aaron L

    2013-01-01

    The impact of pathological narcissism on psychotherapy has seldom been investigated empirically, despite extensive clinical theory proposing that highly narcissistic individuals should be reluctant to engage in treatment and derive smaller benefits from therapy. In this study, we investigate the relationship between scores on the Pathological Narcissism Inventory (PNI; Pincus et al., 2009), which assesses both narcissistic grandiosity and narcissistic vulnerability, and clinical variables in a sample of outpatients (N=60) at a community mental health center. Results indicated that grandiosity, but not vulnerability, was negatively related to the use of adjunctive services and positively predicted client-initiated termination of psychotherapy. In addition, grandiosity and vulnerability were related to initial levels of different symptoms in multilevel models using a subsample (n=41) but not generally related to the linear rate of symptom change in early psychotherapy. The results highlight the clinical utility of assessing pathological narcissism in a real-world psychotherapeutic context.

  17. Initiation of triple therapy maintenance treatment among patients with COPD in the US

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    Simeone JC

    2016-12-01

    Full Text Available Jason C Simeone,1 Rakesh Luthra,2 Shuchita Kaila,2 Xiaoyun Pan,1 Tarun D Bhagnani,1 Jieruo Liu,1 Teresa K Wilcox1 1Real-World Evidence, Evidera, Waltham, MA, 2HEOR Value Demonstration Team, Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT, USA Background: The Global Initiative for Chronic Obstructive Lung Disease (GOLD recommends triple therapy (long-acting muscarinic receptor antagonists, long-acting beta-2 agonists, and inhaled corticosteroids for patients with only the most severe COPD. Data on the proportion of COPD patients on triple therapy and their characteristics are sparse and dated. Objective 1 of this study was to estimate the proportion of all, and all treated, COPD patients receiving triple therapy. Objective 2 was to characterize those on triple therapy and assess the concordance of triple therapy use with GOLD guidelines. Patients and methods: This retrospective study used claims from the IMS PharMetrics Plus database from 2009 to 2013. Cohort 1 was selected to assess Objective 1 only; descriptive analyses were conducted in Cohort 2 to answer Objective 2. A validated claims-based algorithm and severity and frequency of exacerbations were used as proxies for COPD severity. Results: Of all 199,678 patients with COPD in Cohort 1, 7.5% received triple therapy after diagnosis, and 25.5% of all treated patients received triple therapy. In Cohort 2, 30,493 COPD patients (mean age =64.7 years who initiated triple therapy were identified. Using the claims-based algorithm, 34.5% of Cohort 2 patients were classified as having mild disease (GOLD 1, 40.8% moderate (GOLD 2, 22.5% severe (GOLD 3, and 2.3% very severe (GOLD 4. Using exacerbation severity and frequency, 60.6% of patients were classified as GOLD 1/2 and 39.4% as GOLD 3/4. Conclusion: In this large US claims database study, one-quarter of all treated COPD patients received triple therapy. Although triple therapy is recommended for the most severe COPD patients

  18. Initiation of triple therapy maintenance treatment among patients with COPD in the US

    Science.gov (United States)

    Simeone, Jason C; Luthra, Rakesh; Kaila, Shuchita; Pan, Xiaoyun; Bhagnani, Tarun D; Liu, Jieruo; Wilcox, Teresa K

    2017-01-01

    Background The Global Initiative for Chronic Obstructive Lung Disease (GOLD) recommends triple therapy (long-acting muscarinic receptor antagonists, long-acting beta-2 agonists, and inhaled corticosteroids) for patients with only the most severe COPD. Data on the proportion of COPD patients on triple therapy and their characteristics are sparse and dated. Objective 1 of this study was to estimate the proportion of all, and all treated, COPD patients receiving triple therapy. Objective 2 was to characterize those on triple therapy and assess the concordance of triple therapy use with GOLD guidelines. Patients and methods This retrospective study used claims from the IMS PharMetrics Plus database from 2009 to 2013. Cohort 1 was selected to assess Objective 1 only; descriptive analyses were conducted in Cohort 2 to answer Objective 2. A validated claims-based algorithm and severity and frequency of exacerbations were used as proxies for COPD severity. Results Of all 199,678 patients with COPD in Cohort 1, 7.5% received triple therapy after diagnosis, and 25.5% of all treated patients received triple therapy. In Cohort 2, 30,493 COPD patients (mean age =64.7 years) who initiated triple therapy were identified. Using the claims-based algorithm, 34.5% of Cohort 2 patients were classified as having mild disease (GOLD 1), 40.8% moderate (GOLD 2), 22.5% severe (GOLD 3), and 2.3% very severe (GOLD 4). Using exacerbation severity and frequency, 60.6% of patients were classified as GOLD 1/2 and 39.4% as GOLD 3/4. Conclusion In this large US claims database study, one-quarter of all treated COPD patients received triple therapy. Although triple therapy is recommended for the most severe COPD patients, spirometry is infrequently assessed, and a majority of the patients who receive triple therapy may have only mild/moderate disease. Any potential overprescribing of triple therapy may lead to unnecessary costs to the patient and health care system. PMID:28053518

  19. Antiviral immunity of Anopheles gambiae is highly compartmentalized, with distinct roles for RNA interference and gut microbiota.

    Science.gov (United States)

    Carissimo, Guillaume; Pondeville, Emilie; McFarlane, Melanie; Dietrich, Isabelle; Mitri, Christian; Bischoff, Emmanuel; Antoniewski, Christophe; Bourgouin, Catherine; Failloux, Anna-Bella; Kohl, Alain; Vernick, Kenneth D

    2015-01-13

    Arboviruses are transmitted by mosquitoes and other arthropods to humans and animals. The risk associated with these viruses is increasing worldwide, including new emergence in Europe and the Americas. Anopheline mosquitoes are vectors of human malaria but are believed to transmit one known arbovirus, o'nyong-nyong virus, whereas Aedes mosquitoes transmit many. Anopheles interactions with viruses have been little studied, and the initial antiviral response in the midgut has not been examined. Here, we determine the antiviral immune pathways of the Anopheles gambiae midgut, the initial site of viral infection after an infective blood meal. We compare them with the responses of the post-midgut systemic compartment, which is the site of the subsequent disseminated viral infection. Normal viral infection of the midgut requires bacterial flora and is inhibited by the activities of immune deficiency (Imd), JAK/STAT, and Leu-rich repeat immune factors. We show that the exogenous siRNA pathway, thought of as the canonical mosquito antiviral pathway, plays no detectable role in antiviral defense in the midgut but only protects later in the systemic compartment. These results alter the prevailing antiviral paradigm by describing distinct protective mechanisms in different body compartments and infection stages. Importantly, the presence of the midgut bacterial flora is required for full viral infectivity to Anopheles, in contrast to malaria infection, where the presence of the midgut bacterial flora is required for protection against infection. Thus, the enteric flora controls a reciprocal protection tradeoff in the vector for resistance to different human pathogens.

  20. Intracoronary brachytherapy in the treatment of in-stent restenosis. Initial experience in Brazil

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    Fábio Sândoli de Brito Jr

    2001-09-01

    Full Text Available Intracoronary brachytherapy using beta or gamma radiation is currently the most efficient type of therapy for preventing the recurrence of coronary in-stent restenosis. Its implementation depends on the interaction among interventionists, radiotherapists, and physicists to assure the safety and quality of the method. The authors report the pioneering experience in Brazil of the treatment of 2 patients with coronary in-stent restenosis, in whom beta radiation was used as part of the international multicenter randomized PREVENT study (Proliferation REduction with Vascular ENergy Trial. The procedures were performed rapidly and did not require significant modifications in the traditional techniques used for conventional angioplasty. Alteration in the radiological protection devices of the hemodynamic laboratory were also not required, showing that intracoronary brachytherapy using beta radiation can be incorporated into the interventional tools of cardiology in our environment.

  1. Percutaneous endovascular stent-graft treatment of aortic aneurysms and dissections: new techniques and initial experience

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Do Yun; Choi, Dong Hoon; Kang, Sung Gwon; Lee, Kwang Hoon; Won, Jong Yun [Yonsei University College of Medicine, Seoul (Korea, Republic of); Kang, Sung Gwon [Chosun University College of Medicine, Gwangju (Korea, Republic of); Won, Je Whan [Aju University College of Medicine, Suwon (Korea, Republic of); Song, Ho Young [Ulsan University College of Medicine, Seoul (Korea, Republic of)

    2003-01-01

    To evaluate the feasibility, safety and effectiveness of a newly designed percutaneously implanted separate stent-graft (SSG) for the treatment of aortic aneurysms and dissections. Using a percutaneous technique, SSG placement (in the descending thoracic aorta in 26 cases and infrarenal abdominal aorta in 24) was attempted in 50 patients with aortic aneurysms (n=27) or dissection (n=23). All SSGs were individually constructed using self-expandable nitinol stents and a Dacron graft, and were introduced through a 12 F sheath and expanded to a diameter of 20-34 mm. In all cases, vascular access was through the femoral artery. The clinical status of each patient was monitored, and postoperative CT was performed within one week of the procedure and at 3-6 month intervals afterwards. Endovascular stent-graft deployment was technically successful in 49 of 50 patients (98%). The one failure was due to torsion of the unsupported graft during deployment. Successful exclusion of aneurysms and the primary entry tears of dissections was achieved in all but three patients with aortic dissection. All patients in whom technical success was achieved showed complete thrombosis of the thoracic false lumen or aneurysmal sac, and the overall technique success rate was 92%. In addition, sixteen patients demonstrated complete resolution of the dissected thoracic false lumen (n=9) or aneurysmal sac (n=7). Immediate post-operative complications occurred at the femoral puncture site in one patient with an arteriovenous fistula, and in two, a new saccular aneurysm developed at the distal margin of the stent. No patients died, and there was no instance of paraplegia, stroke, side-branch occlusion or infection during the subsequent mean follow-up period of 9.4 (range, 2 to 26) months. In patients with aortic aneurysm and dissection, treatment with a separate percutaneously inserted stent-graft is technically feasible, safe, and effective.

  2. Initial experience with extreme angle cervical screw for treatment of trauma and cervical spondylosis.

    Science.gov (United States)

    Mehta, Ankit I; Babu, Ranjith; Bagley, Carlos A; Grossi, Peter M; Gottfried, Oren N

    2014-03-01

    In this study, we have described our initial experience and surgical technique of extreme angle screw placement in the cervical and upper thoracic spine of a cohort of patients undergoing posterior fusion. This extreme angle screw facilitates rod placement without need for any coronal contouring of the rod or offset connectors despite the varied entry site locations for posterior instrumentation and the different trajectories and pathways of these screws. From ruary 2011 to July 2011, extreme angle screws were placed in twenty consecutive adult patients who underwent posterior cervical, occipital-cervical or cervical-thoracic fusions. The primary diagnosis was cervical spondylotic myelopathy (13), trauma (4), and pseudoarthrosis with stenosis (3). Eight patients had gross instability. A total of 196 screws were placed; half of the cases involved instrumentation at or within the C3-7 segments (10) and the others included constructs extending to occipital bone, C2, T1, or T2 (10). Of all twenty cases, there were no perioperative hardware complications. At long-term follow-up, two patients required reoperation, one for hardware failure and the other for single level symptomatic pseudoarthrosis. We conclude that extreme angle screw use in the posterior cervical spine provides an evolution in posterior instrumentation that maximizes the biomechanical strength of a construct, allows for easy rod placement, and may improve the restoration of sagittal alignment. Overall, extreme angle screws facilitate rod placement even for screws offset from the natural plane of the rod, thereby avoiding the need for coronal contouring or placement of offset connectors.

  3. CHALLENGES AND OPPORTUNITIES--INTEGRATED LIFE-CYCLE OPTIMIZATION INITIATIVES FOR THE HANFORD RIVER PROTECTION PROJECT--WASTE TREATMENT PLANT

    Energy Technology Data Exchange (ETDEWEB)

    Auclair, K. D.

    2002-02-25

    of issues across contract boundaries is a more difficult matter. This aspect, one of a seamless systems approach to the treatment of tank wastes at the Hanford site, is the focus of the Optimization Studies. This ''big O''Optimization of Life-Cycle operations is what is meant when the term ''optimization'' is used on the River Protection Project and initiatives cited in this paper. From the early contractor centric methods and processes used to move toward an integrated solution, through extensive partnering approaches, to the current quality initiatives with multi-organizational participation, significant progress is being made towards achieving the goal of truly integrated life-cycle optimization for the Department of Energy's River Protection Project and Waste Treatment Plant.

  4. Adherence to insulin treatment in insulin-naïve type 2 diabetic patients initiated on different insulin regimens

    Directory of Open Access Journals (Sweden)

    Gogas Yavuz D

    2015-08-01

    Full Text Available Dilek Gogas Yavuz, Sevim Ozcan, Oguzhan DeyneliDepartment of Endocrinology and Metabolism, Marmara University School of Medicine, Istanbul, TurkeyObjective: We aimed to evaluate adherence to insulin treatment in terms of treatment persistence and daily adherence to insulin injections among insulin-naïve type 2 diabetic patients initiating insulin therapy with basal (long acting, basal-bolus, and premixed insulin regimens in a tertiary endocrinology outpatient clinic.Methods: A total of 433 (mean age of 55.5±13.0 years; 52.4% females insulin-naïve type 2 diabetic patients initiated on insulin therapy were included in this questionnaire-based phone interview survey at the sixth month of therapy. Via the telephone interview questions, patients were required to provide information about persistence to insulin treatment, self-reported blood glucose values, and side effects; data on demographics and diabetes characteristics were obtained from medical records.Results: Self-reported treatment withdrawal occurred in 20.1% patients, while 20.3% patients were nonadherent to daily insulin. Negative beliefs about insulin therapy (24.1% and forgetting injections (40.9% were the most common reasons for treatment withdrawal and dose skipping, respectively. Younger age (49.5±15.0 vs 56.4±12.0 years (P=0.001 and shorter duration of diabetes (4.8±4.3 vs 8.8±6.3 years (P=0.0008 and treatment duration (5.2±2.4 vs 10.7±2.4 months (P=0.0001 were noted, respectively, in discontinuers vs continuers. Basal bolus was the most commonly prescribed insulin regimen (51.0%, while associated with higher likelihood of skipping a dose than regular use (61.3% vs. 46.0%, P=0.04.Conclusions: Persistence to insulin therapy was poorer than anticipated but appeared to be higher in patients with the basal bolus regimen. Negative perceptions about insulin therapy seemed to be the main cause for poor adherence in our cohort.Keywords: type 2 diabetes, insulin treatment adherence

  5. Curious discoveries in antiviral drug development: the role of serendipity.

    Science.gov (United States)

    De Clercq, Erik

    2015-07-01

    Antiviral drug development has often followed a curious meandrous route, guided by serendipity rather than rationality. This will be illustrated by ten examples. The polyanionic compounds (i) polyethylene alanine (PEA) and (ii) suramin were designed as an antiviral agent (PEA) or known as an antitrypanosomal agent (suramin), before they emerged as, respectively, a depilatory agent, or reverse transcriptase inhibitor. The 2',3'-dideoxynucleosides (ddNs analogues) (iii) have been (and are still) used in the "Sanger" DNA sequencing technique, although they are now commercialized as nucleoside reverse transcriptase inhibitors (NRTIs) in the treatment of HIV infections. (E)-5-(2-Bromovinyl)-2'-deoxyuridine (iv) was discovered as a selective anti-herpes simplex virus compound and is now primarily used for the treatment of varicella-zoster virus infections. The prototype of the acyclic nucleoside phosphonates (ANPs), (S)-9-(3-hydroxy-2-phosphonylmethoxypropyl)adenine [(S)-HPMPA], (v) was never commercialized, although it gave rise to several marketed products (cidofovir, adefovir, and tenofovir). 1-[2-(Hydroxyethoxy)methyl]-6-(phenylthio)thymine (vi) and TIBO (tetrahydroimidazo[4,5,1-jk][1,4-benzodiazepin-2(1H)]-one and -thione) (vii) paved the way to a number of compounds (i.e., nevirapine, delavirdine, etravirine, and rilpivirine), which are now collectively called non-NRTIs. The bicyclam AMD3100 (viii) was originally described as an anti-HIV agent before it became later marketed as a stem cell mobilizer. The S-adenosylhomocysteine hydrolase inhibitors (ix), while active against a broad range of (-)RNA viruses and poxviruses may be particularly effective against Ebola virus, and for (x) the O-ANP derivatives, the potential application range encompasses virtually all DNA viruses.

  6. Initial assessment and treatment with the Airway, Breathing, Circulation, Disability, Exposure (ABCDE approach

    Directory of Open Access Journals (Sweden)

    Thim T

    2012-01-01

    Full Text Available Troels Thim1,2, Niels Henrik Vinther Krarup1,4, Erik Lerkevang Grove1, Claus Valter Rohde3, Bo Løfgren1,41Department of Cardiology, Aarhus University Hospital, Aarhus, 2Department of Internal Medicine, Regional Hospital of Randers, Randers, 3Department of Anestesiology, Aarhus University Hospital, Aarhus, 4Research Center for Emergency Medicine, Aarhus University Hospital, Aarhus, DenmarkAbstract: The Airway, Breathing, Circulation, Disability, Exposure (ABCDE approach is applicable in all clinical emergencies for immediate assessment and treatment. The approach is widely accepted by experts in emergency medicine and likely improves outcomes by helping health care professionals focusing on the most life-threatening clinical problems. In an acute setting, high-quality ABCDE skills among all treating team members can save valuable time and improve team performance. Dissemination of knowledge and skills related to the ABCDE approach are therefore needed. This paper offers a practical “how-to” description of the ABCDE approach.Keywords: emergency medicine, general medicine, internal medicine, multiple trauma, multiple injury

  7. Toxoplasmosis Titers and past Suicide Attempts Among Older Adolescents Initiating SSRI Treatment.

    Science.gov (United States)

    Coryell, William; Yolken, Robert; Butcher, Brandon; Burns, Trudy; Dindo, Lilian; Schlechte, Janet; Calarge, Chadi

    2016-01-01

    Latent infection with toxoplasmosis is a prevalent condition that has been linked in animal studies to high-risk behaviors, and in humans, to suicide and suicide attempts. This analysis investigated a relationship between suicide attempt history and toxoplasmosis titers in a group of older adolescents who had recently begun treatment with an SSRI. Of 108 participants, 17 (15.7 %) had a lifetime history of at least one suicide attempt. All were given structured and unstructured diagnostic interviews and provided blood samples. Two individuals (11.9%) with a past suicide attempt, and two (2.1%) without this history, had toxoplasmosis titers ≥ 10 IU/ml (p = 0.166). Those with a past suicide attempt had mean toxoplasmosis titers that were significantly different (p = 0.018) from those of patients who lacked this history. An ROC analysis suggested a lower optimal threshold for distinguishing patients with and without suicide attempts (3.6 IU/ml) than that customarily used to identify seropositivity. Toxoplasmosis titers may quantify a proneness to suicidal behavior in younger individuals being treated with antidepressants.

  8. Genetic diversity of the hepatitis C virus: Impact and issues in the antiviral therapy

    Institute of Scientific and Technical Information of China (English)

    H Le Guillou-Guillemette; S Vallet; C Gaudy-Graffin; C Payan; A Pivert; A Goudeau; F Lunel-Fabiani

    2007-01-01

    The hepatitis C Virus (HCV) presents a high degree of genetic variability which is explained by the combination of a lack of proof reading by the RNA dependant RNA polymerase and a high level of viral replication. The resuiting genetic polymorphism defines a classification in clades, genotypes, subtypes, isolates and quasispecies.This diversity is known to reflect the range of responses to Interferon therapy. The genotype is one of the predictive parameters currently used to define the antiviral treatment strategy and the chance of therapeutic success. Studies have also reported the potential impact of the viral genetic polymorphism in the outcome of antiviral therapy in patients infected by the same HCV genotype. Both structural and non structural genomic regions of HCV have been suggested to be involved in the Interferon pathway and the resistance to antiviral therapy. In this review, we first detail the viral basis of HCV diversity.Then, the HCV genetic regions that may be implicated in resistance to therapy are described, with a focus on the structural region encoded by the E2 gene and the non-structural genes NS3, NS5A and NS5B. Both mechanisms of the Interferon resistance and of the new antiviral drugs are described in this review.

  9. Use of Antiviral Prophylaxis in Influenza Outbreaks in Long Term Care Facilities

    Directory of Open Access Journals (Sweden)

    Allison McGeer

    2000-01-01

    Full Text Available Influenza is a major cause of illness and death in residents of long term care facilities for the elderly, in part because residents' age and underlying illness increase the risk of serious complications, and in part because institutional living increases the risk of influenza outbreaks. The administration of antiviral medications active against influenza to persons exposed to influenza has been shown to protect them effectively from illness, and mass antiviral prophylaxis of residents is an effective means of terminating influenza A outbreaks in long term care facilities. The only antiviral currently licensed in Canada for influenza prophylaxis is amantadine, a medication active against influenza A but not influenza B. The National Advisory Committee on Immunization recommends that amantadine prophylaxis be offered to residents when influenza A outbreaks occur in long term care facilities. However, there remain a number of unanswered questions about how best to use amantadine for controlling influenza A outbreaks in long term care facilities. In addition, two members of a new class of antivirals called neuraminidase inhibitors have recently been licensed in Canada for the treatment of influenza, and are effective in prophylaxis. Issues in the use of amantadine in the control of outbreaks of influenza A in long term care facilities for the elderly are reviewed, and the potential uses of neuraminidase inhibitors in this setting are discussed.

  10. Neopterin as a Marker of Response to Antiviral Therapy in Hepatitis C Virus Patients

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    Gregory F. Oxenkrug

    2012-01-01

    Full Text Available Predicting the efficacy of antiviral treatment of hepatitis C virus (HCV is of importance for both patient well-being and health care expense. The expression of interferon-stimulated genes (IFN-SGs in the liver was suggested as a marker of response to anti-viral therapy. IFN-SGs encode the guanosine triphosphate cyclohydrolase 1 (GTPCH, a rate-limiting enzyme of pteridines biosynthesis. Neopterin, a stable byproduct of GTPCH-catalyzed reaction, is used as a marker of interferon-induced GTPCH activation. We hypothesized that assessment of neopterin concentrations might predict the response to antiviral therapy. Neopterin concentrations were evaluated in 260 HCV patients treated by pegylated interferon combined with ribavirin. Mean and median pretreatment neopterin concentrations were lower in patients with sustained virological response than in nonresponders. The rate of response was twofold higher among patients with pretreatment neopterin levels <16 nmol/L than in patients with neopterin levels ≥16 nmol/L, even after controlling for HCV genotype status. Our study suggests that the pretreatment level of neopterin might be used in routine clinical practice as rapid and cost-effective marker to predict the response to antiviral therapy in HCV patients.

  11. Evasion of the Interferon-Mediated Antiviral Response by Filoviruses

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    Washington B. Cárdenas

    2010-01-01

    Full Text Available The members of the filoviruses are recognized as some of the most lethal viruses affecting human and non-human primates. The only two genera of the Filoviridae family, Marburg virus (MARV and Ebola virus (EBOV, comprise the main etiologic agents of severe hemorrhagic fever outbreaks in central Africa, with case fatality rates ranging from 25 to 90%. Fatal outcomes have been associated with a late and dysregulated immune response to infection, very likely due to the virus targeting key host immune cells, such as macrophages and dendritic cells (DCs that are necessary to mediate effective innate and adaptive immune responses. Despite major progress in the development of vaccine candidates for filovirus infections, a licensed vaccine or therapy for human use is still not available. During the last ten years, important progress has been made in understanding the molecular mechanisms of filovirus pathogenesis. Several lines of evidence implicate the impairment of the host interferon (IFN antiviral innate immune response by MARV or EBOV as an important determinant of virulence. In vitro and in vivo experimental infections with recombinant Zaire Ebola virus (ZEBOV, the best characterized filovirus, demonstrated that the viral protein VP35 plays a key role in inhibiting the production of IFN-α/β. Further, the action of VP35 is synergized by the inhibition of cellular responses to IFN-α/β by the minor matrix viral protein VP24. The dual action of these viral proteins may contribute to an efficient initial virus replication and dissemination in the host. Noticeably, the analogous function of these viral proteins in MARV has not been reported. Because the IFN response is a major component of the innate immune response to virus infection, this chapter reviews recent findings on the molecular mechanisms of IFN-mediated antiviral evasion by filovirus infection.

  12. Dialysate White Blood Cell Change after Initial Antibiotic Treatment Represented the Patterns of Response in Peritoneal Dialysis-Related Peritonitis

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    Pichaya Tantiyavarong

    2016-01-01

    Full Text Available Background. Patients with peritoneal dialysis-related peritonitis usually have different responses to initial antibiotic treatment. This study aimed to explore the patterns of response by using the changes of dialysate white blood cell count on the first five days of the initial antibiotic treatment. Materials and Methods. A retrospective cohort study was conducted. All peritoneal dialysis-related peritonitis episodes from January 2014 to December 2015 were reviewed. We categorized the patterns of antibiotic response into 3 groups: early response, delayed response, and failure group. The changes of dialysate white blood cell count for each pattern were determined by multilevel regression analysis. Results. There were 644 episodes in 455 patients: 378 (58.7% of early response, 122 (18.9% of delayed response, and 144 (22.3% of failure episodes. The patterns of early, delayed, and failure groups were represented by the average rate reduction per day of dialysate WBC of 68.4%, 34.0%, and 14.2%, respectively (p value < 0.001 for all comparisons. Conclusion. Three patterns, which were categorized by types of responses, have variable rates of WBC declining. Clinicians should focus on the delayed response and failure patterns in order to make a decision whether to continue medical therapies or to aggressively remove the peritoneal catheter.

  13. [Amoxicillin and clavulanic acid versus amoxicillin plus gentamicin in the empirical initial treatment of urinary tract infections in hospitalized patients].

    Science.gov (United States)

    Verzasconi, R; Rodoni, P; Monotti, R; Marone, C; Mombelli, G

    1995-08-19

    We compared the fixed combination amoxicillin plus clavulanic acid with that of amoxicillin plus gentamicin in the empirical initial treatment of severe urinary tract infections. The study included 87 hospitalized patients (51 women and 36 men, mean age 58 +/- 22 years) with acute uncomplicated pyelonephritis (n = 48) or with complicated urinary tract infections (n = 39). 80 patients (92%) had fever and 31 patients (36%) positive blood cultures. 45 patients were randomly assigned to amoxicillin plus clavulanic acid and 42 to amoxicillin plus gentamicin. Overall, 18 patients (21%) were infected with organisms resistant in vitro to amoxicillin plus clavulanic acid, whereas no pathogen was isolated with resistance to amoxicillin plus gentamicin (p amoxicillin plus gentamicin (p amoxicillin plus gentamicin group. Although the in-vitro resistance did not result in a lower clinical efficacy of amoxicillin plus clavulanic acid compared to amoxicillin plus gentamicin in our relatively small sample of patients, the data indicate that the antimicrobial activity of amoxicillin plus clavulanic acid is inadequate to cover the spectrum of causative agents in hospitalized patients with pyelonephritis or complicated urinary tract infections. Amoxicillin plus clavulanic acid should therefore not be used in the initial empirical treatment of these infections.

  14. Prescribing patterns, adherence and LDL-cholesterol response of type 2 diabetes patients initiating statin on low-dose versus standard-dose treatment : a descriptive study

    NARCIS (Netherlands)

    de Vries, F M; Voorham, J; Hak, E; Denig, P

    2016-01-01

    AIMS: The aim of this study was to describe and compare treatment modifications and discontinuation, adherence levels and response to treatment in patients with type 2 diabetes initiating on low-dose vs. standard-dose statin treatment. METHODS: A 2-year follow-up cohort study was performed using dat

  15. A modified MS2 bacteriophage plaque reduction assay for the rapid screening of antiviral plant extracts

    Directory of Open Access Journals (Sweden)

    Ian Cock

    2010-01-01

    Full Text Available Introduction: Traditional methods of screening plant extracts and purified components for antiviral activity require up to a week to perform, prompting the need to develop more rapid quantitative methods to measure the ability of plant based preparations to block viral replication. We describe an adaption of an MS2 plaque reduction assay for use in S. aureus. Results: MS2 bacteriophage was capable of infecting and replicating in B. cereus, S. aureus and F+ E. coli but not F- E. coli. Indeed, both B. cereus and S. aureus were more sensitive to MS2 induced lysis than F+ E. coli. When MS2 bacteriophage was mixed with Camellia sinensis extract (1 mg/ml, Scaevola spinescens extract (1 mg/ml or Aloe barbadensis juice and the mixtures inoculated into S. aureus, the formation of plaques was reduced to 8.9 ± 3.8%, 5.4 ± 2.4% and 72.7 ± 20.9% of the untreated MS2 control values respectively. Conclusions: The ability of the MS2 plaque reduction assay to detect antiviral activity in these known antiviral plant preparations indicates its suitability as an antiviral screening tool. An advantage of this assay compared with traditionally used cytopathic effect reduction assays and replicon based assays is the more rapid acquisition of results. Antiviral activity was detected within 24 h of the start of testing. The MS2 assay is also inexpensive and non-pathogenic to humans making it ideal for initial screening studies or as a simulant for pathogenic viruses.

  16. [Hepatitis C: diagnosis, anti-viral therapy, after-care. Hungarian consensus guideline].

    Science.gov (United States)

    Hunyady, Béla; Gerlei, Zsuzsanna; Gervain, Judit; Horváth, Gábor; Lengyel, Gabriella; Pár, Alajos; Rókusz, László; Szalay, Ferenc; Telegdy, László; Tornai, István; Werling, Klára; Makara, Mihály

    2015-03-01

    Approximately 70,000 people are infected with hepatitis C virus in Hungary, and more than half of them are not aware of their infection. From the point of infected individuals early recognition and effective treatment of related liver injury may prevent consequent advanced liver diseases and complications (liver cirrhosis, liver failure and liver cancer) and can increase work productivity and life expectancy. Furthermore, these could from prevent further spread of the virus as well as reduce substantially long term financial burden of related morbidity, as a socioeconomic aspect. Pegylated interferon + ribavirin dual therapy, which is available in Hungary since 2003, can clear the virus in 40-45% of previously not treated (naïve), and in 5-21% of previous treatment-failure patients. Addition of a direct acting first generation protease inhibitor drug (boceprevir or telaprevir) to the dual therapy increases the chance of sustained viral response to 63-75% and 59-66%, respectively. These two protease inhibitors are available and financed for a segment of Hungarian patients since May 2013. Between 2013 and February 2015, other direct acting antivirals and interferon-free combination therapies have been registered for the treatment of chronic hepatitis C with a potential efficacy over 90% and typically with a short duration of 8-12 weeks. Indication of therapy includes exclusion of contraindications to the drugs and demonstration of viral replication with consequent liver injury, i.e., inflammation and/or fibrosis in the liver. Non-invasive methods (elastography and biochemical methods) are accepted and preferred for staging liver damage (fibrosis). For initiation of treatment accurate and timely molecular biology tests are mandatory. Eligibility for treatment is a subject of individual central medical review. Due to budget limitations therapy is covered only for a proportion of patients by the National Health Insurance Fund. Priority is given to those with urgent

  17. Histophilus somni Stimulates Expression of Antiviral Proteins and Inhibits BRSV Replication in Bovine Respiratory Epithelial Cells.

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    C Lin

    Full Text Available Our previous studies showed that bovine respiratory syncytial virus (BRSV followed by Histophilus somni causes more severe bovine respiratory disease and a more permeable alveolar barrier in vitro than either agent alone. However, microarray analysis revealed the treatment of bovine alveolar type 2 (BAT2 epithelial cells with H. somni concentrated culture supernatant (CCS stimulated up-regulation of four antiviral protein genes as compared with BRSV infection or dual treatment. This suggested that inhibition of viral infection, rather than synergy, may occur if the bacterial infection occurred before the viral infection. Viperin (or radical S-adenosyl methionine domain containing 2--RSAD2 and ISG15 (IFN-stimulated gene 15--ubiquitin-like modifier were most up-regulated. CCS dose and time course for up-regulation of viperin protein levels were determined in treated bovine turbinate (BT upper respiratory cells and BAT2 lower respiratory cells by Western blotting. Treatment of BAT2 cells with H. somni culture supernatant before BRSV infection dramatically reduced viral replication as determined by qRT PCR, supporting the hypothesis that the bacterial infection may inhibit viral infection. Studies of the role of the two known H. somni cytotoxins showed that viperin protein expression was induced by endotoxin (lipooligosaccharide but not by IbpA, which mediates alveolar permeability and H. somni invasion. A naturally occurring IbpA negative asymptomatic carrier strain of H. somni (129Pt does not cause BAT2 cell retraction or permeability of alveolar cell monolayers, so lacks virulence in vitro. To investigate initial steps of pathogenesis, we showed that strain 129Pt attached to BT cells and induced a strong viperin response in vitro. Thus colonization of the bovine upper respiratory tract with an asymptomatic carrier strain lacking virulence may decrease viral infection and the subsequent enhancement of bacterial respiratory infection in vivo.

  18. Early versus delayed initiation of antiretroviral therapy for Indian HIV-Infected individuals with tuberculosis on antituberculosis treatment

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    Sinha Sanjeev

    2012-07-01

    Full Text Available Abstract Background For antiretroviral therapy (ART naive human immunodeficiency virus (HIV infected adults suffering from tuberculosis (TB, there is uncertainty about the optimal time to initiate highly active antiretroviral therapy (HAART after starting antituberculosis treatment (ATT, in order to minimize mortality, HIV disease progression, and adverse events. Methods In a randomized, open label trial at All India Institute of Medical Sciences, New Delhi, India, eligible HIV positive individuals with a diagnosis of TB were randomly assigned to receive HAART after 2-4 or 8-12 weeks of starting ATT, and were followed for 12 months after HAART initiation. Participants received directly observed therapy short course (DOTS for TB, and an antiretroviral regimen comprising stavudine or zidovudine, lamivudine, and efavirenz. Primary end points were death from any cause, and progression of HIV disease marked by failure of ART. Findings A total of 150 patients with HIV and TB were initiated on HAART: 88 received it after 2-4 weeks (early ART and 62 after 8-12 weeks (delayed ART of starting ATT. There was no significant difference in mortality between the groups after the introduction of HAART. However, incidence of ART failure was 31% in delayed versus 16% in early ART arm (p = 0.045. Kaplan Meier disease progression free survival at 12 months was 79% for early versus 64% for the delayed ART arm (p = 0.05. Rates of adverse events were similar. Interpretation Early initiation of HAART for patients with HIV and TB significantly decreases incidence of HIV disease progression and has good tolerability. Trial registration CTRI/2011/12/002260

  19. Research progress in the development of direct acting antiviral agents for hepatitis C and the anti-viral resistance

    Directory of Open Access Journals (Sweden)

    Song YANG

    2011-05-01

    Full Text Available Recently,directly acting antiviral agents against hepatitic C virus with different mechanisms have been developed and put into clinical trials.Especially,results of phase Ⅲ clinical trials of Boceprevir and Telaprevir have been published,and these two agents are to be approved for marketing in recent years.Also much attention has been paid on anti-viral resistance against direct acting antiviral agents.Great progresses have been made in field of direct acting antiviral agents against hepatitic C virus.Domestic studies in this area should take characteristics of virus and host of Chinese chronic hepatitis C into consideration.

  20. SU-E-T-502: Initial Results of a Comparison of Treatment Plans Produced From Automated Prioritized Planning Method and a Commercial Treatment Planning System

    Energy Technology Data Exchange (ETDEWEB)

    Tiwari, P; Chen, Y [Memorial Sloan Kettering Cancer Center, New York, NY (United States); Hong, L; Apte, A; Yang, J; Mechalakos, J; Mageras, G; Hunt, M; Deasy, J [Washington University in St. Louis (United States)

    2015-06-15

    Purpose We developed an automated treatment planning system based on a hierarchical goal programming approach. To demonstrate the feasibility of our method, we report the comparison of prostate treatment plans produced from the automated treatment planning system with those produced by a commercial treatment planning system. Methods In our approach, we prioritized the goals of the optimization, and solved one goal at a time. The purpose of prioritization is to ensure that higher priority dose-volume planning goals are not sacrificed to improve lower priority goals. The algorithm has four steps. The first step optimizes dose to the target structures, while sparing key sensitive organs from radiation. In the second step, the algorithm finds the best beamlet weight to reduce toxicity risks to normal tissue while holding the objective function achieved in the first step as a constraint, with a small amount of allowed slip. Likewise, the third and fourth steps introduce lower priority normal tissue goals and beam smoothing. We compared with prostate treatment plans from Memorial Sloan Kettering Cancer Center developed using Eclipse, with a prescription dose of 72 Gy. A combination of liear, quadratic, and gEUD objective functions were used with a modified open source solver code (IPOPT). Results Initial plan results on 3 different cases show that the automated planning system is capable of competing or improving on expert-driven eclipse plans. Compared to the Eclipse planning system, the automated system produced up to 26% less mean dose to rectum and 24% less mean dose to bladder while having the same D95 (after matching) to the target. Conclusion We have demonstrated that Pareto optimal treatment plans can be generated automatically without a trial-and-error process. The solver finds an optimal plan for the given patient, as opposed to database-driven approaches that set parameters based on geometry and population modeling.

  1. 直接抗病毒药物治疗丙型肝炎肝硬化早期抗病毒疗效及安全性临床实践研究%Early efficacy and safety of direct-acting antiviral agents for the treatment of cirrhotic patients with hepatitis C

    Institute of Scientific and Technical Information of China (English)

    安子英; 盛秋菊; 张翀; 白菡; 王静艳; 窦晓光; 丁洋

    2016-01-01

    Objective To evaluate early efficacy and safety of direct-acting antiviral agents (DAAs) for the treatment of cirrhotic patients with hepatitis C.Methods HCV genotype 1b patients with cirrhosis were treated with DAAs [treatment protocol 1: sofosbuvir+ribavirin (RBV), treatment protocol 2: sofosbuvir+ledipasvir+RBV, treatment protocol 3: sofosbuvir+daclatasvir+RBV] for 24 weeks. Virological and biochemical markers were monitored at different time points, and adverse reactions were observed. This study focused on the analysis of the data obtained from 24 patients receiving 12 weeks of treatment.Results Of 24 patients, who had completed 12 weeks of treatment, 12 received treatment protocol 1, 6 treatment protocol 2, and the other 6 treatment protocol 3. Negative conversion rates of HCV RNA at week 1, 2, 4 and 12 were 25.00% (6/24), 45.83% (11/24), 66.67% (16/24) and 70.83% (17/24), respectively. Prolonged DAAs treatment resulted in an increased negative conversion rate of HCV RNA. Of patients receiving treatment protocol 1, HCV RNA negative conversion was obtained in 4 na?ve patients and 1 experienced patient at week 12 of treatment. Of patients receiving treatment protocol 2 and 3, HCV RNA negative conversion was obtained in 3 na?ve patients and 3 experienced patients at week 12 of treatment, respectively. As of January 2016, 3 patients were followed up for 12 weeks after medication cessation, of whom the 1 patient receiving treatment protocol 1 relapsed after medication cessation for 12 weeks with HCV RNA of 1.8×106 IU/ml, and the other 2 patients receiving treatment protocol 2 achieved sustained virological response with HCV RNA undetectable. ALT decreased to normal after 2 weeks of treatment and kept normal at week 12. Both CK and CK-MB elevated slightly after 1 week of treatment, but there were no significant differences at baseline and week 1. The two markers decreased to normal after 2 weeks of treatment and kept normal at week 12. BUN and CRE didn't increase

  2. Assessment of Antiviral Properties of Peramivir against H7N9 Avian Influenza Virus in an Experimental Mouse Model

    Science.gov (United States)

    Farooqui, Amber; Huang, Linxi; Wu, Suwu; Cai, Yingmu; Su, Min; Lin, Pengzhou; Chen, Weihong; Fang, Xibin; Zhang, Li; Liu, Yisu; Zeng, Tiansheng; Paquette, Stephane G.; Khan, Adnan; Kelvin, Alyson A.

    2015-01-01

    The H7N9 influenza virus causes a severe form of disease in humans. Neuraminidase inhibitors, including oral oseltamivir and injectable peramivir, are the first choices of antiviral treatment for such cases; however, the clinical efficacy of these drugs is questionable. Animal experimental models are essential for understanding the viral replication kinetics under the selective pressure of antiviral agents. This study demonstrates the antiviral activity of peramivir in a mouse model of H7N9 avian influenza virus infection. The data show that repeated administration of peramivir at 30 mg/kg of body weight successfully eradicated the virus from the respiratory tract and extrapulmonary tissues during the acute response, prevented clinical signs of the disease, including neuropathy, and eventually protected mice against lethal H7N9 influenza virus infection. Early treatment with peramivir was found to be associated with better disease outcomes. PMID:26369969

  3. Clinical observation of chronic hepatitis C patients with Hashimoto' s thyroiditis by antiviral treatment%慢性丙型肝炎合并桥本甲状腺炎12例抗病毒治疗疗效观察

    Institute of Scientific and Technical Information of China (English)

    滕志兰; 张树青

    2012-01-01

    Objective To investigate the effect of thyroid function of chronic hepatitis C patients with Hashimoto's thyroiditis and anti-viral treatment and securit.Methods Twelve chronic hepatitis C patients with Hashimoto' s thyroiditis,were treated with interferon-α.The thyroid function of patients was observed in the treatment and 24 weeks after the end of treatment.Results The incidence of thyroid dysfunction among chronic hepatitis C patients with Hashimoto' s thyroiditis was 91.7% (11/12),and 24 weeks after the end of treatment,the incidence of thyroid dysfunction among chronic hepatitis C patients with Hashimoto' s thyroiditis was 33.3% (4/12).The mainly symptom of thyroid dysfunction was hypothyroidism.The virological response were 66.67% (8/12),83.33% (10/12),100% (12/12) and 66.67% (8/12) after the 4 weeks,12 weeks,24 weeks treatment and 24 weeks after the end of treatment.Conclusions Chronic hepatitis C patients with Hashimoto' s thyroiditis treated with interferon-α individually are more prone to thyroid dysfunction,but clinical symptoms are not obvious.It can be completed under the monitoring,and can be satisfied with the antiviral efficacy.%目的 探讨干扰素-α对慢性丙型肝炎合并桥本甲状腺炎患者甲状腺功能的影响,及抗病毒治疗的方法及安全性.方法 对12例合并桥本甲状腺炎的慢性丙型肝炎患者,采取干扰素-α个体化给药,观察治疗过程中及治疗结束后24周患者甲状腺功能的变化.结果 12例患者在治疗中甲状腺功能异常发生率为91.7%(11/12),主要表现为甲状腺功能减退,治疗结束24周仍有33.3%(4/12)患者甲状腺功能异常.抗病毒治疗4、12、24周及治疗结束后24周累计病毒学应答率分别为66.67%(8/12)、83.33%(10/12)、100%(12/12)和66.67%(8/12).结论 干扰素-α个体化给药治疗慢性丙型肝炎合并桥本甲状腺炎,虽然较易发生甲状腺功能异常,但临床症状多不明显,在严密监测下可

  4. Autophagy is involved in anti-viral activity of pentagalloylglucose (PGG) against Herpes simplex virus type 1 infection in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Pei, Ying, E-mail: peiying-19802@163.com [Biomedicine Research and Development Center of Jinan University, Guangzhou, Guangdong 510632 (China); Chen, Zhen-Ping, E-mail: 530670663@qq.com [Biomedicine Research and Development Center of Jinan University, Guangzhou, Guangdong 510632 (China); Ju, Huai-Qiang, E-mail: 344464448@qq.com [Biomedicine Research and Development Center of Jinan University, Guangzhou, Guangdong 510632 (China); Komatsu, Masaaki, E-mail: komatsu-ms@igakuken.or.jp [Laboratory of Frontier Science, Tokyo Metropolitan Institute of Medical Science, Bunkyo-ku, Tokyo 113-8613 (Japan); Ji, Yu-hua, E-mail: tjyh@jnu.edu.cn [Institute of Tissue Transplantation and Immunology, College of Life Science and Technology, Jinan University, Guangzhou 510632 (China); Liu, Ge, E-mail: lggege_15@hotmail.com [Division of Molecular Pharmacology of Infectious agents, Department of Molecular Microbiology and Immunology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8521 (Japan); Guo, Chao-wan, E-mail: chaovan_kwok@hotmail.com [Division of Molecular Pharmacology of Infectious agents, Department of Molecular Microbiology and Immunology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8521 (Japan); Zhang, Ying-Jun, E-mail: zhangyj@mail.kib.ac.cn [Kunming Institute of Botany, the Chinese Academy of Sciences, Yunnan, Kunming 650204 (China); Yang, Chong-Ren, E-mail: cryang@mail.kib.ac.cn [Kunming Institute of Botany, the Chinese Academy of Sciences, Yunnan, Kunming 650204 (China); Wang, Yi-Fei, E-mail: twang-yf@163.com [Biomedicine Research and Development Center of Jinan University, Guangzhou, Guangdong 510632 (China); Kitazato, Kaio, E-mail: kkholi@msn.com [Division of Molecular Pharmacology of Infectious agents, Department of Molecular Microbiology and Immunology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8521 (Japan)

    2011-02-11

    Research highlights: {yields} We showed PGG has anti-viral activity against Herpes simplex virus type 1 (HSV-1) and can induce autophgy. {yields} Autophagy may be a novel and important mechanism mediating PGG anti-viral activities. {yields} Inhibition of mTOR pathway is an important mechanism of induction of autophagy by PGG. -- Abstract: Pentagalloylglucose (PGG) is a natural polyphenolic compound with broad-spectrum anti-viral activity, however, the mechanisms underlying anti-viral activity remain undefined. In this study, we investigated the effects of PGG on anti-viral activity against Herpes simplex virus type 1 (HSV-1) associated with autophagy. We found that the PGG anti-HSV-1 activity was impaired significantly in MEF-atg7{sup -/-} cells (autophagy-defective cells) derived from an atg7{sup -/-} knockout mouse. Transmission electron microscopy revealed that PGG-induced autophagosomes engulfed HSV-1 virions. The mTOR signaling pathway, an essential pathway for the regulation of autophagy, was found to be suppressed following PGG treatment. Data presented in this report demonstrated for the first time that autophagy induced following PGG treatment contributed to its anti-HSV activity in vitro.

  5. 抗病毒治疗对慢性乙型肝炎患者免疫球蛋白及补体的影响%The impact of serum levels of immunoglobulin and complement during nucleoside antiviral treatment in chronic hepatitis B patients

    Institute of Scientific and Technical Information of China (English)

    谢婵; 谢俊强; 张宇锋; 谢冬英; 谢仕斌; 彭亮; 林炳亮; 高志良

    2012-01-01

    目的 探讨慢性乙型肝炎(慢乙肝)患者使用核苷类抗病毒药物前后对免疫球蛋白及补体的影响.方法 选取慢乙肝患者共157例,50例接受抗病毒治疗,分别在其使用核苷类抗病毒药物前,抗病毒治疗后的第1、2、3、4周,用ELISA法检测HBV血清学标志物,RT-PCR法检测HBV DNA,免疫比浊法测定IgG、IgA、IgM和C3、C4、总补体(CH50)、C反应蛋白(CRP).均数比较采用t检验和Mann-Whitney检验.相关分析采用Pearson相关系数检验.结果 慢性乙型重型肝炎及肝硬化组患者的IgA、IgM明显高于慢乙肝组(P<0.01).三组间C3、C4、CH50、CRP水平比较,差异有统计学意义.HBeAg阳性与HBeAg阴性患者的C3、IgM、IgG及HBV DNA水平比较,差异有统计学意义.HBeAg阳性者中,高HBV DNA水平的患者与低水平HBV DNA患者相比,其IgA、IgM、C3和CH50水平均差异有统计学意义.HBeAg阴性患者中,高HBV DNA水平的患者与低水平HBV DNA患者相比,IgA水平差异有统计学意义.经抗病毒治疗,三组患者的免疫球蛋白及HBV DNA较治疗前下降,补体系统较前回升,在第4周时差异有统计学意义.HBV DNA的水平与C3呈负相关(r=-0.78,P=0.021).HBeAg定量与C3呈正相关(r=0.87,P=0.015).结论 血清免疫球蛋白、CRP、C3、C4和CH50可以反映肝脏炎性活动状态;C3的变化可以预测抗病毒治疗的效果.%Objective To evaluate the effects of nucleoside/nucleotide analogue treatment on immunoglobulin and complement in patients with chronic hepatitis B (CHB).Methods A total of 157 CHB patients were recruited and divided into CHB group,liver cirrhosis (LC) group and severe hepatitis B (SHB) group.There were 50 patients who received oral antiviral treatment (lamivudine 100 mg/d,or entecavir 0.5 mg/d,or telbivudine 600 mg/d).Serum levels of complement 3 and 4 (C3,C4),C-reaction protein (CRP),hemolytic complement (CH50),immunoglobulin G,M,A (IgG,IgM,IgA),hepatitis B surface antigen (HBsAg) and hepatitis

  6. Effect of antiviral prophylaxis on influenza outbreaks om aged care facilities in three local health districts in New South Wales, Australia, 2014

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    Tony Merritt

    2016-02-01

    Full Text Available Background: There was a record number (n = 111 of influenza outbreaks in aged care facilities in New South Wales, Australia during 2014. To determine the impact of antiviral prophylaxis recommendations in practice, influenza outbreak data were compared for facilities in which antiviral prophylaxis and treatment were recommended and for those in which antivirals were recommended for treatment only. Methods: Routinely collected outbreak data were extracted from the Notifiable Conditions Information Management System for two Local Health Districts where antiviral prophylaxis was routinely recommended and one Local Health District where antivirals were recommended for treatment but not routinely for prophylaxis. Data collected on residents included counts of influenza-like illness, confirmed influenza, hospitalizations and related deaths. Dates of onset, notification, influenza confirmation and antiviral recommendations were also collected for analysis. The Mann–Whitney U test was used to assess the significance of differences between group medians for key parameters. Results: A total of 41 outbreaks (12 in the prophylaxis group and 29 in the treatment-only group were included in the analysis. There was no significant difference in overall outbreak duration; outbreak duration after notification; or attack, hospitalization or case fatality rates between the two groups. The prophylaxis group had significantly higher cases with influenza-like illness (P = 0.03 and cases recommended antiviral treatment per facility (P = 0.01. Discussion: This study found no significant difference in key outbreak parameters between the two groups. However, further high quality evidence is needed to guide the use of antivirals in responding to influenza outbreaks in aged care facilities.

  7. Antiviral Defenses in Plants through Genome Editing

    Science.gov (United States)

    Romay, Gustavo; Bragard, Claude

    2017-01-01

    Plant–virus interactions based-studies have contributed to increase our understanding on plant resistance mechanisms, providing new tools for crop improvement. In the last two decades, RNA interference, a post-transcriptional gene silencing approach, has been used to induce antiviral defenses in plants with the help of genetic engineering technologies. More recently, the new genome editing systems (GES) are revolutionizing the scope of tools available to confer virus resistance in plants. The most explored GES are zinc finger nucleases, transcription activator-like effector nucleases, and clustered regularly interspaced short palindromic repeats/Cas9 endonuclease. GES are engineered to target and introduce mutations, which can be deleterious, via double-strand breaks at specific DNA sequences by the error-prone non-homologous recombination end-joining pathway. Although GES have been engineered to target DNA, recent discoveries of GES targeting ssRNA molecules, including virus genomes, pave the way for further studies programming plant defense against RNA viruses. Most of plant virus species have an RNA genome and at least 784 species have positive ssRNA. Here, we provide a summary of the latest progress in plant antiviral defenses mediated by GES. In addition, we also discuss briefly the GES perspectives in light of the rebooted debate on genetic modified organisms (GMOs) and the current regulatory frame for agricultural products involving the use of such engineering technologies. PMID:28167937

  8. Avian Interferons and Their Antiviral Effectors

    Science.gov (United States)

    Santhakumar, Diwakar; Rubbenstroth, Dennis; Martinez-Sobrido, Luis; Munir, Muhammad

    2017-01-01

    Interferon (IFN) responses, mediated by a myriad of IFN-stimulated genes (ISGs), are the most profound innate immune responses against viruses. Cumulatively, these IFN effectors establish a multilayered antiviral state to safeguard the host against invading viral pathogens. Considerable genetic and functional characterizations of mammalian IFNs and their effectors have been made, and our understanding on the avian IFNs has started to expand. Similar to mammalian counterparts, three types of IFNs have been genetically characterized in most avian species with available annotated genomes. Intriguingly, chickens are capable of mounting potent innate immune responses upon various stimuli in the absence of essential components of IFN pathways including retinoic acid-inducible gene I, IFN regulatory factor 3 (IRF3), and possibility IRF9. Understanding these unique properties of the chicken IFN system would propose valuable targets for the development of potential therapeutics for a broader range of viruses of both veterinary and zoonotic importance. This review outlines recent developments in the roles of avian IFNs and ISGs against viruses and highlights important areas of research toward our understanding of the antiviral functions of IFN effectors against viral infections in birds. PMID:28197148

  9. Avian Interferons and Their Antiviral Effectors.

    Science.gov (United States)

    Santhakumar, Diwakar; Rubbenstroth, Dennis; Martinez-Sobrido, Luis; Munir, Muhammad

    2017-01-01

    Interferon (IFN) responses, mediated by a myriad of IFN-stimulated genes (ISGs), are the most profound innate immune responses against viruses. Cumulatively, these IFN effectors establish a multilayered antiviral state to safeguard the host against invading viral pathogens. Considerable genetic and functional characterizations of mammalian IFNs and their effectors have been made, and our understanding on the avian IFNs has started to expand. Similar to mammalian counterparts, three types of IFNs have been genetically characterized in most avian species with available annotated genomes. Intriguingly, chickens are capable of mounting potent innate immune responses upon various stimuli in the absence of essential components of IFN pathways including retinoic acid-inducible gene I, IFN regulatory factor 3 (IRF3), and possibility IRF9. Understanding these unique properties of the chicken IFN system would propose valuable targets for the development of potential therapeutics for a broader range of viruses of both veterinary and zoonotic importance. This review outlines recent developments in the roles of avian IFNs and ISGs against viruses and highlights important areas of research toward our understanding of the antiviral functions of IFN effectors against viral infections in birds.

  10. Pyruvate Carboxylase Activates the RIG-I-like Receptor-Mediated Antiviral Immune Response by Targeting the MAVS signalosome

    Science.gov (United States)

    Cao, Zhongying; Zhou, Yaqin; Zhu, Shengli; Feng, Jian; Chen, Xueyuan; Liu, Shi; Peng, Nanfang; Yang, Xiaodan; Xu, Gang; Zhu, Ying

    2016-01-01

    When retinoic acid-inducible gene 1 protein (RIG-I)-like receptors sense viral dsRNA in the cytosol, RIG-I and melanoma differentiation-associated gene 5 (MDA5) are recruited to the mitochondria to interact with mitochondrial antiviral signaling protein (MAVS) and initiate antiviral immune responses. In this study, we demonstrate that the biotin-containing enzyme pyruvate carboxylase (PC) plays an essential role in the virus-triggered activation of nuclear factor kappa B (NF-κB) signaling mediated by MAVS. PC contributes to the enhanced production of type I interferons (IFNs) and pro-inflammatory cytokines, and PC knockdown inhibits the virus-triggered innate immune response. In addition, PC shows extensive antiviral activity against RNA viruses, including influenza A virus (IAV), human enterovirus 71 (EV71), and vesicular stomatitis virus (VSV). Furthermore, PC mediates antiviral action by targeting the MAVS signalosome and induces IFNs and pro-inflammatory cytokines by promoting phosphorylation of NF-κB inhibitor-α (IκBα) and the IκB kinase (IKK) complex, as well as NF-κB nuclear translocation, which leads to activation of interferon-stimulated genes (ISGs), including double-stranded RNA-dependent protein kinase (PKR) and myxovirus resistance protein 1 (Mx1). Our findings suggest that PC is an important player in host antiviral signaling. PMID:26906558

  11. Baseline MELD score predicts hepatic decompensation during antiviral therapy in patients with chronic hepatitis C and advanced cirrhosis.

    Directory of Open Access Journals (Sweden)

    Georg Dultz

    Full Text Available BACKGROUND AND AIMS: In patients with advanced liver cirrhosis due to chronic hepatitis C virus (HCV infection antiviral therapy with peginterferon and ribavirin is feasible in selected cases only due to potentially life-threatening side effects. However, predictive factors associated with hepatic decompensation during antiviral therapy are poorly defined. METHODS: In a retrospective cohort study, 68 patients with HCV-associated liver cirrhosis (mean MELD score 9.18 ± 2.72 were treated with peginterferon and ribavirin. Clinical events indicating hepatic decompensation (onset of ascites, hepatic encephalopathy, upper gastrointestinal bleeding, hospitalization as well as laboratory data were recorded at baseline and during a follow up period of 72 weeks after initiation of antiviral therapy. To monitor long term sequelae of end stage liver disease an extended follow up for HCC development, transplantation and death was applied (240 weeks, ± SD 136 weeks. RESULTS: Eighteen patients (26.5% achieved a sustained virologic response. During the observational period a hepatic decompensation was observed in 36.8%. Patients with hepatic decompensation had higher MELD scores (10.84 vs. 8.23, p14, respectively. Baseline MELD score was significantly associated with the risk for transplantation/death (p<0.001. CONCLUSIONS: Our data suggest that the baseline MELD score predicts the risk of hepatic decompensation during antiviral therapy and thus contributes to decision making when antiviral therapy is discussed in HCV patients with advanced liver cirrhosis.

  12. The broad-spectrum antiviral favipiravir protects guinea pigs from lethal Lassa virus infection post-disease onset.

    Science.gov (United States)

    Safronetz, David; Rosenke, Kyle; Westover, Jonna B; Martellaro, Cynthia; Okumura, Atsushi; Furuta, Yousuke; Geisbert, Joan; Saturday, Greg; Komeno, Takashi; Geisbert, Thomas W; Feldmann, Heinz; Gowen, Brian B

    2015-10-12

    With up to 500,000 infections annually, Lassa virus (LASV), the cause of Lassa fever, is one of the most prevalent etiological agents of viral hemorrhagic fever (VHF) in humans. LASV is endemic in several West African countries with sporadic cases and prolonged outbreaks observed most commonly in Sierra Leone, Liberia, Guinea and Nigeria. Additionally several cases of Lassa fever have been imported into North America, Europe and Asia making LASV a global threat to public health. Despite this, currently no approved therapeutic or vaccine exists to treat or prevent LASV infections. Here, using a passaged strain of LASV that is uniformly lethal in Hartley guinea pigs, we demonstrate that favipiravir, a broad-spectrum antiviral agent and leading treatment option for influenza, has potent activity against LASV infection. In this model, once daily treatment with favipiravir significantly reduced viral titers in tissue samples and reduced mortality rates when compared with animals receiving vehicle-only or ribavirin, the current standard of care for Lassa fever. Favipiravir remained highly effective against lethal LASV infection when treatments were initiated nine days post-infection, a time when animals were demonstrating advanced signs of disease. These results support the further preclinical evaluation of favipiravir for Lassa fever and other VHFs.

  13. Beyond RNAi: antiviral defense strategies in Drosophila and mosquito

    NARCIS (Netherlands)

    Merkling, S.H.; Rij, R.P. van

    2013-01-01

    Virus transmission and spread by arthropods is a major economic and public health concern. The ongoing dissemination of arthropod-borne viruses by blood-feeding insects is an important incentive to study antiviral immunity in these animals. RNA interference is a major mechanism for antiviral defense

  14. Induction and suppression of the innate antiviral responses by picornaviruses

    NARCIS (Netherlands)

    Feng, Q.

    2014-01-01

    On the front line of innate antiviral immune reactions is the type I interferon (IFN-α/β) system. IFN-α/β are small signaling molecules that can be produced by virtually all nucleated cells in our body upon virus infections, and induce a so-called “antiviral state” in neighboring cells by activating

  15. Antivirals reduce the formation of key Alzheimer's disease molecules in cell cultures acutely infected with herpes simplex virus type 1.

    Directory of Open Access Journals (Sweden)

    Matthew A Wozniak

    Full Text Available Alzheimer's disease (AD afflicts around 20 million people worldwide and so there is an urgent need for effective treatment. Our research showing that herpes simplex virus type 1 (HSV1 is a risk factor for AD for the brains of people who possess a specific genetic factor and that the virus causes accumulation of key AD proteins (β-amyloid (Aβ and abnormally phosphorylated tau (P-tau, suggests that anti-HSV1 antiviral agents might slow AD progression. However, currently available antiviral agents target HSV1 DNA replication and so might be successful in AD only if Aβ and P-tau accumulation depend on viral DNA replication. Therefore, we investigated firstly the stage(s of the virus replication cycle required for Aβ and P-tau accumulation, and secondly whether antiviral agents prevent these changes using recombinant strains of HSV1 that progress only partly through the replication cycle and antiviral agents that inhibit HSV1 DNA replication. By quantitative immunocytochemistry we demonstrated that entry, fusion and uncoating of HSV1, are insufficient to induce Aβ and P-tau production. We showed also that none of the "immediate early" viral proteins is directly responsible, and that Aβ and P-tau are produced at a subsequent stage of the HSV1 replication cycle. Importantly, the anti-HSV1 antiviral agents acyclovir, penciclovir and foscarnet reduced Aβ and P-tau accumulation, as well as HSV1, with foscarnet being less effective in each case. P-tau accumulation was found to depend on HSV1 DNA replication, whereas Aβ accumulation was not. The antiviral-induced decrease in Aβ is attributable to the reduced number of new viruses, and hence the reduction in viral spread. Since antiviral agents reduce greatly Aβ and P-tau accumulation in HSV1-infected cells, they would be suitable for treating AD with great advantage unlike current AD therapies, only the virus, not the host cell, would be targeted.

  16. Novel Plant-Derived Recombinant Human Interferons with Broad Spectrum Antiviral Activity

    Science.gov (United States)

    2011-10-14

    compared the antiviral activities of more than 1400 plant-derived, hybrid IFNs against three RNA viruses and one DNA virus from four different families...highly pathogenic viruses with varying sensitivities to type I IFN. In particular, the DNA virus , MPXV, was not expected to be as susceptible to the...K.M., Callis, R.T., Stephen, E.L., 1980. Lassa virus infection of rhesus monkeys: pathogenesis and treatment with ribavirin. J. Infect. Dis. 141, 580

  17. Concurrent Chemotherapy and Pulsed High-Intensity Focused Ultrasound Therapy for the Treatment of Unresectable Pancreatic Cancer: Initial Experiences

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jae Young; Choi, Byung Ihn; Ryu, Ji Kon; Kim, Yong Tae; Kim, Se Hyung; Han, Joon Koo [Seoul National University Hospital, Seoul (Korea, Republic of); Hwang, Joo Ha [University of Washington Medical Center, Seattle (United States)

    2011-04-15

    This study was performed to evaluate the potential clinical value of concurrent chemotherapy and pulsed high intensity focused ultrasound (HIFU) therapy (CCHT), as well as the safety of pulsed HIFU, for the treatment of unresectable pancreatic cancer. Twelve patients were treated with HIFU from October 2008 to May 2010, and three of them underwent CCHT as the main treatment (the CCHT group). The overall survival (OS), the time to tumor progression (TTP), the complications and the current performance status in the CCHT and non-CCHT groups were analyzed. Nine patients in the non-CCHT group were evaluated to determine why CCHT could not be performed more than twice. The OS of the three patients in the CCHT group was 26.0, 21.6 and 10.8 months, respectively, from the time of diagnosis. Two of them were alive at the time of preparing this manuscript with an excellent performance status, and one of them underwent a surgical resection one year after the initiation of CCHT. The TTP of the three patients in the CCHT group was 13.4, 11.5 and 9.9 months, respectively. The median OS and TTP of the non-CCHT group were 10.3 months and 4.4 months, respectively. The main reasons why the nine patients of the non-CCHT group failed to undergo CCHT more than twice were as follows: pancreatitis (n = 1), intolerance of the pain during treatment (n = 4), palliative use of HIFU for pain relief (n = 1) and a poor physical condition due to disease progression (n = 3). No major complications were encountered except one case of pancreatitis. This study shows that CCHT is a potentially effective and safe modality for the treatment of unresectable pancreatic cancer

  18. Neurodevelopment and brain growth in classic Menkes disease is influenced by age and symptomatology at initiation of copper treatment.

    Science.gov (United States)

    Kaler, Stephen G

    2014-10-01

    Menkes disease is an X-linked recessive disorder of brain copper metabolism caused by mutations in an essential mammalian copper transport gene, ATP7A. Untreated affected individuals suffer failure to thrive and neurodevelopmental delays that usually commence at 6-8 weeks of age. Death by age three years is typical. While provision of working copies of ATP7A to the brain by viral vectors is a promising strategy under development, the only treatment currently available is subcutaneous copper injections. These can normalize circulating blood levels and may replete brain copper depending on the molecular context, e.g., the severity of ATP7A mutation and potential presence of mosaicism. In this paper, we summarize somatic growth and neurodevelopmental outcomes for 60 subjects enrolled in a recently concluded phase I/II clinical trial of copper histidine for Menkes disease (ClinicalTrials.gov Identifier: NCT00001262). Primary outcomes indicate highly statistically significant improvements in gross motor, fine motor/adaptive, personal-social, and language neurodevelopment in the cohort of subjects who received early treatment prior to onset of symptoms (n=35). Correlating with these findings, quantitative parameters of somatic growth indicated statistically significant greater growth in head circumference for the initially asymptomatic group, whereas weight and height/length at age three years (or at time of death) did not differ significantly. Mortality at age 3 was higher (50%) in subjects older and symptomatic when treatment commenced compared to the asymptomatic group (28.6%). We conclude that early copper histidine for Menkes disease is safe and efficacious, with treatment outcomes influenced by the timing of intervention, and ATP7A mutation.

  19. Implementing nurse-initiated and managed antiretroviral treatment (NIMART in South Africa: a qualitative process evaluation of the STRETCH trial

    Directory of Open Access Journals (Sweden)

    Georgeu Daniella

    2012-07-01

    Full Text Available Abstract Background Task-shifting is promoted widely as a mechanism for expanding antiretroviral treatment (ART access. However, the evidence for nurse-initiated and managed ART (NIMART in Africa is limited, and little is known about the key barriers and enablers to implementing NIMART programmes on a large scale. The STRETCH (Streamlining Tasks and Roles to Expand Treatment and Care for HIV programme was a complex educational and organisational intervention implemented in the Free State Province of South Africa to enable nurses providing primary HIV/AIDS care to expand their roles and include aspects of care and treatment usually provided by physicians. STRETCH used a phased implementation approach and ART treatment guidelines tailored specifically to nurses. The effects of STRETCH on pre-ART mortality, ART provision, and the quality of HIV/ART care were evaluated through a randomised controlled trial. This study was conducted alongside the trial to develop a contextualised understanding of factors affecting the implementation of the programme. Methods This study was a qualitative process evaluation using in-depth interviews and focus group discussions with patients, health workers, health managers, and other key informants as well as observation in clinics. Research questions focused on perceptions of STRETCH, changes in health provider roles, attitudes and patient relationships, and impact of the implementation context on trial outcomes. Data were analysed collaboratively by the research team using thematic analysis. Results NIMART appears to be highly acceptable among nurses, patients, and physicians. Managers and nurses expressed confidence in their ability to deliver ART successfully. This confidence developed slowly and unevenly, through a phased and well-supported approach that guided nurses through training, re-prescription, and initiation. The research also shows that NIMART changes the working and referral relationships between health

  20. Development of ultrafine-grained 1100 aluminum alloy by cryorolling with the optimized initial heat treatment conditions

    Science.gov (United States)

    Zakaria, Siti Aminah; Hussain, Zuhailawati; Seman, Anasyida Abu

    2016-07-01

    The aims of this study to determine the suitable initial heat treatment for 1100 aluminum alloy prior to cryorolling process and the properties of annealed and cryorolled annealed sample. The samples were annealed at different annealing temperature of 200˚C, 250˚C, 300˚C, 350˚C and 400˚C for 2 hours soaking time before cryorolling. The annealing samples then were cryorolled up to 50% thickness reduction after dipping in liquid nitrogen for 30 minutes. The effect of annealing temperature on cryorolled sample was investigated by employing hardness measurements and tensile test. The highest hardness and tensile properties achieved for sample annealed at 250 °C. The entire cryorolled sample showed severely deformed grain which are elongated along and following the rolling direction.

  1. Contacts to general practice and antidepressant treatment initiation after screening for anxiety and depression in patients with heart disease

    DEFF Research Database (Denmark)

    Larsen, Karen Kjær; Vestergaard, Claus Høstrup; Schougaard, Liv Marit Valen;

    2016-01-01

    Introduction Anxiety and depression are found in 20-30% of all persons with heart disease, and depression is known to impact mortality. This paper aimed to describe the effect of systematic screening of this population in terms of use of general practice, psychological therapy and antidepressant...... symptoms had more general practitioner (GP) contact rates than patients without anxiety or depressive symptoms both before and after the screening. Furthermore, patients with depressive symptoms increased their GP contact rate significantly in the first month after the screening, while...... this was not the case for patients with anxiety symptoms. Finally, patients with heart disease and anxiety or depressive symptoms more frequently initiated treatment with antidepressants than patients with heart disease without anxiety or depressive symptoms, whereas therapy sessions with a psychologist were rarely...

  2. The initial treatment of the concept of function in the selected secondary school mathematics textbooks in the US and China

    Science.gov (United States)

    Son, Ji-Won; Hu, Qintong

    2016-05-01

    In order to provide insight into cross-national differences in students' achievement, this study compares the initial treatment of the concept of function sections of Chinese and US textbooks. The number of lessons, contents, and mathematical problems were analyzed. The results show that the US curricula introduce the concept of function one year earlier than the Chinese curriculum and provide strikingly more problems for students to work on. However, the Chinese curriculum emphasizes developing both concepts and procedures and includes more problems that require explanations, visual representations, and problem solving in worked-out examples that may help students formulate multiple solution methods. This result could indicate that instead of the number of problems and early introduction of the concept, the cognitive demands of textbook problems required for student thinking could be one reason for differences in American and Chinese students' performances in international comparative studies. Implications of these findings for curriculum developers, teachers, and researchers are discussed.

  3. Metabolic syndrome before and after initiation of antiretroviral therapy in treatment-naïve HIV-infected individuals

    Science.gov (United States)

    Krishnan, S; Schouten, JT; Atkinson, B; Brown, T; Wohl, D; McComsey, GA; Glesby, MJ; Shikuma, C; Haubrich, R; Tebas, P; Campbell, TB; Jacobson, DL

    2012-01-01

    Background Metabolic syndrome (MetS) is a cluster of risk factors for cardiovascular disease and diabetes, many of which are associated with HIV and antiretroviral therapy (ART). We examined prevalence and incidence of MetS, and risk factors for MetS in ART-naïve HIV-infected individuals starting ART. Methods MetS, defined by the Adult Treatment Panel III criteria, was assessed at and after ART initiation in HIV-infected individuals who enrolled in selected AIDS Clinical Trials Group (ACTG) trials and were followed long-term after these trials as part of the ACTG Longitudinal Linked Randomized Trials cohort. Cox proportional hazards models were used to examine risk factors of incident MetS. Adjusted hazard ratios (aHR) and 95% confidence intervals (CI) are reported. Results At ART initiation, the prevalence of MetS was 20%. After ART initiation, the incidence of MetS was 8.5 per 100 person-years. After adjusting for demographics and body mass index, the risk of MetS was decreased for CD4+ T-cell counts>50 cells/mm3 (aHR = 0.62, 95% CI=0.43 to 0.90 for CD4>500), and the risk was increased for HIV-1 RNA >400 copies/mL (aHR=1.55 (95% CI=1.25 to 1.92) and use of a protease-inhibitor (PI) based regimen (relative to no PI use, aHR=1.25 (95% CI=1.04 to 1.51) for any PI use). Conclusion In HIV-infected individuals on ART, virologic suppression and maintenance of high CD4+ T-cell counts may be potentially modifiable factors that can reduce the risk of MetS. The effect of MetS on the risk of cardiovascular disease and diabetes needs to be evaluated. PMID:22828718

  4. Behavioral health referrals and treatment initiation rates in integrated primary care: a Collaborative Care Research Network study.

    Science.gov (United States)

    Auxier, Andrea; Runyan, Christine; Mullin, Daniel; Mendenhall, Tai; Young, Jessica; Kessler, Rodger

    2012-09-01

    Although the benefits of integrating behavioral health (BH) services into primary care are well established (World Health Organization and World Organization of Family Doctors, 2012; Chiles et al. in Clin Psychol-Sci Pr 6:204-220, 1999; Cummings 1997; O'Donohue et al. 2003; Olfson et al. in Health Aff 18:79-93, 1999; Katon et al. in Ann Intern Med 124:917-925, 2001; Simon et al. in Arch Gen Psychiatry 52:850-856, 1995; Anderson et al. in Diabetes Care 24:1069-1078, 2001; Ciechanowski et al. in Arch Intern Med 160:3278-3285, 2000; Egede et al. in Diabetes Care 25:464-470, 2002), research has focused primarily on describing the types of interventions behavioral health providers (BHPs) employ rather than on reasons for referral, treatment initiation rates, or the patient characteristics that may impact them. This study presents the results of a multisite card study organized by The Collaborative Care Research Network, a subnetwork of the American Academy of Family Physicians' National Research Network devoted to conducting practice-based research focused on the provision of BH and health behavior services within primary care practices. The goals of the study included: (1) identifying the characteristics of patients referred for BH services; (2) codifying reasons for referral and whether patients were treated for the referral; (3) exploring any differences between patients who initiated BH contact and those who did not; and (4) assessing the types and frequency of BH services provided to patients who attended at least one appointment. Of the 200 patients referred to a BHP, 81 % had an initial contact, 71 % of which occurred on the same day. Men and women were equally likely to engage with a BHP although the time between appointments varied by gender. Depression and anxiety were the primary reasons for referral. Practice-based research is a viable strategy for advancing the knowledge about integrated primary care.

  5. The Antiviral Activities and Mechanisms of Marine Polysaccharides: An Overview

    Science.gov (United States)

    Wang, Wei; Wang, Shi-Xin; Guan, Hua-Shi

    2012-01-01

    Recently, the studies on the antiviral activities of marine natural products, especially marine polysaccharides, are attracting more and more attention all over the world. Marine-derived polysaccharides and their lower molecular weight oligosaccharide derivatives have been shown to possess a variety of antiviral activities. This paper will review the recent progress in research on the antiviral activities and the mechanisms of these polysaccharides obtained from marine organisms. In particular, it will provide an update on the antiviral actions of the sulfated polysaccharides derived from marine algae including carrageenans, alginates, and fucans, relating to their structure features and the structure–activity relationships. In addition, the recent findings on the different mechanisms of antiviral actions of marine polysaccharides and their potential for therapeutic application will also be summarized in detail. PMID:23235364

  6. The Antiviral Activities and Mechanisms of Marine Polysaccharides: An Overview

    Directory of Open Access Journals (Sweden)

    Hua-Shi Guan

    2012-12-01

    Full Text Available Recently, the studies on the antiviral activities of marine natural products, especially marine polysaccharides, are attracting more and more attention all over the world. Marine-derived polysaccharides and their lower molecular weight oligosaccharide derivatives have been shown to possess a variety of antiviral activities. This paper will review the recent progress in research on the antiviral activities and the mechanisms of these polysaccharides obtained from marine organisms. In particular, it will provide an update on the antiviral actions of the sulfated polysaccharides derived from marine algae including carrageenans, alginates, and fucans, relating to their structure features and the structure–activity relationships. In addition, the recent findings on the different mechanisms of antiviral actions of marine polysaccharides and their potential for therapeutic application will also be summarized in detail.

  7. Change in serum 25-hydroxyvitamin D with antiretroviral treatment initiation and nutritional intervention in HIV-positive adults

    DEFF Research Database (Denmark)

    Yilma, Daniel; Kæstel, Pernille; Olsen, Mette F;

    2016-01-01

    Low vitamin D level in HIV-positive persons has been associated with disease progression. We compared the levels of serum 25-hydroxyvitamin D (25(OH)D) in HIV-positive and HIV-negative persons, and investigated the role of nutritional supplementation and antiretroviral treatment (ART) on serum 25...... daily allowance of vitamin D (10 μg/200 g). The level of serum 25(OH)D before nutritional intervention and ART initiation was compared with serum 25(OH)D of HIV-negative individuals. A total of 348 HIV-positive and 100 HIV-negative persons were recruited. The median baseline serum 25(OH)D level......-supplemented group had a 10·8 (95 % CI 7·8, 13·9) nmol/l decrease in serum 25(OH)D level after 3 months of ART. Nutritional supplementation that contained vitamin D prevented a reduction in serum 25(OH)D levels in HIV-positive persons initiating ART. Vitamin D replenishment may be needed to prevent reduction...

  8. Reduction in plasma cell proliferation after initial therapy in newly diagnosed multiple myeloma measures treatment response and predicts improved survival.

    Science.gov (United States)

    Larsen, Jeremy T; Chee, Cheng E; Lust, John A; Greipp, Philip R; Rajkumar, S Vincent

    2011-09-08

    Standard myeloma treatment response criteria are determined principally by changes in the monoclonal protein. Reduction in the size of the proliferative component of malignant plasma cells may be an additional metric of assessing response to therapy. We retrospectively analyzed 176 patients with newly diagnosed myeloma with a measurable plasma cell labeling index (PCLI) at diagnosis and repeat measurement 4 months after initiation of therapy. PCLI response was defined as a ≥ 60% reduction. Baseline PCLI is an independent prognostic factor; therefore, we categorized patients into 3 groups: PCLI ≥ 3% (high), ≥ 1% (intermediate), and compared with 29 months in nonresponders (P = .02). Improved median overall survival with PCLI response occurred in the high initial PCLI group (28 vs 7 months; P = .003) and intermediate group (64 vs 24 months; P = .002). The application of PCLI response and serum M-spike response together provided further prognostic information. On multivariate analysis, the prognostic value of PCLI response was independent of β(2)-microglobulin, elevated creatinine, serum M-spike response, and baseline PCLI. We conclude that a significant reduction in plasma cell proliferation in patients with newly diagnosed myeloma is an important predictor of survival.

  9. [Successful treatment of HIV-associated chronic inflammatory demyelinating polyneuropathy by early initiation of highly active anti-retroviral therapy].

    Science.gov (United States)

    Kume, Kodai; Ikeda, Kazuyo; Kamada, Masaki; Touge, Tetsuo; Deguchi, Kazushi; Masaki, Tsutomu

    2013-01-01

    A 47-year-old man with HIV infection presented with lower leg dominant dysesthesia, muscle weakness and sensory ataxia of 3 month's duration. Nerve conduction studies (NCS) showed demyelination change in the median and tibial nerves and sensory nerve action potential (SNAP) in the sural nerve was not evoked. Somatosensory evoked potential (SEP) showed the delayed N9 latency. Diagnose of HIV-associated chronic inflammatory demyelinating polyneuropathy (CIDP) was made. Although the CD4 lymphocyte counts were relatively preserved (466/μl), highly active anti-retroviral therapy (HAART) was started according to a new guideline for the use of antiretroviral agents in HIV-1-infected adults and adolescents recommending early initiation of treatment. After six months, HIV1-RNA was not detected and the CD4 lymphocyte counts showed a recovering trend (585/μl). His symptoms had disappeared, except for dysesthesia in the tip of a toe. Repeated NCS demonstrated full recovery from the demyelination and appearance of SNAP in the sural nerve. The improvement of his symptoms and NCS findings has been maintained for two years. Although effectiveness of immunotherapies such as oral prednisone, high-dose immunoglobulins and plasmapheresis have been reported in HIV-associated CIDP, early initiation of HAART may be also important for favorable prognosis in HIV-associated CIDP.

  10. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in the treatment of peritoneal carcinomatosis: initial experience in Oaxaca, Mexico.

    Science.gov (United States)

    García-Matus, Rolando; Hernández-Hernández, Carlos Alberto; Leyva-García, Omar; Vásquez-Ciriaco, Sergio; Flores-Ayala, Guillermo; Navarro-Hernández, Quetzalli; Pérez-Bustamante, Gerardo; Valencia-Mijares, Norma Miriam; Esquivel, Jesus

    2012-09-01

    Peritoneal carcinomatosis (PC) has been traditionally considered a terminal disease with median survivals reported in the literature of 6 to 12 months. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) are playing an ever increasing role in the treatment of these patients. Excellent results have been achieved in well-selected patients but there is a very steep learning curve when starting a new program. A program for peritoneal surface malignancies in which patients with PC of gastrointestinal or gynecological origin were treated using multimodality therapy with combinations of systemic therapy, cytoreductive surgery (CRS), and HIPEC was initiated in December 2007 at "Hospital Regional de Alta Especialidad de Oaxaca," Mexico. We present the results of our initial experience. From December 2007 to February 2011, 26 patients were treated with CRS and HIPEC. There were 21 female patients. Most common indication (46%) was recurrent ovarian cancer. Mean duration of surgery was 260 minutes. Mean Peritoneal Cancer Index was 9. Twenty-three (88.5%) patients had a complete cytoreduction. Major morbidity and mortality rates were 19.5 and 3.8 per cent, respectively. Mean hospital stay was 8 days. At a mean follow-up of 20 months, median survival has not been reached. Rigorous preoperative workup, strict selection criteria, and mentoring from an experienced cytoreductive surgeon are mandatory and extremely important when starting a center for PC.

  11. Transcriptional analysis of antiviral small molecule therapeutics as agonists of the RLR pathway

    Directory of Open Access Journals (Sweden)

    R.R. Green

    2016-03-01

    Full Text Available The recognition of pathogen associated molecular patterns (PAMPs by pattern recognition receptors (PRR during viral infection initiates the induction of antiviral signaling pathways, including activation of the Interferon Regulator Factor 3 (IRF3. We identified small molecule compounds that activate IRF3 through MAVS, thereby inhibiting infection by viruses of the families Flaviviridae (West Nile virus, dengue virus and hepatitis C virus, Filoviridae (Ebola virus, Orthomyxoviridae (influenza A virus, Arenaviridae (Lassa virus and Paramyxoviridae (respiratory syncytial virus, Nipah virus (1. In this study, we tested a lead compound along with medicinal chemistry-derived analogs to compare the gene transcriptional profiles induced by these molecules to that of other known MAVS-dependent IRF3 agonists. Transcriptional analysis of these small molecules revealed the induction of specific antiviral genes and identified a novel module of host driven immune regulated genes that suppress infection of a range of RNA viruses. Microarray data can be found in Gene Expression Omnibus (GSE74047.

  12. Arbidol: a broad-spectrum antiviral that inhibits acute and chronic HCV infection

    Directory of Open Access Journals (Sweden)

    Pécheur Eve-Isabelle

    2006-07-01

    Full Text Available Abstract Arbidol (ARB is an antiviral compound that was originally proven effective for treatment of influenza and several other respiratory viral infections. The broad spectrum of ARB anti-viral activity led us to evaluate its effect on hepatitis C virus (HCV infection and replication in cell culture. Long-term ARB treatment of Huh7 cells chronically replicating a genomic length genotype 1b replicon resulted in sustained reduction of viral RNA and protein expression, and eventually cured HCV infected cells. Pre-treatment of human hepatoma Huh7.5.1 cells with 15 μM ARB for 24 to 48 hours inhibited acute infection with JFH-1 virus by up to 1000-fold. The inhibitory effect of ARB on HCV was not due to generalized cytotoxicity, nor to augmentation of IFN antiviral signaling pathways, but involved impaired virus-mediated membrane fusion. ARB's affinity for membranes may inhibit several aspects of the HCV lifecycle that are membrane-dependent.

  13. Lower liver cancer risk with antiviral therapy in chronic hepatitis B patients with normal to minimally elevated ALT and no cirrhosis

    Science.gov (United States)

    Hoang, Joseph K.; Yang, Hwai-I; Le, An; Nguyen, Nghia H.; Lin, Derek; Vu, Vinh D.; Chaung, Kevin; Nguyen, Vincent; Trinh, Huy N.; Li, Jiayi; Zhang, Jian Q.; Chen, Chien-Jen; Nguyen, Mindie H.

    2016-01-01

    Abstract For chronic hepatitis B (CHB), alanine aminotransferase (ALT) ≥2 × upper limit of normal (ULN) is often used as a major criteria to initiate treatment in absence of cirrhosis, though patients with lower ALT may not be free from future risk of hepatocellular carcinoma (HCC). We aimed to examine the effect of antiviral therapy on HCC incidence based on ALT levels. We performed a retrospective study on 3665 patients consisting of United States and Taiwanese REVEAL-HBV cohort who were consecutive, treatment-naïve, noncirrhotic CHB patients aged ≥40 years. Patients were categorized by ALT cutoffs (≥2 × ULN vs <2 × ULN) and subgrouped by treatment status. Kaplan–Meier and Cox proportional hazards models were used to calculate cumulative incidence and hazard ratio (HR) of HCC adjusting for REACH-B scores. A total of 202 patients developed HCC. Antiviral treatment significantly reduced HCC risk: HR 0.24, 95% confidence interval 0.10–0.58; P = 0.001. HCC incidence per 100,000 person-years was significantly higher in untreated versus treated patients, even for those with ALT < 2 × ULN: 314.46 versus 0 per 100,000 person-years, P = 0.0042. For patients with Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) ≥ 2000 IU/mL, the number-needed-to-treat (NNT) were 15 and 14 to prevent 1 incident HCC at year 10 for patients with ALT < 2 × ULN and ≥2 × ULN, respectively. After adjustment by REACH-B score, antiviral treatment significantly decreased HCC incidence even in patients with ALT < 2 × ULN. NNT to prevent 1 incident HCC after 10 years of therapy was low (14–15) in patients with mildly elevated HBV DNA ≥ 2000 IU/mL regardless of ALT levels. PMID:27495067

  14. IFNβ/TNFα synergism induces a non-canonical STAT2/IRF9-dependent pathway triggering a novel DUOX2 NADPH Oxidase-mediated airway antiviral response

    Institute of Scientific and Technical Information of China (English)

    Karin Fink; Lydie Martin; Esperance Mukawera; Stéfany Chartier; Xavier De Deken; Emmanuelle Brochiero; Fran(c)oise Miot

    2013-01-01

    Airway epithelial cells are key initial innate immune responders in the fight against respiratory viruses,primarily via the secretion of antiviral and proinflammatory cytokines that act in an autocrine/paracrine fashion to trigger the establishment of an antiviral state.It is currently thought that the early antiviral state in airway epithelial cells primarily relies on IFNβ secretion and the subsequent activation of the interferon-stimulated gene factor 3 (ISGF3) transcription factor complex,composed of STAT1,STAT2 and IRF9,which regulates the expression of a panoply of interferon-stimulated genes encoding proteins with antiviral activities.However,the specific pathways engaged by the synergistic action of different cytokines during viral infections,and the resulting physiological outcomes are still ill-defined.Here,we unveil a novel delayed antiviral response in the airways,which is initiated by the synergistic autocrine/paracrine action of IFNβ and TNFα,and signals through a non-canonical STAT2-and IRF9-dependent,but STAT1-independent cascade.This pathway ultimately leads to the late induction of the DUOX2 NADPH oxidase expression.Importantly,our study uncovers that the development of the antiviral state relies on DUOX2-dependent H2O2 production.Key antiviral pathways are often targeted by evasion strategies evolved by various pathogenic viruses.In this regard,the importance of the novel DUOX2-dependent antiviral pathway is further underlined by the observation that the human respiratory syncytial virus is able to subvert DUOX2 induction.

  15. The combined use of alphavirus replicons and pseudoinfectious particles for the discovery of antivirals derived from natural products.

    Science.gov (United States)

    Delekta, Phillip C; Raveh, Avi; Larsen, Martha J; Schultz, Pamela J; Tamayo-Castillo, Giselle; Sherman, David H; Miller, David J

    2015-06-01

    Alphaviruses are a prominent class of reemergent pathogens due to their globally expanding ranges, potential for lethality, and possible use as bioweapons. The absence of effective treatments for alphaviruses highlights the need for innovative strategies to identify antiviral agents. Primary screens that use noninfectious self-replicating RNAs, termed replicons, have been used to identify potential antiviral compounds for alphaviruses. Only inhibitors of viral genome replication, however, will be identified using replicons, which excludes many other druggable steps in the viral life cycle. To address this limitation, we developed a western equine encephalitis virus pseudoinfectious particle system that reproduces several crucial viral life cycle steps in addition to genome replication. We used this system to screen a library containing ~26,000 extracts derived from marine microbes, and we identified multiple bacterial strains that produce compounds with potential antiviral activity. We subsequently used pseudoinfectious particle and replicon assays in parallel to counterscreen candidate extracts, and followed antiviral activity during biochemical fractionation and purification to differentiate between inhibitors of viral entry and genome replication. This novel process led to the isolation of a known alphavirus entry inhibitor, bafilomycin, thereby validating the approach for the screening and identification of potential antiviral compounds.

  16. Epimedium koreanum Nakai Water Extract Exhibits Antiviral Activity against Porcine Epidermic Diarrhea Virus In Vitro and In Vivo

    Directory of Open Access Journals (Sweden)

    Won-Kyung Cho

    2012-01-01

    Full Text Available Porcine epidemic diarrhea virus (PEDV causes diarrhea of pigs age-independently and death of young piglets, resulting in economic loss of porcine industry. We have screened 333 natural oriental herbal medicines to search for new antiviral candidates against PEDV. We found that two herbal extracts, KIOM 198 and KIOM 124, contain significant anti-PED viral effect. KIOM 198 and KIOM 124 were identified as Epimedium koreanum Nakai and Lonicera japonica Thunberg, respectively. The further plaque and CPE inhibition assay in vitro showed that KIOM 198 has much stronger antiviral activity than KIOM 124. Additionally, KIOM 198 exhibited a similar extent of antiviral effect against other subtypes of Corona virus such as sm98 and TGE viruses. Cytotoxicity results showed that KIOM 198 is nontoxic on the cells and suggest that it can be delivered safely for therapy. Furthermore, when we orally administered KIOM 198 to piglets and then infected them with PEDV, the piglets did not show any disease symptoms like diarrhea and biopsy results showed clean intestine, whereas control pigs without KIOM 198 treatment exhibited PED-related severe symptoms. These results imply that KIOM 198 contains strong antiviral activity and has a potential to be developed as an antiviral phytomedicine to treat PEDV-related diseases in pigs.

  17. Thieno[2,3-b]pyridine derivatives: a new class of antiviral drugs against Mayaro virus.

    Science.gov (United States)

    Amorim, Raquel; de Meneses, Marcelo Damião Ferreira; Borges, Julio Cesar; da Silva Pinheiro, Luiz Carlos; Caldas, Lucio Ayres; Cirne-Santos, Claudio Cesar; de Mello, Marcos Vinícius Palmeira; de Souza, Alessandra Mendonça Teles; Castro, Helena Carla; de Palmer Paixão, Izabel Christina Nunes; Campos, Renata de Mendonça; Bergmann, Ingrid E; Malirat, Viviana; Bernardino, Alice Maria Rolim; Rebello, Moacyr Alcoforado; Ferreira, Davis Fernandes

    2017-02-17

    Mayaro virus (MAYV) is an arthropod-borne virus and a member of the family Togaviridae, genus Alphavirus. Its infection leads to an acute illness accompanied by long-lasting arthralgia. To date, there are no antiviral drugs or vaccines against infection with MAYV and resources for the prevention or treatment of other alphaviruses are very limited. MAYV has served as a model to study the antiviral potential of several substances on alphavirus replication. In this work we evaluated the antiviral effect of seven new derivatives of thieno[2,3-b]pyridine against MAYV replication in a mammalian cell line. All derivatives were able to reduce viral production effectively at concentrations that were non-toxic for Vero cells. Molecular modeling assays predicted low toxicity risk and good oral bioavailability of the substances in humans. One of the molecules, selected for further study, demonstrated a strong anti-MAYV effect at early stages of replication, as it protected pre-treated cells and also during the late stages, affecting virus morphogenesis. This study is the first to demonstrate the antiviral effect of thienopyridine derivatives on MAYV replication in vitro, suggesting the potential application of these substances as antiviral molecules against alphaviruses. Additional in vivo research will be needed to expand the putative therapeutic applications.

  18. A Robotic Exoskeleton for Treatment of Crouch Gait in Children with Cerebral Palsy: Design and Initial Application.

    Science.gov (United States)

    Lerner, Zachary; Damiano, Diane; Park, Hyung-Soon; Gravunder, Andrew; Bulea, Thomas

    2016-07-27

    Crouch gait, a pathological pattern of walking characterized by excessive knee flexion, is one of the most common gait disorders observed in children with cerebral palsy (CP). Effective treatment of crouch during childhood is critical to maintain mobility into adulthood, yet current interventions do not adequately alleviate crouch in most individuals. Powered exoskeletons provide an untapped opportunity for intervention. The multiple contributors to crouch, including spasticity, contracture, muscle weakness, and poor motor control make design and control of such devices challenging in this population. To our knowledge, no evidence exists regarding the feasibility or efficacy of utilizing motorized assistance to alleviate knee flexion in crouch gait. Here, we present the design of and first results from a powered exoskeleton for extension assistance as a treatment for crouch gait in children with CP. Our exoskeleton, based on the architecture of a knee-ankle-foot orthosis, is lightweight (3.2 kg) and modular. On board sensors enable knee extension assistance to be provided during distinct phases of the gait cycle. We tested our device on one 6 year old male participant with spastic diplegia from CP. Our results show that the powered exoskeleton improved knee extension during stance by 18.1° while total knee range of motion improved 21.0°. Importantly, we observed no significant decrease in knee extensor muscle activity, indicating the user did not rely solely on the exoskeleton to extend the limb. These results establish the initial feasibility of robotic exoskeletons for treatment of crouch and provide impetus for continued investigation of these devices with the aim of deployment for long term gait training in this population.

  19. Real-time PCR detection of some markers of liver function after antiviral treatment of hepatitis B%实时荧光定量PCR监测乙肝抗病毒治疗后部分肝功指标的研究

    Institute of Scientific and Technical Information of China (English)

    张红; 施鑫鹤; 杨海珍; 尤崇革; 李光迪

    2009-01-01

    Objective To sereen new monitoring markers for antiviral treatment of hepatitis B,provide more information for the clinic.Methods HBV DNA copies in serum of 87 patients with chronic hepatitis B were detected by applying Roche LightCyeler RT-PCR system,while serum adenosine deaminase(ADA),prealbumin(PA),alpha fucosidase(AFU)and total bile acid(TBA)were measured with Hitachi 7600 automatic biochemical analyzer(velocity assay and immunoturbidimetry).Results Based on the viral load detected,all patients were divided into three groups;group A(103~104 copies/mL);group B(105~106 copies/mL)and group C(>107 copies/mL).The serum levels of ADA,PA,AFU and TBA were all significantly higher in the three groups than those in healthy control group(P<0.01 or P<0.05).Compared with that in group A and gropu C,PA level was cvidently lower and TBA was markedly higher in group B(both P<0.01).No statistical differences in other indices were found among the three groups(P>0.05).Conclusion ADA,PA,AFU and TBA may be used as sensitive markers for antiviral treatment of hepatitis B,especially for patients of group B,combined detection of these markers contributes to clinical diagnosis and treatment of hepatitis B.%目的 筛选乙肝抗病毒治疗监控新指标,为临床提供更多的信息,满足临床需要.方法 对临床确诊的87例慢性乙肝患者使用罗氏Lightcycler实时荧光定量PCR仪检测其血清病毒拷贝数,并以乙肝病毒载量为标准,分为高、中、低组进行研究;用速率法和免疫比浊法借助日立7600型全自动生化分析仪检测患者血清腺苷脱氨酶(adenosinedeaminase,ADA)、前清蛋白(prcalbumin,PA)、a-L-岩藻糖苷酶(alpha fucosidase,AFU)、总胆汁酸(total bile acid,TBA).结果 使用实时荧光定量PCR仪检测慢性乙肝患者血清巾的病毒拷贝数,据此可将患者血清HBV DNA检测结果分为A、B、C组,A组:103~104 copies/mL;B组:105~106 copies/mL;C组:>107 copics/mL;分别检测ADA

  20. Antifungal and antiviral products of marine organisms.

    Science.gov (United States)

    Cheung, Randy Chi Fai; Wong, Jack Ho; Pan, Wen Liang; Chan, Yau Sang; Yin, Cui Ming; Dan, Xiu Li; Wang, He Xiang; Fang, Evandro Fei; Lam, Sze Kwan; Ngai, Patrick Hung Kui; Xia, Li Xin; Liu, Fang; Ye, Xiu Yun; Zhang, Guo Qing; Liu, Qing Hong; Sha, Ou; Lin, Peng; Ki, Chan; Bekhit, Adnan A; Bekhit, Alaa El-Din; Wan, David Chi Cheong; Ye, Xiu Juan; Xia, Jiang; Ng, Tzi Bun

    2014-04-01

    Marine organisms including bacteria, fungi, algae, sponges, echinoderms, mollusks, and cephalochordates produce a variety of products with antifungal activity including bacterial chitinases, lipopeptides, and lactones; fungal (-)-sclerotiorin and peptaibols, purpurides B and C, berkedrimane B and purpuride; algal gambieric acids A and B, phlorotannins; 3,5-dibromo-2-(3,5-dibromo-2-methoxyphenoxy)phenol, spongistatin 1, eurysterols A and B, nortetillapyrone, bromotyrosine alkaloids, bis-indole alkaloid, ageloxime B and (-)-ageloxime D, haliscosamine, hamigeran G, hippolachnin A from sponges; echinoderm triterpene glycosides and alkene sulfates; molluscan kahalalide F and a 1485-Da peptide with a sequence SRSELIVHQR; and cepalochordate chitotriosidase and a 5026.9-Da antifungal peptide. The antiviral compounds from marine organisms include bacterial polysaccharide and furan-2-yl acetate; fungal macrolide, purpurester A, purpurquinone B, isoindolone derivatives, alterporriol Q, tetrahydroaltersolanol C and asperterrestide A, algal diterpenes, xylogalactofucan, alginic acid, glycolipid sulfoquinovosyldiacylglycerol, sulfated polysaccharide p-KG03, meroditerpenoids, methyl ester derivative of vatomaric acid, lectins, polysaccharides, tannins, cnidarian zoanthoxanthin alkaloids, norditerpenoid and capilloquinol; crustacean antilipopolysaccharide factors, molluscan hemocyanin; echinoderm triterpenoid glycosides; tunicate didemnin B, tamandarins A and B and; tilapia hepcidin 1-5 (TH 1-5), seabream SauMx1, SauMx2, and SauMx3, and orange-spotted grouper β-defensin. Although the mechanisms of antifungal and antiviral activities of only some of the aforementioned compounds have been elucidated, the possibility to use those known to have distinctly different mechanisms, good bioavailability, and minimal toxicity in combination therapy remains to be investigated. It is also worthwhile to test the marine antimicrobials for possible synergism with existing drugs. The prospects of

  1. Tolerance and antiviral effects of high-dose interferon-alpha B/D in patients with chronic hepatitis B

    NARCIS (Netherlands)

    Rasch, MC; Schellekens, H; van Dijck, CMM; Haagsma, EB; Michielsen, PP; van Buuren, AHJAM; Stotter, H; van Hattum, J

    1998-01-01

    A novel recombinant interferon-alpha B/D hybrid was applied to assess tolerability, antiviral effect, and biological activity in chronic hepatitis B. The study was designed as an open nonrandomized trial. Treatment comprised a two-week run-in phase with 16 MU three times a week followed by 14 weeks

  2. Antiviral therapy for chronic hepatitis C in patients with inherited bleeding disorders : an international, multicenter cohort study

    NARCIS (Netherlands)

    Posthouwer, D.; Yee, T. T.; Makris, M.; Griffioen, A.; van Veen, J. J.; Mauser-Bunschoten, E. P.

    2007-01-01

    Background: Hepatitis C is a major co-morbidity in patients with hemophilia. However, there is little information on the efficacy of antiviral therapy and long-term follow-up after treatment. Objectives: To assess the effect of interferon-based (IFN-based) therapy on hepatitis C virus (HCV) eradicat

  3. Atividade antiviral de Musa acuminata Colla, Musaceae Antiviral activity of Musa acuminata Colla, Musaceae

    Directory of Open Access Journals (Sweden)

    Fernanda Otaviano Martins

    2009-09-01

    Full Text Available O presente trabalho avalia a atividade antiviral de extratos e frações de Musa acuminata Colla, Musaceae, coletada em duas regiões do Estado do Rio de Janeiro (Petrópolis e Santo Antônio de Pádua. As inflorescências de M. acuminata apresentaram excelente atividade para os dois vírus avaliados: herpesvírus simples humano tipo 1 e herpesvírus simples humano tipo 2, ambos resistentes ao Aciclovir. Os resultados indicam que os extratos de M. acuminata testados podem constituir alvo potencial para uso em terapias antivirais.This study evaluates the antiviral activity of extracts and fractions of Musa acuminata Colla collected in two regions of Rio de Janeiro State (Petrópolis and Santo Antônio de Pádua. The inflorescences of M. acuminata showed excellent activity for the two virus evaluated: simple human herpesvirus type 1 and simple human herpesvirus type 2, both resistant to Acyclovir. The results indicate that the tested extracts of M. acuminata can be potential target for use in antiviral therapy.

  4. Initial antibiotic treatment for acute simple appendicitis in children is safe: Short-term results from a multicenter, prospective cohort study

    NARCIS (Netherlands)

    Gorter, R.R.; Lee, J.H. van der; Cense, H.A.; Kneepkens, C.M.; Wijnen, M.H.W.A.; Hof, K.H. In 't; Offringa, M.; Heij, H.A.

    2015-01-01

    BACKGROUND: Initial antibiotic treatment for acute appendicitis has been shown to be safe in adults; so far, not much is known about the safety and efficacy of this treatment in children. The aims of this study were to investigate the feasibility of a randomized controlled trial (RCT) evaluating ini

  5. Poor guideline adherence in the initiation of antidepressant treatment in children and adolescents in the Netherlands : choice of antidepressant and dose

    NARCIS (Netherlands)

    de Vries, Ymkje Anna; de Jonge, Peter; Kalverdijk, Luuk; Bos, Jens H. J.; Schuiling-Veninga, Catharina C. M.; Hak, Eelko

    2016-01-01

    The Dutch guideline for the treatment of depression in young people recommends initiating antidepressant treatment with fluoxetine, as the evidence for its efficacy is strongest and the risk of suicidality may be lower than with other antidepressants. Furthermore, low starting doses are recommended.

  6. Valacyclovir in the treatment of acute retinal necrosis

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    Taylor Simon RJ

    2012-09-01

    Full Text Available Abstract Background To report the outcome of oral valacyclovir as the sole antiviral therapy for patients with acute retinal necrosis (ARN. Methods This study reports a retrospective, interventional case series of nine consecutive patients with ten eyes with newly diagnosed ARN treated with oral valacyclovir as the sole antiviral agent. Eight patients received oral valacyclovir 2 g tid (Valtrex, GlaxoSmithKline and one patient with impaired renal function received oral 1 g tid. The main outcome measures were response to treatment, time to initial response to treatment, time to complete resolution of retinitis, best corrected visual acuity (BCVA at final follow-up, retinal detachment and development of recurrent or second eye disease. Results Retinitis resolved in ten of ten (100% affected eyes. The median time to initial detectable response was seven days and the median time to complete resolution was 21 days. A final BCVA of 20/40 or better was achieved in 6/10 (60% of eyes. 3/10 eyes (30% developed a retinal detachment. No patients developed either disease reactivation or second eye involvement over the course of the study (mean follow up 31 weeks, range 7 to 104 weeks. Conclusions Treatment with oral valacyclovir as the sole antiviral therapy resulted in complete resolution of retinitis. Final BCVA and retinal detachment rate were comparable with previously reported outcomes for intravenous acyclovir.

  7. Deep venous thrombosis and pulmonary embolism. Part 1. Initial treatment: usually a low-molecular-weight heparin.

    Science.gov (United States)

    2013-04-01

    anticoagulant therapy reduced mortality or recurrences after pulmonary embolism. In the 5 trials that included patients with massive pulmonary embolism, thrombolytic therapy appeared to reduce mortality by about one-half (6% versus 13%). This difference is noteworthy, even if it did not reach the usual threshold of statistical significance. The results of the 6 trials involving patients with deep venous thrombosis, and those of 2 trials and 8 cohort studies in patients with pulmonary embolism at low risk of complications, suggest that outpatient management is acceptable in some cases. Clinical practice guidelines largely agree on the use of LMWH or fondaparinux as initial therapy for most patients with deep venous thrombosis or pulmonary embolism. Unfractionated heparin is generally recommended for patients with renal failure. Thrombolysis is recommended for massive pulmonary embolism and, in some guidelines, for iliofemoral venous thrombosis. In practice, initial treatment of deep venous thrombosis and pulmonary embolism should be based on LMWH in patients without renal failure. Thrombolytic agents may be useful in case of massive pulmonary embolism, but more evaluation is needed. Bleeding and heparin thrombocytopenia are the main adverse effects of these treatments.

  8. Milnacipran treatment and potential biomarkers in depressed patients following an initial SSRI treatment failure: a prospective, open-label, 24-week study

    Directory of Open Access Journals (Sweden)

    Hashimoto T

    2015-12-01

    Full Text Available Tasuku Hashimoto,1,2 Daiji Sakurai,1 Yasunori Oda,1 Tadashi Hasegawa,3 Nobuhisa Kanahara,4 Tsuyoshi Sasaki,3 Hideki Komatsu,3,5 Junpei Takahashi,1,5 Takahiro Oiwa,6 Yoshimoto Sekine,4,5 Hiroyuki Watanabe,1 Masaomi Iyo1,3 1Department of Psychiatry, Chiba University Graduate School of Medicine, 2Sodegaura Satsukidai Hospital, 3Department of Psychiatry, Chiba University Hospital, 4Division of Medical Treatment and Rehabilitation, Centre for Forensic Mental Health, Chiba University, 5Choshi Kokoro Clinic, 6Mobara Shinkeika Hospital, Chiba, Japan Background: We assessed the effect of switching patients with major depressive disorder to milnacipran following an initial selective serotonin reuptake inhibitor treatment failure, and explored potential biomarkers in their blood.Methods: We conducted a prospective, open-label, 24-week trial. Depression was assessed with the 17-item Hamilton Depression Rating Scale. Patients showing a ≥50% reduction in Hamilton Depression Rating Scale scores from baseline to final visit were considered responders. Regarding adverse effects (AEs, moderate-to-severe AEs were specifically identified as effects that required any medical treatment or that induced treatment withdrawals. We also measured blood levels of various molecules including inflammatory cytokines.Results: Of the 30 participants who enrolled, 17 completed this study. The responder rate was 30% (n=10. Baseline serum levels of interleukin-6 (Z=-2.155; P=0.031 and interleukin-8 (Z=-2.616; P=0.009 were significantly higher when moderate-to-severe AEs were present (n=13 patients with moderate-to-severe AEs. Serum levels of macrophage inflammatory protein-1β showed a significant continuous decrease from the baseline level (Friedman’s test: χ2=23.9, df=4, P<0.001 only in non-responders.Conclusion: These results demonstrate that serum levels of interleukin-6, interleukin-8, and macrophage inflammatory protein-1β as potential blood biomarkers could be utilized

  9. Management of Antiviral Induced Anemia in HCV Infected Patients

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    Mitra Ranjbar

    2005-03-01

    west. Semin Liver Dis. 1995; 15:5-142. Alter HJ, Locarnini SA. Epidemiology of hepatitis C in the east. Semin Liver Dis. 1995; 15:15-323. Seeff LB. Natural history of chronic hepatitis C. Hepatology 2002; 36:S30-S344. Manns MP, Mc Hutchison JG, Gordon SC, et al. Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomized trial. Lancet. 2001; 358:958-655. Fried MW, Shiffman ML, Reddy KR, et al. Peginterferon alfa-2a plus ribavirin for chronic hepatitis C. N Engl J Med. 2002; 347:975-826. PEG-Intron (pegylated interferon alfa-2b package insert. Kenilworth, NJ: Schering-Plough Corporation; October 20037. Gaeta GB, Precone DF, Felaco FM et al., Premature discontinuation of interferon plus ribavirin for advers effects: a multicentre survey in “real world” patients with chronic hepatitis C. Aliment Pharmacol Ther. 2002; 16:1633-98. Dieterich DT, Spivak JL. Hematologic disorders associated with hepatitis C virus infection and their management. Clin Infect Dis. 2002; 185:S128-S1379. Pawlotsky, JM, Dahari, H, Neumann, AU, et al. Antiviral action of ribavirin in chronic hepatitis C. Gastroenterology 2004; 126:70310. ChemelIo, L,Cavalletto, L, Bernardinello, E, et al. The effect of interferon alfa and ribavirin combination therapy in naive patients with chronic hepatitis C. J Hepatol 1995;23 Suppl 2:811. Lai, MY, Kao, JH, Yang, PM,et al. Long-term efficacy of ribavirin plus interferon alfa in the treatment of chronic hepatitis C. Gastroenterology 1996; 111: 130712. Reichard, O, Norkrans, G, Fryden, A, et al. Randomized, double-blind, placebo-controlled trial of interferon alfa-2b with and without ribavirin for chronic hepatitis C. Lancet 1998; 351:8313. Bodenheimer HC Jr, Lindsay KL, Davis GL, LewiS JH, Thung SN, Seeff LB. Tolerance and efficacy of oral ribavirin treatment of chronic hepatitis C: a multicenter trial. Hepatology. 1997; 26:473-714. McHutchison JG, Manns M, Patel K, et al

  10. The initial feasibility of a computer-based motivational intervention for adherence for youth newly recommended to start antiretroviral treatment.

    Science.gov (United States)

    Outlaw, Angulique Y; Naar-King, Sylvie; Tanney, Mary; Belzer, Marvin E; Aagenes, Anna; Parsons, Jeffrey T; Merlo, Lisa J

    2014-01-01

    Young people represent the largest number of new HIV infections, thus youth living with HIV (YLH) are likely to be the largest group to initiate antiretroviral treatment (ART). Adherence patterns for behaviorally infected YLH are not adequate to effectively manage the disease; therefore, novel interventions are needed to improve medication adherence. The purpose of the current study, which will precede a randomized controlled trial, was to assess the initial feasibility of an individually tailored computer-based two-session interactive motivational interviewing (MI) intervention for YLH newly recommended to start ART. Intervention development occurred in collaboration with three youth advisory groups. Ten youth (ages 18-24) were recruited to participate in this study. Participants completed the intervention online. Intervention components focused on medication adherence (rating perceived importance and confidence, and goal setting). Retention was 100% for both intervention sessions. All participants (n=10) felt medication adherence was important, but 80% felt confident they could manage their adherence to HIV medications. Ninety percent of participants set the goal of taking their HIV medications exactly as prescribed and reported success achieving this goal at follow-up. Additionally, participants were satisfied with the quality of the sessions and the amount of assistance they received for managing their adherence to HIV medications (90% participants for Session 1; 89% for Session 2). Per exit interview responses, participants felt that the intervention made them think more about their health and was a motivator for them to take better care of their health. In conclusion, the intervention was feasible for YLH enrolled in the study.

  11. Health-related quality of life in different stages of chronic kidney disease and at initiation of dialysis treatment

    Directory of Open Access Journals (Sweden)

    Pagels Agneta A

    2012-06-01

    Full Text Available Abstract Objectives To evaluate health-related quality of life (HRQoL in patients in different stages of chronic kidney disease (CKD up to initiation of dialysis treatment and to explore possible correlating and influencing factors. Methods Cross-sectional design with 535 patients in CKD stages 2–5 and 55 controls assessed for HRQoL through SF-36 together with biomarkers. Results All HRQoL dimensions deteriorated significantly with CKD stages with the lowest scores in CKD 5. The largest differences between the patient groups were seen in ‘physical functioning’, ‘role physical’, ‘general health’ and in physical summary scores (PCS. The smallest disparities were seen in mental health and pain. Patients in CKD stages 2–3 showed significantly decreased HRQoL compared to matched controls, with differences of large magnitude - effect size (ES ≥ .80 - in ‘general health’ and PCS. Patients in CDK 4 demonstrated deteriorated scores with a large magnitude in ‘physical function’, ‘general health’ and PCS compared to the patients in CKD 2–3. Patients in CKD 5 demonstrated deteriorated scores with a medium sized magnitude (ES 0.5 – 0.79 in ‘role emotional’ and mental summary scores compared to the patients in CKD 4. Glomerular filtration rate Conclusions Having CKD implies impaired HRQoL, also in earlier stages of the disease. At the time for dialysis initiation HRQoL is substantially deteriorated. Co-existing conditions, such as inflammation and cardiovascular disease seem to be powerful predictors of impaired HRQoL in patients with CKD. Within routine renal care, strategies to improve function and well-being considering the management of co-existing conditions like inflammation and CVD need to be developed.

  12. Evaluation of improvement of onychomycosis in HIV-infected patients after initiation of combined antiretroviral therapy without antifungal treatment.

    Science.gov (United States)

    Ruíz-López, Patricia; Moreno-Coutiño, Gabriela; Fernández-Martínez, Ramón; Espinoza-Hernández, Jessica; Rodríguez-Zulueta, Patricia; Reyes-Terán, Gustavo

    2015-09-01

    Onychomycosis in HIV-infected patients has a prevalence of 20-44% and is more frequently seen with CD4(+) T cell counts ≤450 cel μl(-1). There are case reports of improvement in onychomycosis after initiation of combined antiretroviral therapy (cART), but there are no prospective studies that prove the existence and frequency of this phenomenon. The aim of this study was to evaluate if HIV-infected patients with onychomycosis who begin cART improve and/or cure without antifungal treatment. We included HIV-infected patients with onychomycosis who had not started cART and nor received antifungal therapy during 6 months prior to the study. We evaluated affected the nails with the Onychomycosis Severity Index (OSI); nail scrapings were collected and direct microscopy with potassium hydroxide (KOH) as well as mycological culture were performed. We repeated these procedures at 3 and 6 months to assess changes. CD4 T cell counts and HIV viral load were obtained. A total of 16 patients were included, with male gender predominance (68.7%); distal and lateral subungual onychomycosis (DLSO) was the most common form (31.3%). Trichophyton rubrum was the most frequently isolated microorganism. OSI decreased 21.5% at 3 months and 40% at 6 months after initiation of antiretrovirals (P = 0.05). We found a non-significant tendency towards improvement with higher CD4(+) T cell counts and with viral loads <100 000 copies ml(-1). This could be due to the increase in CD4(+) T cells, decreased percentage of Treg (CD4(+)CD25(+)) among CD4(+) Tcells and/or a decreased viral load; further studies are necessary to prove these hypothesis.

  13. The "Win-Win" initiative: a global, scientifically based approach to resource sparing treatment for systemic breast cancer therapy

    Directory of Open Access Journals (Sweden)

    Elzawawy Ahmed

    2009-05-01

    Full Text Available Abstract Background Worldwide, breast cancer is the most frequent malignancy among females. Its incidence shows a trend towards an increase in the next decade, particularly in developing countries where less than of 5% of resources for cancer management are available. In most breast cancer cases systemic cancer treatment remains a primary management strategy. With the increasing costs of novel drugs, amidst the growing breast cancer rate, it can be safely assumed that in the next decade, newly developed cancer drugs will become less affordable and therefore will be available to fewer patients in low and middle income countries. In light of this potentially tragic situation, a pressing need emerges for science-based innovative solutions. Methods In this article, we cite examples of recently published researches and case management approaches that have been shown to lower overall treatment costs without compromising patient outcomes. The cited approaches are not presented as wholly inclusive or definitive solutions but are offered as effective examples that we hope will inspire the development of additional evidence-based management approaches that provide both efficient and effective breast cancer treatment Results We propose a "win-win" initiative, borne in the year of 2008 of strategic information sharing through preparatory communications, publications and our conference presentations. In the year 2009, ideas developed through these mechanisms can be refined through focused small pilot meetings with interested stakeholders, including the clinical, patient advocate, and pharmaceutical communities, and as appropriate (as proposed plans emerge, governmental representatives. The objective is to draw a realistic road map for feasible and innovative scientific strategies and collaborative actions that could lead to resource sparing; i.e. cost effective and tailored breast cancer systemic treatment for low and middle income countries. Conclusion The

  14. Cutaneous manifestations of hepatitis C in the era of new antiviral agents

    Institute of Scientific and Technical Information of China (English)

    Simone; Garcovich; Matteo; Garcovich; Rodolfo; Capizzi; Antonio; Gasbarrini; Maria; Assunta; Zocco

    2015-01-01

    The association of chronic hepatitis C virus(HCV) infection with a wide spectrum of cutaneous manifestations has been widely reported in the literature, with varying strength of epidemiological association. Skin diseases which are certainly related with chronic HCV infection due to a strong epidemiological and pathogenetic association are mixed cryoglobulinemia, lichen planus and porphyria cutanea tarda. Chronic pruritus and necrolytic acral erythema are conditions that may share a possible association with HCV infection, while several immune-mediated inflammatory skin conditions, such as psoriasis, chronic urticaria and vitiligo, have been only anecdotally reported in the setting of chronic HCV infection. Traditional interferonbased treatment regimens for HCV infection are associated with substantial toxicity and a high-risk of immune-related adverse events, while the advent of new direct-acting antivirals with sustained virological response and improved tolerability will open the door for all-oral, interferon-free regimens. In the new era of these direct acting antivirals there will be hopefully a renewed interest in extra-hepatic manifestations of HCV infection. The aim of the present paper is to review the main cutaneous HCV-related disorders- mixed cryoglobulinemia, lichen planus, porphyria cutanea tarda and chronic pruritus- and to discuss the potential impact of new antiviral treatments on the course of these extrahepatic manifestations of chronic HCV infection.

  15. Longitudinal liver stiffness assessment in patients with chronic hepatitis C undergoing antiviral therapy.

    Directory of Open Access Journals (Sweden)

    Stella M Martinez

    Full Text Available BACKGROUND/AIMS: Liver stiffness (LS measurement by means of transient elastography (TE is accurate to predict fibrosis stage. The effect of antiviral treatment and virologic response on LS was assessed and compared with untreated patients with chronic hepatitis C (CHC. METHODS: TE was performed at baseline, and at weeks 24, 48, and 72 in 515 patients with CHC. RESULTS: 323 treated (62.7% and 192 untreated patients (37.3% were assessed. LS experienced a significant decline in treated patients and remained stable in untreated patients at the end of study (P<0.0001. The decline was significant for patients with baseline LS ≥ 7.1 kPa (P<0.0001 and P 0.03, for LS ≥ 9.5 and ≥ 7.1 kPa vs lower values, respectively. Sustained virological responders and relapsers had a significant LS improvement whereas a trend was observed in nonresponders (mean percent change -16%, -10% and -2%, for SVR, RR and NR, respectively, P 0.03 for SVR vs NR. In multivariate analysis, high baseline LS (P<0.0001 and ALT levels, antiviral therapy and non-1 genotype were independent predictors of LS improvement. CONCLUSIONS: LS decreases during and after antiviral treatment in patients with CHC. The decrease is significant in sustained responders and relapsers (particularly in those with high baseline LS and suggests an improvement in liver damage.

  16. Longitudinal Liver Stiffness Assessment in Patients with Chronic Hepatitis C Undergoing Antiviral Therapy

    Science.gov (United States)

    Martinez, Stella M.; Foucher, Juliette; Combis, Jean-Marc; Métivier, Sophie; Brunetto, Maurizia; Capron, Dominique; Bourlière, Marc; Bronowicki, Jean-Pierre; Dao, Thong; Maynard-Muet, Marianne; Lucidarme, Damien; Merrouche, Wassil; Forns, Xavier; de Lédinghen, Victor

    2012-01-01

    Background/Aims Liver stiffness (LS) measurement by means of transient elastography (TE) is accurate to predict fibrosis stage. The effect of antiviral treatment and virologic response on LS was assessed and compared with untreated patients with chronic hepatitis C (CHC). Methods TE was performed at baseline, and at weeks 24, 48, and 72 in 515 patients with CHC. Results 323 treated (62.7%) and 192 untreated patients (37.3%) were assessed. LS experienced a significant decline in treated patients and remained stable in untreated patients at the end of study (P<0.0001). The decline was significant for patients with baseline LS ≥ 7.1 kPa (P<0.0001 and P 0.03, for LS ≥9.5 and ≥7.1 kPa vs lower values, respectively). Sustained virological responders and relapsers had a significant LS improvement whereas a trend was observed in nonresponders (mean percent change −16%, −10% and −2%, for SVR, RR and NR, respectively, P 0.03 for SVR vs NR). In multivariate analysis, high baseline LS (P<0.0001) and ALT levels, antiviral therapy and non-1 genotype were independent predictors of LS improvement. Conclusions LS decreases during and after antiviral treatment in patients with CHC. The decrease is significant in sustained responders and relapsers (particularly in those with high baseline LS) and suggests an improvement in liver damage. PMID:23082200

  17. Antiviral therapy for hepatitis C: Has anything changed for pregnant/lactating women?

    Science.gov (United States)

    Spera, Anna Maria; Eldin, Tarek Kamal; Tosone, Grazia; Orlando, Raffaele

    2016-04-28

    Hepatitis C virus (HCV) affects about 3% of the world's population, with the highest prevalence in individuals under 40. The prevalence in pregnant women varies with geographical distribution (highest in developing countries). Prevalence also increases in sub-populations of women at high risk for blood-transmitted infections. HCV infection in pregnancy represents a non-negligible problem. However, most of the past antiviral regimens cannot be routinely offered to pregnant or breastfeeding women because of their side effects. We briefly reviewed the issue of treatment of HCV infection in pregnant/breastfeeding women focusing on the effects of the new direct-acting antivirals on fertility, pregnancy and lactation in animal studies and on the potential risk for humans based on the pharmacokinetic properties of each drug. Currently, all new therapy regimens are contraindicated in this setting because of lack of sufficient safety information and adequate measures of contraception are still routinely recommended for female patients of childbearing potential.

  18. Direct Acting Antivirals in Patients with Chronic Hepatitis C and Down Syndrome

    Directory of Open Access Journals (Sweden)

    Eric R. Yoo

    2016-01-01

    Full Text Available Patients with Down syndrome who received blood transfusions, likely in conjunction with cardiothoracic surgery for congenital heart disease and prior to the implementation of blood-donor screening for hepatitis C virus infection, face a substantial risk of acquiring the infection. In the past, interferon-based therapy for chronic hepatitis C infection in patients with Down syndrome was noted to have lower efficacy and potentially higher risk of adverse effects. Recently, the treatment for chronic hepatitis C has been revolutionized with the introduction of interferon-free direct acting antivirals with favorable safety, tolerability, and efficacy profile. Based on our experiences, the newly approved sofosbuvir-based direct acting antiviral therapy is well tolerated and highly efficacious in this subpopulation of hepatitis C virus infected patients with Down syndrome.

  19. Interferon lambda 4 signals via the IFNλ receptor to regulate antiviral activity against HCV and coronaviruses

    DEFF Research Database (Denmark)

    Hamming, Ole Jensen; Terczynska-Dyla, Ewa; Vieyres, Gabrielle;

    2013-01-01

    The IFNL4 gene is a recently discovered type III interferon, which in a significant fraction of the human population harbours a frameshift mutation abolishing the IFNλ4 ORF. The expression of IFNλ4 is correlated with both poor spontaneous clearance of hepatitis C virus (HCV) and poor response...... to treatment with type I interferon. Here, we show that the IFNL4 gene encodes an active type III interferon, named IFNλ4, which signals through the IFNλR1 and IL-10R2 receptor chains. Recombinant IFNλ4 is antiviral against both HCV and coronaviruses at levels comparable to IFNλ3. However, the secretion....... Together, these findings result in the paradox that IFNλ4 is strongly antiviral but a disadvantage during HCV infection...

  20. Computer-aided identification, design and synthesis of a novel series of compounds with selective antiviral activity against chikungunya virus.

    Science.gov (United States)

    Bassetto, Marcella; De Burghgraeve, Tine; Delang, Leen; Massarotti, Alberto; Coluccia, Antonio; Zonta, Nicola; Gatti, Valerio; Colombano, Giampiero; Sorba, Giovanni; Silvestri, Romano; Tron, Gian Cesare; Neyts, Johan; Leyssen, Pieter; Brancale, Andrea

    2013-04-01

    Chikungunya virus (CHIKV) is an Arbovirus that is transmitted to humans primarily by the mosquito species Aedes aegypti. Infection with this pathogen is often associated with fever, rash and arthralgia. Neither a vaccine nor an antiviral drug is available for the prevention or treatment of this disease. Albeit considered a tropical pathogen, adaptation of the virus to the mosquito species Aedes albopictus, which is also very common in temperate zones, has resulted in recent outbreaks in Europe and the US. In the present study, we report on the discovery of a novel series of compounds that inhibit CHIKV replication in the low μM range. In particular, we initially performed a virtual screening simulation of ∼5 million compounds on the CHIKV nsP2, the viral protease, after which we investigated and explored the Structure-Activity Relationships of the hit identified in silico. Overall, a series of 26 compounds, including the original hit, was evaluated in a virus-cell-based CPE reduction assay. The study of such selective inhibitors will contribute to a better understanding of the CHIKV replication cycle and may represents a first step towards the development of a clinical candidate drug for the treatment of this disease.

  1. Convergent Transcription of Interferon-stimulated Genes by TNF-α and IFN-α Augments Antiviral Activity against HCV and HEV

    Science.gov (United States)

    Wang, Wenshi; Xu, Lei; Brandsma, Johannes H.; Wang, Yijin; Hakim, Mohamad S.; Zhou, Xinying; Yin, Yuebang; Fuhler, Gwenny M.; van der Laan, Luc J. W.; van der Woude, C. Janneke; Sprengers, Dave; Metselaar, Herold J.; Smits, Ron; Poot, Raymond A.; Peppelenbosch, Maikel P.; Pan, Qiuwei

    2016-01-01

    IFN-α has been used for decades to treat chronic hepatitis B and C, and as an off-label treatment for some cases of hepatitis E virus (HEV) infection. TNF-α is another important cytokine involved in inflammatory disease, which can interact with interferon signaling. Because interferon-stimulated genes (ISGs) are the ultimate antiviral effectors of the interferon signaling, this study aimed to understand the regulation of ISG transcription and the antiviral activity by IFN-α and TNF-α. In this study, treatment of TNF-α inhibited replication of HCV by 71 ± 2.4% and HEV by 41 ± 4.9%. Interestingly, TNF-α induced the expression of a panel of antiviral ISGs (2-11 fold). Blocking the TNF-α signaling by Humira abrogated ISG induction and its antiviral activity. Chip-seq data analysis and mutagenesis assay further revealed that the NF-κB protein complex, a key downstream element of TNF-α signaling, directly binds to the ISRE motif in the ISG promoters and thereby drives their transcription. This process is independent of interferons and JAK-STAT cascade. Importantly, when combined with IFN-α, TNF-α works cooperatively on ISG induction, explaining their additive antiviral effects. Thus, our study reveals a novel mechanism of convergent transcription of ISGs by TNF-α and IFN-α, which augments their antiviral activity against HCV and HEV. PMID:27150018

  2. The Effect of Combination Antiviral Therapy in the Treatment of Hepatitis C on the Occurrence of Depressive Disorder in Patients Treated for Hepatitis C in the Republic of Srpska

    Science.gov (United States)

    Banjac, Visnja; Zivlak-Radulovic, Nera; Miskovic, Mirjana

    2016-01-01

    Background: The current standard treatment of chronic hepatitis C in Bosnia and Herzegovina consists of pegylated interferon alpha in combination with ribavirin. Interferon therapy has many psychiatric side effects, with depressive symptomatology being most prominent. The aim of the study was to establish the frequency and severity of depression in patients with chronic hepatitis C during two months of the aforementioned therapy. Subjects and Methods: The overall sample consisted of 46 subjects, divided into three subgroups, aged 18 to 65. The study population consisted of subjects treated for chronic hepatitis C (n = 15), subjects infected but not treated for chronic hepatitis C (n = 15), and healthy controls (n = 16). The assessment and level of depression were based on the Structural clinical interview (SCID), Montgomery-Asberg Depression Rating Scale and Zung Self-Rating Depression Scale. The assessments were conducted before interferon therapy (on the day 0), after 4 and 8 weeks of therapy. Results: Regarding its frequency, MADRS scoring showed that the number of depressed subjects receiving therapy increased after 8 weeks (46.7%). There was statistical significance between the subgroups after 4 and 8 weeks. Likewise, the ZUNG scale showed that the number of depressed subjects receiving therapy increased after 8 weeks (73.3%). There was statistical significance between the subgroups on the day 0, after 4 and 8 weeks. Conclusions: Depression was significantly more frequent in chronic hepatitis C subjects treated with interferon alpha in combination with ribavirin than in subjects in the group without therapy. Mild depression was most prevalent. PMID:27147788

  3. Behavior of soluble HLA-A, -B, -C and HLA-G molecules in patients with chronic hepatitis C virus infection undergoing pegylated interferon-α and ribavirin treatment: potential role as markers of response to antiviral therapy.

    Science.gov (United States)

    Murdaca, Giuseppe; Contini, Paola; Cagnati, Paola; Marenco, Simona; Pieri, Giulia; Lantieri, Francesca; Picciotto, Antonino; Puppo, Francesco

    2017-02-01

    The serum levels of soluble HLA class I antigens (sHLA-A, -B, -C and sHLA-G) were determined in 40 HCV genotype 1-infected patients before (T 0), after 3, 6, and 12 months (T 3, T 6, and T 12) of pegylated-IFN-α plus ribavirin therapy and 6 months (T 18) after the end of treatment. Twenty patients were sustained virological responders (SVR), and 20 were non-responders (NR). sHLA-A, -B, -C levels at T 0 were significantly higher in both SVR (mean 10.48 μg/ml) and NR (mean 11.87 μg/ml) patients as compared to healthy controls (mean 0.34 μg/ml, p G levels at T 0 were significantly higher in SVR (mean 24.78 ng/ml) and NR (mean 24.93 ng/ml) patients as compared to healthy controls (mean 10.34 ng/ml, p = 0.015 and p = 0.014, respectively) but were lower as compared to HIV-infected subjects (mean 48.00 ng/ml, p G significantly decreased in SVR from T 0 to T 18 (mean 1.64 and 1.43 ng/ml, respectively, p < 0.0001) and correlated with HCV-RNA, AST, ALT, γGT, and ALP levels. The determination of soluble HLA class I levels could be proposed as a surrogate marker to discriminate SVR and NR HCV-infected patients during PEG-IFN-α plus ribavirin therapy.

  4. An antiviral protein from Bougainvillea spectabilis roots; purification and characterisation.

    Science.gov (United States)

    Balasaraswathi, R; Sadasivam, S; Ward, M; Walker, J M

    1998-04-01

    An antiviral protein active against mechanical transmission of tomato spotted wilt virus was identified in the root tissues of Bougainvillea spectabilis Willd. Bougainvillea Antiviral Protein I (BAP I) was purified to apparent homogeneity from the roots of Bougainvillea by ammonium sulphate precipitation, CM- and DEAE-Sepharose chromatography and reverse phase HPLC. BAP I is a highly basic protein (pI value > 8.6) with an Mr of 28,000. The N-terminal sequence of BAP I showed homology with other plant antiviral proteins. Preliminary tests suggest that purified BAP I is capable of interfering with in vitro protein synthesis.

  5. The effect of infliximab on antiviral antibody profiles in patients with rheumatoid arthritis.

    Science.gov (United States)

    Kaufman, Ilana; Moscovici, Yolanda Braun; Abudi, Yair; Sofer, Denit; Mendelson, Ella; Balbir-Gurman, Alexandra; Caspi, Dan; Elkayam, Ori

    2010-01-01

    The duration of humoral immunity in patients treated with immunosuppressive drugs is poorly defined. The objective of the study was to investigate the effect of infliximab on the levels of antiviral antibodies against poliomyelitis, rubella and measles in rheumatoid arthritis (RA) patients. Fifty-two consecutive RA patients being treated with 3 mg/kg infliximab were prospectively studied. The antiviral antibody profiles for measles, rubella and three serotypes of poliomyelitis were tested on the day of the first infusion of infliximab and 6 months later. The study group comprised 36 women and 16 men (mean age 54 years, range 33-81) with a mean disease duration of 15 +/- 9 years. Forty-two (81%) patients were being treated with methotrexate and 22 (42%) were receiving prednisone. All patients had baseline protective levels of antibodies against measles and the three strains of polio, while 48 (92%) patients had protective antibodies against rubella. No significant change in the levels of antiviral antibodies was observed after 6 months of treatment with infliximab: from 3.67 at baseline to 3.87 IU/ml for measles, 169.50-197.0 IU/ml for rubella. No change was noticed for the geometric mean concentrations of antibodies against strains of poliomyelitis: 366-478 IU/ml for the Mahoney polio strain, 906-845 IU/ml for the MEF strain and 175-196 IU/ml for the Sauket strain. Patients with longstanding RA conserve long-term immunity to common viruses despite the use of immunosuppressive drugs. Levels of antiviral antibodies against measles, rubella and polio remain stable under treatment with infliximab.

  6. Bio-mathematical models of viral dynamics to tailor antiviral therapy in chronic viral hepatitis

    Science.gov (United States)

    Brunetto, Maurizia Rossana; Colombatto, Piero; Bonino, Ferruccio

    2009-01-01

    The simulation of the dynamics of viral infections by mathematical equations has been applied successfully to the study of viral infections during antiviral therapy. Standard models applied to viral hepatitis describe the viral load decline in the first 2-4 wk of antiviral therapy, but do not adequately simulate the dynamics of viral infection for the following period. The hypothesis of a constant clearance rate of the infected cells provides an unrealistic estimation of the time necessary to reach the control or the clearance of hepatitis B virus (HBV)/hepatitis C virus (HCV) infection. To overcome the problem, we have developed a new multiphasic model in which the immune system activity is modulated by a negative feedback caused by the infected cells reduction, and alanine aminotransferase kinetics serve as a surrogate marker of infected-cell clearance. By this approach, we can compute the dynamics of infected cells during the whole treatment course, and find a good correlation between the number of infected cells at the end of therapy and the long-term virological response in patients with chronic hepatitis C. The new model successfully describes the HBV infection dynamics far beyond the third month of antiviral therapy under the assumption that the sum of infected and non-infected cells remains roughly constant during therapy, and both target and infected cells concur in the hepatocyte turnover. In clinical practice, these new models will allow the development of simulators of treatment response that will be used as an “automatic pilot” for tailoring antiviral therapy in chronic hepatitis B as well as chronic hepatitis C patients. PMID:19195054

  7. Bio-mathematical models of viral dynamics to tailor antiviral therapy in chronic viral hepatitis

    Institute of Scientific and Technical Information of China (English)

    Maurizia Rossana Brunetto; Piero Colombatto; Ferruccio Bonino

    2009-01-01

    The simulation of the dynamics of viral infections by mathematical equations has been applied successfully to the study of viral infections during antiviral therapy. Standard models applied to viral hepatitis describe the viral load decline in the first 2-4 wk of antiviral therapy, but do not adequately simulate the dynamics of viral infection for the following period. The hypothesis of a constant clearance rate of the infected cells provides an unrealistic estimation of the time necessary to reach the control or the clearance of hepatitis B virus (HBV)/ hepatitis C virus (HCV) infection. To overcome the problem, we have developed a new multiphasic model in which the immune system activity is modulated by a negative feedback caused by the infected cells reduction, and alanine aminotransferase kinetics serve as a surrogate marker of infected-cell clearance. By this approach, we can compute the dynamics of infected cells during the whole treatment course, and find a good correlation between the number of infected cells at the end of therapy and the long-term virological response in patients with chronic hepatitis C. The new model successfully describes the HBV infection dynamics far beyond the third month of antiviral therapy under the assumption that the sum of infected and non-infected cells remains roughly constant during therapy, and both target and infected cells concur in the hepatocyte turnover. In clinical practice, these new models will allow the development of simulators of treatment response that will be used as an "automatic pilot" for tailoring antiviral therapy in chronic hepatitis B as well as chronic hepatitis C patients.

  8. Antiviral therapy in hepatitis C virus cirrhotic patients in compensated and decompensated condition

    Institute of Scientific and Technical Information of China (English)

    Angelo Iacobellis; Antonio Ippolito; Angelo Andriulli

    2008-01-01

    The main goals of treating cirrhotic patients with antiviral therapy are to attain sustained viral clearance (SVR), halt disease progression, and prevent re-infection of the liver graft. However, while the medical need is great, the use of interferon and ribavirin might expose these patients to severe treated-related side effects as a large proportion of them have pre-existing hematological cytopenias. We have reviewed potential benefits and risks associated with antiviral drugs in patients with liver cirrhosis, due to hepatitis C virus (HCV) infection. In cases presenting with bridging fibrosis or cirrhosis, current regimens of antiviral therapy have attained a 44%-48% rate of SVR. In cirrhotic patients with portal hypertension, the SVR rate was 22% overall, 12.5% in patients with genotype 1, and 66.7% in those with genotypes 2 and 3 following therapy with low doses of either Peg-IFN alpha-2b and of ribavirin. In patients with decompensated cirrhosis, full dosages of Peg-IFN alpha-2b and of ribavirin produced a SVR rate of 35% overall, 16% in patients with genotype 1 and 4, and 59% in those with genotype 2 and 3. Use of hematological cytokines will either ensure full course of treatment to be accomplished with and prevent development of treatment-associated side effects. Major benefits after HCV eradication were partial recovery of liver metabolic activity, prevention of hepatitis C recurrence after transplantation, and removal of some patients from the waiting list for liver transplant. Several observations highlighted that therapy is inadvisable for individuals with poor hepatic reserve (ChUd-Pugh-Turcotte score ≥ 10). Although SVR rates are low in decompensated cirrhotics due to hepatitis C, these patients have the most to gain as successful antiviral therapy is potentially lifesaving. C 2008 The W.1G Press. All dghts reserved.

  9. Antiprotozoan and Antiviral Activities of Non-Cytotoxic Truncated and Variant Analogues of Mussel Defensin

    Directory of Open Access Journals (Sweden)

    Philippe Roch

    2004-01-01

    Full Text Available We previously reported the crucial role displayed by loop 3 of defensin isolated from the Mediterranean mussel, Mytilus galloprovincialis, in antibacterial and antifungal activities. We now investigated antiprotozoan and antiviral activities of some previously reported fragments B, D, E, P and Q. Two fragments (D and P efficiently killed Trypanosoma brucei (ID50 4–12 μM and Leishmania major (ID50 12–45 μM in a time/dose-dependent manner. Killing of T. brucei started as early as 1 h after initiation of contact with fragment D and reached 55% mortality after 6 h. Killing was temperature dependent and a temperature of 4°C efficiently impaired the ability to kill T. brucei. Fragments bound to the entire external epithelium of T. brucei. Prevention of HIV-1 infestation was obtained only with fragments P and Q at 20 μM. Even if fragment P was active on both targets, the specificity of fragments D and Q suggest that antiprotozoan and antiviral activities are mediated by different mechanisms. Truncated sequences of mussel defensin, including amino acid replacement to maintain 3D structure and increased positive net charge, also possess antiprotozoan and antiviral capabilities. New alternative and/or complementary antibiotics can be derived from the vast reservoir of natural antimicrobial peptides (AMPs contained in marine invertebrates.

  10. Systems-Biology Approaches to Discover Anti-Viral Effectors of the Human Innate Immune Response

    Directory of Open Access Journals (Sweden)

    Andreas F.R. Sommer

    2011-07-01

    Full Text Available Virus infections elicit an immediate innate response involving antiviral factors. The activities of some of these factors are, in turn, blocked by viral countermeasures. The ensuing battle between the host and the viruses is crucial for determining whether the virus establishes a foothold and/or induces adaptive immune responses. A comprehensive systems-level understanding of the repertoire of anti-viral effectors in the context of these immediate virus-host responses would provide significant advantages in devising novel strategies to interfere with the initial establishment of infections. Recent efforts to identify cellular factors in a comprehensive and unbiased manner, using genome-wide siRNA screens and other systems biology “omics” methodologies, have revealed several potential anti-viral effectors for viruses like Human immunodeficiency virus type 1 (HIV-1, Hepatitis C virus (HCV, West Nile virus (WNV, and influenza virus. This review describes the discovery of novel viral restriction factors and discusses how the integration of different methods in systems biology can be used to more comprehensively identify the intimate interactions of viruses and the cellular innate resistance.

  11. A heritable antiviral RNAi response limits Orsay virus infection in Caenorhabditis elegans N2.

    Directory of Open Access Journals (Sweden)

    Mark G Sterken

    Full Text Available Orsay virus (OrV is the first virus known to be able to complete a full infection cycle in the model nematode species Caenorhabditis elegans. OrV is transmitted horizontally and its infection is limited by antiviral RNA interference (RNAi. However, we have no insight into the kinetics of OrV replication in C. elegans. We developed an assay that infects worms in liquid, allowing precise monitoring of the infection. The assay revealed a dual role for the RNAi response in limiting Orsay virus infection in C. elegans. Firstly, it limits the progression of the initial infection at the step of recognition of dsRNA. Secondly, it provides an inherited protection against infection in the offspring. This establishes the heritable RNAi response as anti-viral mechanism during OrV infections in C. elegans. Our results further illustrate that the inheritance of the anti-viral response is important in controlling the infection in the canonical wild type Bristol N2. The OrV replication kinetics were established throughout the worm life-cycle, setting a standard for further quantitative assays with the OrV-C. elegans infection model.

  12. Methicillin-resistant Staphylococcus epidermidis isolation from the vitrectomy specimen four hours after initial treatment with vancomycin and ceftazidime

    Directory of Open Access Journals (Sweden)

    Golnaz Javey

    2010-02-01

    Full Text Available Golnaz Javey1, Stephen G Schwartz2, Andrew A Moshfeghi2, Sanjay Asrani3, Harry W Flynn Jr21Department of Ophthalmology, Cullen Eye Institute, Baylor College of Medicine, Houston, TX, USA; 2Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, FL, USA; 3Department of Ophthalmology, Duke University Medical Center, Durham, NC, USAAbstract: A patient presented with acute-onset, postoperative endophthalmitis and visual acuity of light perception. Because of a time delay in arranging a pars plana vitrectomy (PPV, the patient was treated with a prompt vitreous tap for culture an injection of vancomycin and ceftazidime. Four hours later, the PPV was performed and additional antibiotics were injected. The cultures from both the initial needle tap and the subsequent PPV isolated methicillin-resistant Staphylococcus epidermidis sensitive to vancomycin, but resistant to fourth-generation fluoroquinolones. The patient eventually recovered a visual acuity of 20/80 before developing retinal detachment. This case illustrates the time lag necessary to sterilize the vitreous cavity, and suggests a possible two-step staged treatment strategy for situations in which access to PPV equipment and support staff may be limited.Keywords: endophthalmitis, pars plana vitrectomy, tap and inject

  13. Kind and estimated stocking amount of antidotes for initial treatment for acute poisoning at emergency medical centers in Korea.

    Science.gov (United States)

    Sohn, Chang Hwan; Ryoo, Seung Mok; Lim, Kyoung Soo; Kim, Won; Lim, Hoon; Oh, Bum Jin

    2014-11-01

    Antidotes for toxicological emergencies can be life-saving. However, there is no nationwide estimation of the antidotes stocking amount in Korea. This study tried to estimate the quantities of stocking antidotes at emergency department (ED). An expert panel of clinical toxicologists made a list of 18 emergency antidotes. The quantity was estimated by comparing the antidote utilization frequency in a multicenter epidemiological study and the nation-wide EDs' data of National Emergency Department Information System (NEDIS). In an epidemiological study of 11 nationwide EDs from January 2009 to December 2010, only 92 (1.9%) patients had been administered emergency antidotes except activated charcoal among 4,870 cases of acute adult poisoning patients. Comparing with NEDIS data, about 1,400,000 patients visited the 124 EDs nationwide due to acute poisoning and about 103,348 adult doses of the 18 emergency antidotes may be required considering poisoning severity score. Of these, 13,224 (1.9%) adult doses of emergency antidotes (575 of atropine, 144 of calcium gluconate or other calcium salts, 2,587 of flumazenil, 3,450 of N-acetylcysteine, 5,893 of pralidoxime, 287 of hydroxocobalamin, 144 of sodium nitrite, and 144 of sodium thiosulfate) would be needed for maintaining the present level of initial treatment with emergency antidotes at EDs in Korea.

  14. Amphipathic DNA polymers exhibit antiviral activity against systemic Murine Cytomegalovirus infection

    Directory of Open Access Journals (Sweden)

    Juteau Jean-Marc

    2009-12-01

    Full Text Available Abstract Background Phosphorothioated oligonucleotides (PS-ONs have a sequence-independent, broad spectrum antiviral activity as amphipathic polymers (APs and exhibit potent in vitro antiviral activity against a broad spectrum of herpesviruses: HSV-1, HSV-2, HCMV, VZV, EBV, and HHV-6A/B, and in vivo activity in a murine microbiocide model of genital HSV-2 infection. The activity of these agents against animal cytomegalovirus (CMV infections in vitro and in vivo was therefore investigated. Results In vitro, a 40 mer degenerate AP (REP 9 inhibited both murine CMV (MCMV and guinea pig CMV (GPCMV with an IC50 of 0.045 μM and 0.16 μM, respectively, and a 40 mer poly C AP (REP 9C inhibited MCMV with an IC50 of 0.05 μM. Addition of REP 9 to plaque assays during the first two hours of infection inhibited 78% of plaque formation whereas addition of REP 9 after 10 hours of infection did not significantly reduce the number of plaques, indicating that REP 9 antiviral activity against MCMV occurs at early times after infection. In a murine model of CMV infection, systemic treatment for 5 days significantly reduced virus replication in the spleens and livers of infected mice compared to saline-treated control mice. REP 9 and REP 9C were administered intraperitoneally for 5 consecutive days at 10 mg/kg, starting 2 days prior to MCMV infection. Splenomegaly was observed in infected mice treated with REP 9 but not in control mice or in REP 9 treated, uninfected mice, consistent with mild CpG-like activity. When REP 9C (which lacks CpG motifs was compared to REP 9, it exhibited comparable antiviral activity as REP 9 but was not associated with splenomegaly. This suggests that the direct antiviral activity of APs is the predominant therapeutic mechanism in vivo. Moreover, REP 9C, which is acid stable, was effective when administered orally in combination with known permeation enhancers. Conclusion These studies indicate that APs exhibit potent, well tolerated

  15. Initial Results of Image-Guided Percutaneous Ablation as Second-Line Treatment for Symptomatic Vascular Anomalies

    Energy Technology Data Exchange (ETDEWEB)

    Thompson, Scott M., E-mail: Thompson.scott@mayo.edu [Mayo Clinic, Mayo Graduate School, Mayo Medical School and the Mayo Clinic Medical Scientist Training Program, College of Medicine (United States); Callstrom, Matthew R., E-mail: callstrom.matthew@mayo.edu; McKusick, Michael A., E-mail: mckusick.michael@mayo.edu; Woodrum, David A., E-mail: woodrum.david@mayo.edu [Mayo Clinic, Department of Radiology, College of Medicine (United States)

    2015-10-15

    PurposeThe purpose of this study was to determine the feasibility, safety, and early effectiveness of percutaneous image-guided ablation as second-line treatment for symptomatic soft-tissue vascular anomalies (VA).Materials and MethodsAn IRB-approved retrospective review was undertaken of all patients who underwent percutaneous image-guided ablation as second-line therapy for treatment of symptomatic soft-tissue VA during the period from 1/1/2008 to 5/20/2014. US/CT- or MRI-guided and monitored cryoablation or MRI-guided and monitored laser ablation was performed. Clinical follow-up began at one-month post-ablation.ResultsEight patients with nine torso or lower extremity VA were treated with US/CT (N = 4) or MRI-guided (N = 2) cryoablation or MRI-guided laser ablation (N = 5) for moderate to severe pain (N = 7) or diffuse bleeding secondary to hemangioma–thrombocytopenia syndrome (N = 1). The median maximal diameter was 9.0 cm (6.5–11.1 cm) and 2.5 cm (2.3–5.3 cm) for VA undergoing cryoablation and laser ablation, respectively. Seven VA were ablated in one session, one VA initially treated with MRI-guided cryoablation for severe pain was re-treated with MRI-guided laser ablation due to persistent moderate pain, and one VA was treated in a planned two-stage session due to large VA size. At an average follow-up of 19.8 months (range 2–62 months), 7 of 7 patients with painful VA reported symptomatic pain relief. There was no recurrence of bleeding at five-year post-ablation in the patient with hemangioma–thrombocytopenia syndrome. There were two minor complications and no major complications.ConclusionImage-guided percutaneous ablation is a feasible,