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Sample records for clearance viral load

  1. Human papillomavirus type 16 viral load measurement as a predictor of infection clearance.

    Science.gov (United States)

    Trevisan, Andrea; Schlecht, Nicolas F; Ramanakumar, Agnihotram V; Villa, Luisa L; Franco, Eduardo L

    2013-08-01

    Viral load measurements may predict whether human papillomavirus (HPV) type 16 infections may become persistent and eventually lead to cervical lesions. Today, multiple PCR methods exist to estimate viral load. We tested three protocols to investigate viral load as a predictor of HPV clearance. We measured viral load in 418 HPV16-positive cervical smears from 224 women participating in the Ludwig-McGill Cohort Study by low-stringency PCR (LS-PCR) using consensus L1 primers targeting over 40 known HPV types, and quantitative real-time PCR (qRT-PCR) targeting the HPV16 E6 and L1 genes. HPV16 clearance was determined by MY09/11 and PGMY PCR testing on repeated smears collected over 5 years. Correlation between viral load measurements by qRT-PCR (E6 versus L1) was excellent (Spearman's rank correlation, ρ = 0.88), but decreased for L1 qRT-PCR versus LS-PCR (ρ = 0.61). Viral load by LS-PCR was higher for HPV16 and related types independently of other concurrent HPV infections. Median duration of infection was longer for smears with high copy number by all three PCR protocols (log rank P<0.05). Viral load is inversely related to HPV16 clearance independently of concurrent HPV infections and PCR protocol.

  2. Interleukin-28B polymorphisms are associated with hepatitis C virus clearance and viral load in a HIV-1-infected cohort

    DEFF Research Database (Denmark)

    Clausen, L N; Weis, N; Astvad, K;

    2011-01-01

    ) of the interferon-¿3 coding interleukin (IL)-28B gene to study the relationship between IL28B SNPs and outcome of HCV infection. Among 206 HIV-1-infected Europeans with evidence of HCV infection, 47 (23%) individuals had cleared HCV and 159 (77%) had developed chronic infection. The exonic rs8103142 CT......, the promoter rs12979860 CT and the intronic rs11881222 AG genotypes were associated with a decreased HCV clearance rate with adjusted odds ratios (aOR) of 0.3 (95% CI, 0.1-0.7), 0.4 (95% CI, 0.2-0.8) and 0.4 (95% CI, 0.2-0.8), respectively. The haplotype block TCG CTA was associated with a decreased HCV...... higher median HCV RNA levels than individuals with unfavourable haplotype blocks (P = 0.05). Our findings suggest that IL28B may account for some differences in HCV outcome but that other factors including the viral genotype, host genetics and the host-virus interaction are likely to influence...

  3. Analysis of viral clearance unit operations for monoclonal antibodies.

    Science.gov (United States)

    Miesegaes, George; Lute, Scott; Brorson, Kurt

    2010-06-01

    Demonstration of viral clearance is a critical step in assuring the safety of biotechnology products. We generated a viral clearance database that contains product information, unit operation process parameters, and viral clearance data from monoclonal antibody and antibody-related regulatory submissions to FDA. Here we present a broad overview of the database and resulting analyses. We report that the diversity of model viruses tested expands as products transition to late-phase. We also present averages and ranges of viral clearance results by Protein A and ion exchange chromatography steps, low pH chemical inactivation, and virus filtration, focusing on retro- and parvoviruses. For most unit operations, an average log reduction value (LRV, a measure of clearance power) for retrovirus of >4 log(10) were measured. Cases where clearance data fell outside of the anticipated range (i.e., outliers) were rationally explained. Lastly, a historical analysis did not find evidence of any improvement trend in viral clearance over time. The data collectively suggest that many unit operations in general can reliably clear viruses.

  4. Interleukin-10 determines viral clearance or persistence in vivo

    Science.gov (United States)

    Brooks, David G; Trifilo, Matthew J.; Edelmann, Kurt H.; Teyton, Luc; McGavern, Dorian B; Oldstone, Michael B A

    2008-01-01

    Persistent viral infections are a major health concern. One obstacle inhibiting the clearance of persistent infections is functional inactivation of antiviral T cells. Although such immunosuppression occurs rapidly after infection, the mechanisms that induce the loss of T-cell activity and promote viral persistence are unknown. Herein we document that persistent viral infection in mice results in a significant upregulation of interleukin (IL)-10 by antigen-presenting cells, leading to impaired T-cell responses. Genetic removal of Il10 resulted in the maintenance of robust effector T-cell responses, the rapid elimination of virus and the development of antiviral memory T-cell responses. Therapeutic administration of an antibody that blocks the IL-10 receptor restored T-cell function and eliminated viral infection. Thus, we identify a single molecule that directly induces immunosuppression leading to viral persistence and demonstrate that a therapy to neutralize IL-10 results in T-cell recovery and the prevention of viral persistence. PMID:17041596

  5. Hepatitis viral load correlates to glutathione levels.

    Science.gov (United States)

    1998-01-01

    Several recent scientific articles have found a direct correlation between Glutathione levels and viral activity for hepatitis B and C. When viral load increases, Glutathione decreases. Researchers from Germany report that adding NAC (N-acetyl cysteine) to HBV producing cells lines can reduce hepatitis viral load 50 fold. Glutathione is used by the liver to help break down toxins. Patients who have chronic infection for more than 90 days should ask their physicians to check their Glutathione levels. A test kit is available from ImmunoSciences Labs; contact information is included. An amino acid, L-Glutamine, can be used with Alpha Lipoic Acid and NAC to increase Glutathione levels. Chlorophyll also offers benefits to people with hepatitis and other infections. Instructions on how to use a special retention enema containing chlorophyll, water, and apple cider vinegar are provided.

  6. Non-invasive Imaging of Sendai Virus Infection in Pharmacologically Immunocompromised Mice: NK and T Cells, but not Neutrophils, Promote Viral Clearance after Therapy with Cyclophosphamide and Dexamethasone.

    Science.gov (United States)

    Mostafa, Heba H; Vogel, Peter; Srinivasan, Ashok; Russell, Charles J

    2016-09-01

    In immunocompromised patients, parainfluenza virus (PIV) infections have an increased potential to spread to the lower respiratory tract (LRT), resulting in increased morbidity and mortality. Understanding the immunologic defects that facilitate viral spread to the LRT will help in developing better management protocols. In this study, we immunosuppressed mice with dexamethasone and/or cyclophosphamide then monitored the spread of viral infection into the LRT by using a noninvasive bioluminescence imaging system and a reporter Sendai virus (murine PIV type 1). Our results show that immunosuppression led to delayed viral clearance and increased viral loads in the lungs. After cessation of cyclophosphamide treatment, viral clearance occurred before the generation of Sendai-specific antibody responses and coincided with rebounds in neutrophils, T lymphocytes, and natural killer (NK) cells. Neutrophil suppression using anti-Ly6G antibody had no effect on infection clearance, NK-cell suppression using anti-NK antibody delayed clearance, and T-cell suppression using anti-CD3 antibody resulted in no clearance (chronic infection). Therapeutic use of hematopoietic growth factors G-CSF and GM-CSF had no effect on clearance of infection. In contrast, treatment with Sendai virus-specific polysera or a monoclonal antibody limited viral spread into the lungs and accelerated clearance. Overall, noninvasive bioluminescence was shown to be a useful tool to study respiratory viral progression, revealing roles for NK and T cells, but not neutrophils, in Sendai virus clearance after treatment with dexamethasone and cyclophosphamide. Virus-specific antibodies appear to have therapeutic potential.

  7. Non-invasive Imaging of Sendai Virus Infection in Pharmacologically Immunocompromised Mice: NK and T Cells, but not Neutrophils, Promote Viral Clearance after Therapy with Cyclophosphamide and Dexamethasone

    Science.gov (United States)

    Mostafa, Heba H.; Vogel, Peter; Srinivasan, Ashok; Russell, Charles J.

    2016-01-01

    In immunocompromised patients, parainfluenza virus (PIV) infections have an increased potential to spread to the lower respiratory tract (LRT), resulting in increased morbidity and mortality. Understanding the immunologic defects that facilitate viral spread to the LRT will help in developing better management protocols. In this study, we immunosuppressed mice with dexamethasone and/or cyclophosphamide then monitored the spread of viral infection into the LRT by using a noninvasive bioluminescence imaging system and a reporter Sendai virus (murine PIV type 1). Our results show that immunosuppression led to delayed viral clearance and increased viral loads in the lungs. After cessation of cyclophosphamide treatment, viral clearance occurred before the generation of Sendai-specific antibody responses and coincided with rebounds in neutrophils, T lymphocytes, and natural killer (NK) cells. Neutrophil suppression using anti-Ly6G antibody had no effect on infection clearance, NK-cell suppression using anti-NK antibody delayed clearance, and T-cell suppression using anti-CD3 antibody resulted in no clearance (chronic infection). Therapeutic use of hematopoietic growth factors G-CSF and GM-CSF had no effect on clearance of infection. In contrast, treatment with Sendai virus—specific polysera or a monoclonal antibody limited viral spread into the lungs and accelerated clearance. Overall, noninvasive bioluminescence was shown to be a useful tool to study respiratory viral progression, revealing roles for NK and T cells, but not neutrophils, in Sendai virus clearance after treatment with dexamethasone and cyclophosphamide. Virus-specific antibodies appear to have therapeutic potential. PMID:27589232

  8. Potential Pitfalls in Estimating Viral Load Heritability.

    Science.gov (United States)

    Leventhal, Gabriel E; Bonhoeffer, Sebastian

    2016-09-01

    In HIV patients, the set-point viral load (SPVL) is the most widely used predictor of disease severity. Yet SPVL varies over several orders of magnitude between patients. The heritability of SPVL quantifies how much of the variation in SPVL is due to transmissible viral genetics. There is currently no clear consensus on the value of SPVL heritability, as multiple studies have reported apparently discrepant estimates. Here we illustrate that the discrepancies in estimates are most likely due to differences in the estimation methods, rather than the study populations. Importantly, phylogenetic estimates run the risk of being strongly confounded by unrealistic model assumptions. Care must be taken when interpreting and comparing the different estimates to each other.

  9. Viral clearance by flow-through mode ion exchange columns and membrane adsorbers.

    Science.gov (United States)

    Miesegaes, G R; Lute, S C; Read, E K; Brorson, K A

    2014-01-01

    Anion exchange (AEX) is a common downstream purification operation for biotechnology products manufactured in cell culture such as therapeutic monoclonal antibodies (mAbs) and Fc-fusion proteins. We present a head-to-head comparison of the viral clearance efficiency of AEX adsorbers and column chromatography using the same process fluids and comparable run conditions. We also present overall trends from the CDER viral clearance database. In our comparison of multiple brands of resins and adsorbers, clearance of three model viruses (PPV, X-MuLV, and PR772) was largely comparable, with some exceptions which may reflect run conditions that had not been optimized on a resin/membrane specific basis.

  10. Viral load: Roche applies for marketing approval for ultrasensitive test.

    Science.gov (United States)

    1998-08-07

    Roche Molecular Systems has applied for FDA permission to market a more sensitive viral load test. The Amplicor HIV-1 Monitor UltraSensitive Method tests viral load as low as 50 copies; current tests are only accurate to 400 copies. There is a widespread consensus among physicians that testing below 400 copies would be a valuable treatment tool.

  11. Viral load of patients with hantavirus pulmonary syndrome in Argentina.

    Science.gov (United States)

    Bellomo, Carla María; Pires-Marczeski, Fanny Clara; Padula, Paula Julieta

    2015-11-01

    Hantavirus causes severe illness including pneumonia, which leads to hospitalization and often death. At present, there is no specific treatment available. The hantavirus pathogenesis is not well understood, but most likely both virus-mediated and host-mediated mechanisms, are involved. The aim of this study was to correlate viral load in samples of hantavirus pulmonary syndrome cases and hantavirus infected individuals, with clinical epidemiological parameters and disease outcome. The variables that could potentially be related with viral load were analyzed. The retrospective study included 73 cases or household contacts, with different clinical evolution. Viral load was measured by reverse-transcription and real time polymerase chain reaction. There was no statistically significant association between blood viral RNA levels and severity of disease. However, viral load was inversely correlated with IgG response in a statistically significant manner. The level of viral RNA was significantly higher in patients infected with Andes virus South lineage, and was markedly low in persons infected with Laguna Negra virus. These results suggest that the infecting viral genotype is associated with disease severity, and that high viral load is associated with a low specific IgG response. Sex, age and disease severity were not related with viral load. Further investigations increasing strikingly the number of cases and also limiting the variables to be studied are necessary.

  12. Viral loads of cerebrospinal fluid in infants with enterovirus meningitis.

    Science.gov (United States)

    Kawashima, Hisashi; Ioi, Hiroaki; Ishii, Chiako; Hasegawa, Yuka; Amaha, Masahiro; Kashiwagi, Yasuyo; Takekuma, Kouji; Hoshika, Akinori; Watanabe, Yasuo

    2008-01-01

    For a better understanding of the role of the viral load, free radicals, and cytokines in viral meningitis, we surveyed cerebrospinal fluid (CSF) obtained from patients below 1 year of age who showed positive for enterovirus. In their first examinations interleukin (IL)-6 and free radicals increased whereas pleocytosis was rarely observed. IL-6 decreased within the short period. Viral loads and free radicals increased simultaneously. IL-6 and free radicals of CSF are helpful for diagnosis and treatment of viral meningitis at an early stage.

  13. Strategies for developing design spaces for viral clearance by anion exchange chromatography during monoclonal antibody production.

    Science.gov (United States)

    Strauss, Daniel M; Cano, Tony; Cai, Nick; Delucchi, Heather; Plancarte, Magdalena; Coleman, Daniel; Blank, Gregory S; Chen, Qi; Yang, Bin

    2010-01-01

    The quality-by-design (QbD) regulatory initiative promotes the development of process design spaces describing the multidimensional effects and interactions of process variables on critical quality attributes of therapeutic products. However, because of the complex nature of production processes, strategies must be devised to provide for design space development with reasonable allocation of resources while maintaining highly dependable results. Here, we discuss strategies for the determination of design spaces for viral clearance by anion exchange chromatography (AEX) during purification of monoclonal antibodies. We developed a risk assessment for AEX using a formalized method and applying previous knowledge of the effects of certain variables and the mechanism of action for virus removal by this process. We then use design-of-experiments (DOE) concepts to perform a highly fractionated factorial experiment and show that varying many process parameters simultaneously over wide ranges does not affect the ability of the AEX process to remove endogenous retrovirus-like particles from CHO-cell derived feedstocks. Finally, we performed a full factorial design and observed that a high degree of viral clearance was obtained for three different model viruses when the most significant process parameters were varied over ranges relevant to typical manufacturing processes. These experiments indicate the robust nature of viral clearance by the AEX process as well as the design space where removal of viral impurities and contaminants can be assured. In addition, the concepts and methodology presented here provides a general approach for the development of design spaces to assure that quality of biotherapeutic products is maintained.

  14. Tissue viral load variability in chronic hepatitis C.

    LENUS (Irish Health Repository)

    Fanning, L

    2012-02-03

    OBJECTIVE: Liver biopsy is regarded as the gold standard for assessing disease activity in chronic hepatitis C, but sampling error is a potential limitation. Whether sampling variability applies equally to viral load assessment as it does to histology is uncertain. To examine this, we compared viral load between right- and left-lobe biopsy specimens from patients infected with hepatitis C virus (HCV). METHODS: Bilobe biopsies were taken from 16 patients who were serum positive for HCV RNA by reverse transcription-polymerase chain reaction. Genotype was identified by reverse line probe hybridization. There was an absence of competing risk factors for infectious and other liver diseases in this patient group. Histology and hepatic viral load were assessed blindly. None of the patients had received antiviral therapy at the time of study. RESULTS: Detection of HCV in right and left lobes was concordant with serum positivity in all cases. The viral load between lobes was highly correlated (p = 0.0003, r = 0.79). In contrast, the histological activity indices of inflammation and fibrosis\\/cirrhosis were poorly correlated between lobes (p = 0.038, r = 0.60, and p = 0.098, r = 0.50, respectively). CONCLUSION: Hepatic viral load variability does not suffer from the same degree of heterogeneity of sampling variability as does histology.

  15. Higher Viral Load and Prolonged Viral Shedding Period is Associated with Impaired Th17 Cell Response in Patients with H1N1 Influenza A

    Institute of Scientific and Technical Information of China (English)

    Gui-lin; Yang; Ying-xia; Liu; Mu-tong; Fang; Wei-long; Liu; Xin-chun; Chen; John; Nunnari; Jing-jing; Xie; Ming-feng; Liao; Ming-xia; Zhang; Guo-bao; Li; Pei-ze; Zhang; Yi; Guan; Bo-ping; Zhou

    2012-01-01

    Objective To explore whether age,disease severity,cytokines and lymphocytes in H1N1 influenza A patients correlate with viral load and clearance.Methods Total of 70 mild and 16 severe patients infected with H1N1 influenza A virus were enrolled in this study.Results It was found that the patients under 14 years old and severe patients displayed significantly higher viral loads and prolonged viral shedding periods compared with the patients over 14 years old and mild patients,respectively(P < 0.05).Moreover,the patients under 14 years old and severe patients displayed significantly lower Th17 cell frequency than the patients over 14 years old and mild patients(P < 0.01).The viral shedding period inversely correlated with the frequency of IL-17+IFN-γ-CD4+ T cells.Additionally,the decreased concentration of serum TGF-β correlated with the decreased frequency of IL-17+IFN-γ-CD4+ T cells.Conclusions Both younger and severe patients are associated with higher viral loads and longer viral shedding periods,which may partially be attributed to the impaired Th17 cell response.

  16. Hepatitis C virus genotypes: A plausible association with viral loads

    Directory of Open Access Journals (Sweden)

    Salma Ghulam Nabi

    2013-01-01

    Full Text Available Background and Aim: The basic aim of this study was to find out the association of genotypes with host age, gender and viral load. Material and Methods: The present study was conducted at Social Security Hospital, Pakistan. This study included 320 patients with chronic hepatitis C virus (HCV infection who were referred to the hospital between November 2011 and July 2012. HCV viral detection and genotyping was performed and the association was seen between genotypes and host age, gender and viral load. Results : The analysis revealed the presence of genotypes 1 and 3 with further subtypes 1a, 1b, 3a, 3b and mixed genotypes 1b + 3a, 1b + 3b and 3a + 3b. Viral load quantification was carried out in all 151 HCV ribonucleic acid (RNA positive patients. The genotype 3a was observed in 124 (82.12% patients, 3b was found in 21 (13.91%, 1a was seen in 2 (1.32%, 1b in 1 (0.66%, mixed infection with 1b + 3a in 1 (0.66%, 1b + 3b in 1 (0.66% and 3a + 3b was also found in 1 (0.66% patient. Viral load quantification was carried out in all 151 HCV RNA positive patients and was compared between the various genotypes. The mean viral load in patients infected with genotype 1a was 2.75 × 10 6 , 1b 3.9 × 10 6 , 3a 2.65 × 10 6 , 3b 2.51 × 10 6 , 1b + 3a 3.4 × 106, 1b + 3b 2.7 × 106 and 3a + 3b 3.5 × 10 6 . An association between different types of genotypes and viral load was observed. Conclusion : Further studies should be carried out to determine the association of viral load with different genotypes so that sufficient data is available and can be used to determine the type and duration of therapy needed and predict disease outcome.

  17. Detection of Viral RNA in Tissues following Plasma Clearance from an Ebola Virus Infected Patient

    Science.gov (United States)

    Bordi, Licia; Castilletti, Concetta; Colavita, Francesca; Quartu, Serena; Nicastri, Emanuele; Lauria, Francesco Nicola; Petrosillo, Nicola; Lanini, Simone; Kobinger, Gary; Zumla, Alimuddin; Di Caro, Antonino; Ippolito, Giuseppe; Capobianchi, Maria Rosaria; Lalle, Eleonora

    2017-01-01

    An unprecedented Ebola virus (EBOV) epidemic occurred in 2013–2016 in West Africa. Over this time the epidemic exponentially grew and moved to Europe and North America, with several imported cases and many Health Care Workers (HCW) infected. Better understanding of EBOV infection patterns in different body compartments is mandatory to develop new countermeasures, as well as to fully comprehend the pathways of human-to-human transmission. We have longitudinally explored the persistence of EBOV-specific negative sense genomic RNA (neg-RNA) and the presence of positive sense RNA (pos-RNA), including both replication intermediate (antigenomic-RNA) and messenger RNA (mRNA) molecules, in the upper and lower respiratory tract, as compared to plasma, in a HCW infected with EBOV in Sierra Leone, who was hospitalized in the high isolation facility of the National Institute for Infectious Diseases “Lazzaro Spallanzani” (INMI), Rome, Italy. We observed persistence of pos-RNA and neg-RNAs in longitudinally collected specimens of the lower respiratory tract, even after viral clearance from plasma, suggesting possible local replication. The purpose of the present study is to enhance the knowledge on the biological features of EBOV that can contribute to the human-to-human transmissibility and to develop effective intervention strategies. However, further investigation is needed in order to better understand the clinical meaning of viral replication and shedding in the respiratory tract. PMID:28056096

  18. Quantitation of viral load using real-time amplification techniques

    NARCIS (Netherlands)

    Niesters, H G

    2001-01-01

    Real-time PCR amplification techniques are currently used to determine the viral load in clinical samples for an increasing number of targets. Real-time PCR reduces the time necessary to generate results after amplification. In-house developed PCR and nucleic acid sequence-based amplification (NASBA

  19. Decreased insulin clearance in individuals with elevated 1-h post-load plasma glucose levels.

    Directory of Open Access Journals (Sweden)

    Maria Adelaide Marini

    Full Text Available Reduced insulin clearance has been shown to predict the development of type 2 diabetes. Recently, it has been suggested that plasma glucose concentrations ≥ 8.6 mmol/l (155 mg/dl at 1 h during an oral glucose tolerance test (OGTT can identify individuals at high risk for type 2 diabetes among those who have normal glucose tolerance (NGT 1 h-high. The aim of this study was to examine whether NGT 1 h-high have a decrease in insulin clearance, as compared with NGT individuals with 1-h post-load glucose <8.6 mmol/l (l (155 mg/dl, NGT 1 h-low. To this end, 438 non-diabetic White individuals were subjected to OGTT and euglycemic-hyperinsulinemic clamp to evaluate insulin clearance and insulin sensitivity. As compared with NGT 1 h-low individuals, NGT 1 h-high had significantly higher 1-h and 2-h post-load plasma glucose and 2-h insulin levels as well as higher fasting glucose and insulin levels. NGT 1 h-high exhibited also a significant decrease in both insulin sensitivity (P<0.0001 and insulin clearance (P = 0.006 after adjusting for age, gender, adiposity measures, and insulin sensitivity. The differences in insulin clearance remained significant after adjustment for fasting glucose (P = 0.02 in addition to gender, age, and BMI. In univariate analyses adjusted for gender and age, insulin clearance was inversely correlated with body weight, body mass index, waist, fat mass, 1-h and 2-h post-load glucose levels, fasting, 1-h and 2-h post-load insulin levels, and insulin-stimulated glucose disposal. In conclusion, our data show that NGT 1 h-high have a reduction in insulin clearance as compared with NGT 1 h-low individuals; this suggests that impaired insulin clearance may contribute to sustained fasting and post-meal hyperinsulinemia.

  20. PEG-Interferon-α ribavirin-induced HCV viral clearance: a pharmacogenetic multicenter Spanish study

    Directory of Open Access Journals (Sweden)

    Javier Milara

    2015-01-01

    Full Text Available Objective: Dual PEGylated interferon-(PEG-IFN and ribavirin therapy has been the main hepatitis C virus (HCV treatment of the last decade. Current direct-acting antiviral agents have improved the outcome of therapy but also have increased the cost and management complexity of treatment. The current study analyzes host genetics, viral and clinical predictors of sustained viral response (SVR to dual PEG-IFN and ribavirin therapy in a representative Spanish population. Methods: Observational prospective multicentre pharmacogenetic cohort study conducted in 12 different hospitals of 12 different Spanish regions. A total of 98 patients with SVR and 106 with non-SVR in response to PEG-IFN and ribavirin therapy were included. 33 single nucleotide polymorphisms located in 24 different genes related with inflammatory, immune and virus response were selected. Clinical and viral data were also analyzed as candidate of SVR predictors. Results: IL-28B (rs12979860, rs7248668, rs8105790, rs8099917 and TNFRSF1B (rs1061622 genotypes, as well as TNFRSF1B/IL-10/TNF(-308 non-TTG and TNFRSF1B/IL- 10/IL-4 non-TTC haplotypes together with lower age, lower basal HCV RNA load, higher basal serum LDL cholesterol values, VHC genotypes 2 and 3 and basal low grade fibrosis 0-2 were associated with a SVR in the univariate analysis. Independent predictors of SVR in the multivariate analysis were IL-28B rs12979860 CC, TNFRSF1B/IL-10/IL-4 non-TTC along with low baseline HCV RNA load and HCV genotypes 2 and 3. Conclusions: IL-28B rs12979860 CC, TNFRSF1B/ IL-10/ IL-4 non-TTC haplotype, low baseline HCV RNA load and HCV genotypes 2 and 3 may help to predict successful outcome to PEG-IFN/ribavirin therapy in Spanish population

  1. Measles viral load may reflect SSPE disease progression

    Directory of Open Access Journals (Sweden)

    Jin L

    2006-06-01

    Full Text Available Abstract Subacute sclerosing panencephalitis (SSPE is a rare, slowly progressive neurological disorder caused by the persistent infection with measles virus (MV. Despite much research into SSPE, its pathology remains obscure. We examined autopsy tissues of eight SSPE patients by real time quantitative PCR, immunohistochemistry and immunoblotting to determine viral load. MV N, M and H gene RNA could be detected in the central nervous system (CNS of all patients and in two non-CNS tissues of one patient. The viral burden between patients differed up to four-fold by quantitative PCR and corresponded with detection of MV protein. The level of both viral RNA and antigen in the brain may correlate with disease progression.

  2. Intra-operative colloid administration increases the clearance of a post-operative fluid load

    DEFF Research Database (Denmark)

    Borup, Tine; Hahn, Robert; Holte, K;

    2009-01-01

    BACKGROUND: It is unknown whether an intra-operative colloid infusion alters the dynamics of a crystalloid load administered post-operatively. METHODS: Ten patients received 12.5 ml/kg of Ringer's lactate over 30 min 1-3 days before and 4 h after laparoscopic cholecystectomy, during which 10 ml....../kg of a colloid solution, hydroxyethylstarch (HES 130/0.4), was infused. The total body clearance of the pre- and post-operative test infusions was taken as the ratio between the urinary excretion and the Hb-derived dilution of venous plasma over 150 min. The plasma clearance of the infused fluid was calculated...... using volume kinetics based on the plasma dilution alone. The pre-operative plasma clearance was compared with the post-operative plasma clearance and patients served as their own control. RESULTS: The urinary excretion averaged 350 ml for the pre-operative infusion and 612 ml post-operatively, which...

  3. Genomic Loads and Genotypes of Respiratory Syncytial Virus: Viral Factors during Lower Respiratory Tract Infection in Chilean Hospitalized Infants

    Science.gov (United States)

    Espinosa, Yazmín; San Martín, Camila; Torres, Alejandro A.; Farfán, Mauricio J.; Torres, Juan P.; Avadhanula, Vasanthi; Piedra, Pedro A.; Tapia, Lorena I.

    2017-01-01

    The clinical impact of viral factors (types and viral loads) during respiratory syncytial virus (RSV) infection is still controversial, especially regarding newly described genotypes. In this study, infants with RSV bronchiolitis were recruited to describe the association of these viral factors with severity of infection. RSV antigenic types, genotypes, and viral loads were determined from hospitalized patients at Hospital Roberto del Río, Santiago, Chile. Cases were characterized by demographic and clinical information, including days of lower respiratory symptoms and severity. A total of 86 patients were included: 49 moderate and 37 severe cases. During 2013, RSV-A was dominant (86%). RSV-B predominated in 2014 (92%). Phylogenetic analyses revealed circulation of GA2, Buenos Aires (BA), and Ontario (ON) genotypes. No association was observed between severity of infection and RSV group (p = 0.69) or genotype (p = 0.87). After a clinical categorization of duration of illness, higher RSV genomic loads were detected in infants evaluated earlier in their disease (p < 0.001) and also in infants evaluated later, but coursing a more severe infection (p = 0.04). Although types and genotypes did not associate with severity in our children, higher RSV genomic loads and delayed viral clearance in severe patients define a group that might benefit from new antiviral therapies. PMID:28335547

  4. Measurement of contact angle in a clearance-fit pin-loaded hole

    Science.gov (United States)

    Prabhakaran, R.; Naik, R. A.

    1986-01-01

    A technique which measures load-contact variation in a clearance-fit, pin-loaded hole is presented in detail. A steel instrumented pin, which activates a make-or-break electrical circuit in the pin-hole contact region, was inserted into one aluminum and one polycarbonate specimen. The resulting load-contact variations are indicated schematically. The ability to accurately determine the arc of contact at any load was crucial to this measurement. It is noted that this simple experimental technique is applicable to both conducting and nonconducting materials.

  5. Impact of Chloroquine on Viral Load in Breast Milk

    Science.gov (United States)

    Semrau, Katherine; Kuhn, Louise; Kasonde, Prisca; Sinkala, Moses; Kankasa, Chipepo; Shutes, Erin; Vwalika, Cheswa; Ghosh, Mrinal; Aldrovandi, Grace; Thea, Donald M.

    2006-01-01

    Summary The anti-malarial agent chloroquine has activity against HIV. We compared the effect of chloroquine (n = 18) to an anti-malarial agent without known anti-HIV-activity, sulfadoxine-pyrimethamine (n = 12), on breast milk HIV RNA levels among HIV-infected breastfeeding women in Zambia. After adjusting for CD4 count and plasma viral load, chloroquine was associated with a trend towards lower levels of HIV RNA in breast milk compared with sulfadoxine-pyrimethamine (P 0.05). Higher breastmilk viral load was also observed among women receiving presumptive treatment = for symptomatic malaria compared with asymptomatic controls and among controls reporting fever in the prior week. Further research is needed to determine the potential role of chloroquine in prevention of HIV transmission through breastfeeding. Impacte de la chloroquine sur la charge virale dans le lait maternelle La chloroquine, agent antimalarique, a une activité contre le VIH. Nous avons comparé l’effet de la chloroquine à celui d’un autre agent antimalarique, la sulfadoxine-pyrimethamine, dont l’activité sur le VIH n’est pas connue, en mesurant les taux d’ARN de VIH dans le lait maternel de femmes allaitantes infectées par le VIH en Zambie. Après ajustement pour les taux de CD4 et la charge virale dans le plasma, la chloroquine comparée à la sulfadoxine pyrimethamine était associée à une tendance vers des teneurs plus bas en ARN de VIH dans le lait maternel (P = 0,05). Des charges virales plus élevées dans le lait maternel étaient aussi observées chez des femmes recevant un traitement présomptif pour des symptômes de malaria par rapport aux contrôles asymptomatiques et par rapport à des contrôles rapportant de la fièvre durant la première semaine. Des études supplémentaires sont nécessaires pour déterminer le rôle potentiel de la chloroquine dans la prévention de la transmission du VIH par l’allaitement maternel. mots clésVIH, malaria, allaitement maternel

  6. Diagnosing norovirus-associated infectious intestinal disease using viral load

    Directory of Open Access Journals (Sweden)

    Tam Clarence C

    2009-05-01

    Full Text Available Abstract Background Reverse transcription-polymerase chain reaction (RT-PCR is the main method for laboratory diagnosis of norovirus-associated infectious intestinal disease (IID. However, up to 16% of healthy individuals in the community, with no recent history of IID, may be RT-PCR positive; so it is unclear whether norovirus is actually the cause of illness in an IID case when they are RT-PCR positive. It is important to identify the pathogen causing illness in sporadic IID cases, for clinical management and for community based incidence studies. The aim of this study was to investigate how faecal viral load can be used to determine when norovirus is the most likely cause of illness in an IID case. Methods Real-time RT-PCR was used to determine the viral load in faecal specimens collected from 589 IID cases and 159 healthy controls, who were infected with genogroup II noroviruses. Cycle threshold (Ct values from the real-time RT-PCR were used as a proxy measure of viral load. Receiver-operating characteristic (ROC analysis was used to identify a cut-off in viral load for attributing illness to norovirus in IID cases. Results One hundred and sixty-nine IID cases and 159 controls met the inclusion criteria for the ROC analysis. The optimal Ct value cut-off for attributing IID to norovirus was 31. The same cut-off was selected when using healthy controls, or IID cases who were positive by culture for bacterial pathogens, as the reference negative group. This alternative reference negative group can be identified amongst specimens routinely received in clinical virology laboratories. Conclusion We demonstrated that ROC analysis can be used to select a cut-off for a norovirus real time RT-PCR assay, to aid clinical interpretation and diagnose when norovirus is the cause of IID. Specimens routinely received for diagnosis in clinical virology laboratories can be used to select an appropriate cut-off. Individual laboratories can use this method to

  7. High heritability is compatible with the broad distribution of set point viral load in HIV carriers.

    Directory of Open Access Journals (Sweden)

    Sebastian Bonhoeffer

    2015-02-01

    Full Text Available Set point viral load in HIV patients ranges over several orders of magnitude and is a key determinant of disease progression in HIV. A number of recent studies have reported high heritability of set point viral load implying that viral genetic factors contribute substantially to the overall variation in viral load. The high heritability is surprising given the diversity of host factors associated with controlling viral infection. Here we develop an analytical model that describes the temporal changes of the distribution of set point viral load as a function of heritability. This model shows that high heritability is the most parsimonious explanation for the observed variance of set point viral load. Our results thus not only reinforce the credibility of previous estimates of heritability but also shed new light onto mechanisms of viral pathogenesis.

  8. Dynamic load sharing behavior of transverse-torsional coupled planetary gear train with multiple clearances

    Institute of Scientific and Technical Information of China (English)

    盛冬平; 朱如鹏; 靳广虎; 陆凤霞; 鲍和云

    2015-01-01

    A new nonlinear transverse-torsional coupled model with backlash and bearing clearance was proposed for planetary gear set. Meanwhile, sun gear and planet’s eccentricity errors, static transmission error, and time-varying meshing stiffness were taken into consideration. The differential governing equations of motion were solved by employing variable step-size Rung-Kutta numerical integration method. The behavior of dynamic load sharing characteristics affected by the system parameters including input rate, sun gear’s supporting stiffness and eccentricity error, planet’s eccentricity error, sun gear’s bearing clearance, backlashes of sun-planet and planet-ring meshes were investigated qualitatively and systematically. Some theoretical results are summarized at last which extend the current understanding of the dynamic load sharing behavior of planet gear train, enrich the related literature and provide references for the design of planetary gear train.

  9. MBL2 Genetic Variants in HCV Infection Susceptibility, Spontaneous Viral Clearance and Pegylated Interferon Plus Ribavirin Treatment Response.

    Science.gov (United States)

    Zupin, L; Polesello, V; Alberi, G; Moratelli, G; Crocè, S L; Masutti, F; Pozzato, G; Crovella, S; Segat, L

    2016-07-01

    Hepatitis C is disease that damages the liver, and it is caused by the hepatitis C virus (HCV). The pathology became chronic in about 80% of the cases due to virus persistence in the host organism. The standard of care consists of pegylated interferon plus ribavirin; however, the treatment response is very variable and different host/viral factors may concur in the disease outcome. The mannose-binding protein C (MBL) is a component of the innate immune system, able to recognize HCV and consecutively activating the immune response. MBL is encoded by MBL2 gene, and polymorphisms, two in the promoter region (H/L and X/Y) and three in exon 1 (at codon 52, 54 and 57), have been described as functionally influencing protein expression. In this work, 203 Italian HCV patients and 61 healthy controls were enrolled and genotyped for the five MBL2 polymorphisms mentioned above to investigate their role in HCV infection susceptibility, spontaneous viral clearance and treatment response. MBL2 polymorphisms were not associated with HCV infection susceptibility and with spontaneous viral clearance, while MBL2 O allele, O/O genotype, HYO haplotype and DP combined genotype (all correlated with low or deficient MBL expression) were associated with sustained virological response. Moreover, a meta-analysis to assess the role of MBL2 polymorphisms in HCV infection susceptibility was also performed: YA haplotype could be associated with protection towards HCV infection.

  10. An HIV epidemic model based on viral load dynamics: value in assessing empirical trends in HIV virulence and community viral load.

    Science.gov (United States)

    Herbeck, Joshua T; Mittler, John E; Gottlieb, Geoffrey S; Mullins, James I

    2014-06-01

    Trends in HIV virulence have been monitored since the start of the AIDS pandemic, as studying HIV virulence informs our understanding of HIV epidemiology and pathogenesis. Here, we model changes in HIV virulence as a strictly evolutionary process, using set point viral load (SPVL) as a proxy, to make inferences about empirical SPVL trends from longitudinal HIV cohorts. We develop an agent-based epidemic model based on HIV viral load dynamics. The model contains functions for viral load and transmission, SPVL and disease progression, viral load trajectories in multiple stages of infection, and the heritability of SPVL across transmissions. We find that HIV virulence evolves to an intermediate level that balances infectiousness with longer infected lifespans, resulting in an optimal SPVL∼4.75 log10 viral RNA copies/mL. Adaptive viral evolution may explain observed HIV virulence trends: our model produces SPVL trends with magnitudes that are broadly similar to empirical trends. With regard to variation among studies in empirical SPVL trends, results from our model suggest that variation may be explained by the specific epidemic context, e.g. the mean SPVL of the founding lineage or the age of the epidemic; or improvements in HIV screening and diagnosis that results in sampling biases. We also use our model to examine trends in community viral load, a population-level measure of HIV viral load that is thought to reflect a population's overall transmission potential. We find that community viral load evolves in association with SPVL, in the absence of prevention programs such as antiretroviral therapy, and that the mean community viral load is not necessarily a strong predictor of HIV incidence.

  11. An HIV epidemic model based on viral load dynamics: value in assessing empirical trends in HIV virulence and community viral load.

    Directory of Open Access Journals (Sweden)

    Joshua T Herbeck

    2014-06-01

    Full Text Available Trends in HIV virulence have been monitored since the start of the AIDS pandemic, as studying HIV virulence informs our understanding of HIV epidemiology and pathogenesis. Here, we model changes in HIV virulence as a strictly evolutionary process, using set point viral load (SPVL as a proxy, to make inferences about empirical SPVL trends from longitudinal HIV cohorts. We develop an agent-based epidemic model based on HIV viral load dynamics. The model contains functions for viral load and transmission, SPVL and disease progression, viral load trajectories in multiple stages of infection, and the heritability of SPVL across transmissions. We find that HIV virulence evolves to an intermediate level that balances infectiousness with longer infected lifespans, resulting in an optimal SPVL∼4.75 log10 viral RNA copies/mL. Adaptive viral evolution may explain observed HIV virulence trends: our model produces SPVL trends with magnitudes that are broadly similar to empirical trends. With regard to variation among studies in empirical SPVL trends, results from our model suggest that variation may be explained by the specific epidemic context, e.g. the mean SPVL of the founding lineage or the age of the epidemic; or improvements in HIV screening and diagnosis that results in sampling biases. We also use our model to examine trends in community viral load, a population-level measure of HIV viral load that is thought to reflect a population's overall transmission potential. We find that community viral load evolves in association with SPVL, in the absence of prevention programs such as antiretroviral therapy, and that the mean community viral load is not necessarily a strong predictor of HIV incidence.

  12. Viral load of human bocavirus-1 in stools from children with viral diarrhoea in Paraguay.

    Science.gov (United States)

    Proenca-Modena, J L; Martinez, M; Amarilla, A A; Espínola, E E; Galeano, M E; Fariña, N; Russomando, G; Aquino, V H; Parra, G I; Arruda, E

    2013-12-01

    Since their discovery, four species of human bocavirus (HBoV) have been described in patients with respiratory and gastrointestinal diseases. However, a clear causal association between HBoV-1 and gastroenteritis has not been demonstrated. In this study, we describe the detection and quantification of HBoV-1 in stools from children with acute non-bacterial gastroenteritis using quantitative polymerase chain reaction. HBoV-1 genome was detected in 10.6% of stools with frequent association with rotavirus and norovirus. The median of HBoV-1 viral load was 1.88 × 104 genome/ml, lower than previously shown in secretions of patients with respiratory infections, without any obvious association between high viral load and presence of HBoV as single agent. Thus, although HBoV-1 was frequently detected in these patients, there is no clear causal association of this agent with diarrhoea. Indeed, HBoV-1 DNA in stools of patients with gastroenteritis without respiratory symptoms may be a remnant of previous infections or associated with prolonged shedding of virus in the respiratory or digestive tracts.

  13. Soldier-relevant body borne load impacts minimum foot clearance during obstacle negotiation.

    Science.gov (United States)

    Brown, T N; Loverro, K L; Schiffman, J M

    2016-07-01

    Soldiers often trip and fall on duty, resulting in injury. This study examined ten male soldiers' ability to negotiate an obstacle. Participants had lead and trail foot minimum foot clearance (MFC) parameters quantified while crossing a low (305 mm) and high (457 mm) obstacle with (19.4 kg) and without (6 kg) body borne load. To minimize tripping risk, participants increased lead foot MFC (p = 0.028) and reduced lead (p = 0.044) and trail (p = 0.035) foot variability when negotiating an obstacle with body borne load. While obstacle height had no effect on MFC (p = 0.273 and p = 0.126), placing the trail foot closer to the high obstacle when crossing with body borne load, resulted in greater lead (R = 0.640, b = 0.241, p = 0.046) and trail (R = 0.636, b = 0.287, p = 0.048) MFC. Soldiers, when carrying typical military loads, may be able to minimize their risk of tripping over an obstacle by creating a safety margin via greater foot clearance with reduced variability.

  14. Factors influencing a low rate of hepatitis C viral RNA clearance in heroin users from Southern China

    Institute of Scientific and Technical Information of China (English)

    ShengHan Lai; Jin-Bing Zhang; Wei Liu; Jie Chen; Xiao-Fang Yu

    2008-01-01

    AIM: To study the virological and host factors influencing hepatitis C infection outcomes in heroin users in southern China.METHODS: HCV RNA and associated factors were analyzed among 347 heroin users from Guangxi Zhuang Autonomous Region, southern China who were hepatitis C virus (HCV) EIA positive for two or more consecutive visits.RESULTS: Using the COBAS AMPLICOR HCV TEST, a remarkably low HCV RNA negative rate of 8.6% was detected. After multivariate logistic regression analysis, HCV RNA clearance was significantly associated with the presence of HBsAg (OR = 8.436, P < 0.0001), the lack of HIV-1 infection (OR = 0.256, P = 0.038) and age younger than 25 (OR = 0.400, P = 0.029).CONCLUSION: Our study suggests HCV infection among Chinese heroin users results in high levels of viral persistence even amidst factors previously found to enhance viral clearance. Prospective studies of a possible genetic component within the Chinese population and the pathogenicity of non-genotype 1 HCV infections are needed.

  15. The impact of cidofovir treatment on viral loads in adult recurrent respiratory papillomatosis.

    Science.gov (United States)

    Mikolajczak, S; Quante, G; Weissenborn, S; Wafaisade, A; Wieland, U; Lüers, J C; Klussmann, J P; Beutner, D

    2012-12-01

    Cidofovir is an antiviral agent used in the therapy of recurrent respiratory papillomatosis (RRP). In this study, we hypothesized that cidofovir is effective in decreasing the viral load of human papillomavirus (HPV). We established a type specific real-time PCR and measured HPV DNA loads. The course of viral load of HPV types 6 and 11 after repeated applications of cidofovir intralesionally was compared to the clinical outcome using a modified Derkay score. In 6 of the 8 (75 %) patients, we detected HPV 6. In 2 (25 %) patients, we detected HPV 11. In all of the patients, the viral load and the modified Derkay score decreased significantly during the treatment. We conclude that viral load of HPV can be monitored using the technique described here. Cidofovir in combination with surgical debulking reduces the viral load in patients with RRP. Relapses of the symptoms cannot be avoided but might be delayed.

  16. HIV-1 transmitting couples have similar viral load set-points in Rakai, Uganda.

    Directory of Open Access Journals (Sweden)

    T Déirdre Hollingsworth

    2010-05-01

    Full Text Available It has been hypothesized that HIV-1 viral load set-point is a surrogate measure of HIV-1 viral virulence, and that it may be subject to natural selection in the human host population. A key test of this hypothesis is whether viral load set-points are correlated between transmitting individuals and those acquiring infection. We retrospectively identified 112 heterosexual HIV-discordant couples enrolled in a cohort in Rakai, Uganda, in which HIV transmission was suspected and viral load set-point was established. In addition, sequence data was available to establish transmission by genetic linkage for 57 of these couples. Sex, age, viral subtype, index partner, and self-reported genital ulcer disease status (GUD were known. Using ANOVA, we estimated the proportion of variance in viral load set-points which was explained by the similarity within couples (the 'couple effect'. Individuals with suspected intra-couple transmission (97 couples had similar viral load set-points (p = 0.054 single factor model, p = 0.0057 adjusted and the couple effect explained 16% of variance in viral loads (23% adjusted. The analysis was repeated for a subset of 29 couples with strong genetic support for transmission. The couple effect was the major determinant of viral load set-point (p = 0.067 single factor, and p = 0.036 adjusted and the size of the effect was 27% (37% adjusted. Individuals within epidemiologically linked couples with genetic support for transmission had similar viral load set-points. The most parsimonious explanation is that this is due to shared characteristics of the transmitted virus, a finding which sheds light on both the role of viral factors in HIV-1 pathogenesis and on the evolution of the virus.

  17. Combined Effects of Gravity, Bending Moment, Bearing Clearance, and Input Torque on Wind Turbine Planetary Gear Load Sharing: Preprint

    Energy Technology Data Exchange (ETDEWEB)

    Guo, Y.; Keller, J.; LaCava, W.

    2012-09-01

    This computational work investigates planetary gear load sharing of three-mount suspension wind turbine gearboxes. A three dimensional multibody dynamic model is established, including gravity, bending moments, fluctuating mesh stiffness, nonlinear tooth contact, and bearing clearance. A flexible main shaft, planetary carrier, housing, and gear shafts are modeled using reduced degrees-of-freedom through modal compensation. This drivetrain model is validated against the experimental data of Gearbox Reliability Collaborative for gearbox internal loads. Planet load sharing is a combined effect of gravity, bending moment, bearing clearance, and input torque. Influences of each of these parameters and their combined effects on the resulting planet load sharing are investigated. Bending moments and gravity induce fundamental excitations in the rotating carrier frame, which can increase gearbox internal loads and disturb load sharing. Clearance in carrier bearings reduces the bearing load carrying capacity and thus the bending moment from the rotor can be transmitted into gear meshes. With bearing clearance, the bending moment can cause tooth micropitting and can induce planet bearing fatigue, leading to reduced gearbox life. Planet bearings are susceptible to skidding at low input torque.

  18. PEG-Interferon-α ribavirin-induced HCV viral clearance: a pharmacogenetic multicenter Spanish study.

    Science.gov (United States)

    Milara, Javier; Outeda-Macias, Maria; Aumente-Rubio, M Dolores; Más-Serrano, Patricio; Aldaz, Azucena; Calvo, M Victoria; García-Simón, M Sergia; Martin-Barbero, Marisa; Padullés-Zamora, Núria; Schoenenberger, Juan Antonio; Saavedra-Aldrich, Marianne; Tévar-Alfonso, Enrique; Saval, Ana; Pastor-Clerigues, Alfonso; García, Marta; Margusino-Framiñan, Luis; Montero-Alvarez, Jose Luis; Merino, Esperanza; Herrero, Jose Ignacio; Beunza, Mónica; Conesa-Zamora, Pablo; Gimenez-Manzorro, Alvaro; Comas-Sugrañes, Dolors; Cano-Marron, Manuel; Jiménez-Mutiloa, Elena; Díaz-Ruíz, Pilar; Cortijo, Julio

    2015-01-01

    Objetivo: El interferon-pegilado (IFN-PEG) junto a ribavirina ha sido el principal tratamiento de la infeccion por el virus de la hepatitis C (VHC) de la ultima decada. Los agentes antivirales de accion directa actuales han mejorado los resultados de la terapia, pero tambien han aumentado el costo y la gestion de la complejidad del tratamiento. El presente estudio analiza factores geneticos de los pacientes, asi como predictores virales y clinicos de respuesta sostenida viral (RSV) al tratamiento con IFN-PEG y ribavirina en poblacion Espanola. Métodos: Estudio farmacogenetico, multicentrico, prospectivo, observacional de cohortes realizado en 12 hospitales diferentes de 12 comunidades autonomas diferentes. Se incluyeron un total de 98 pacientes con RVS y 106 sin SVR al tratamiento con IFNPEG y ribavirina. Se seleccionaron 33 polimorfismos de nucleotido unico ubicados en 24 genes diferentes relacionados con la respuesta inflamatoria, inmunologica y viral. Los datos clinicos y virales tambien se analizaron como candidatos predictores de RVS. Resultados: Los genotipos IL-28B (rs12979860, rs7248668, rs8105790, rs8099917) y TNFRSF1B (rs1061622), asi como los haplotipos TNFRSF1B / IL-10 / TNF(-308) no-TTG y TNFRSF1B / IL-10 / IL-4 no-TTC junto con la menor edad, menor carga de ARN-VHC basal, valores elevados de colesterol LDL en suero basal, genotipos VHC2 y 3 y bajo grado de fibrosis basal (0-2) se asociaron con una RVS en el analisis univariante. Los predictores independientes de RVS en el analisis multivariante fueron el genotipo IL-28B rs12979860 CC, el haplotipo TNFRSF1B / IL-10 / IL-4 no-TTC junto con los bajos niveles basales de VHCARN y los genotipos virales VHC2 y 3. Conclusiones: El genotipo IL-28B rs12979860 CC, el haplotipo TNFRSF1B / IL-10 / IL-4 haplotipos no-TTC, la carga viral basal baja y los genotipos del VHC2 y 3 pueden ayudar a predecir una buena respuesta a la terapia con IFN-PEG y ribavirina en poblacion espanola.

  19. Edge loading in metal-on-metal hips: low clearance is a new risk factor

    Science.gov (United States)

    Zografos, Angelos; Sayles, Ritchie S; Hart, Alister; Cann, Philippa

    2012-01-01

    The revision rate of large head metal-on-metal and resurfacing hips are significantly higher than conventional total hip replacements. The revision of these components has been linked to high wear caused by edge loading; which occurs when the head–cup contact patch extends over the cup rim. There are two current explanations for this; first, there is loss of entrainment of synovial fluid resulting in breakdown of the lubricating film and second, edge loading results in a large local increase in contact pressure and consequent film thickness reduction at the cup rim, which causes an increase in wear. This paper develops a method to calculate the distance between the joint reaction force vector and the cup rim – the contact patch centre to rim (CPCR) distance. However, the critical distance for the risk of edge loading is the distance from the contact patch edge to rim (CPER) distance. An analysis of explanted hip components, divided into edge worn and non-edge-worn components showed that there was no statistical difference in CPCR values, but the CPER value was significantly lower for edge worn hips. Low clearance hips, which have a more conformal contact, have a larger diameter contact patch and thus are more at risk of edge loading for similarly positioned hips. PMID:22558836

  20. INTERRELATIONS BETWEEN IMMUNOLOGICAL ALTERATIONS AND VIRAL LOAD IN ACUTE HEPATITIS B

    Directory of Open Access Journals (Sweden)

    A. A. Savchenko

    2011-01-01

    Full Text Available Abstract. A group of seventy-six patients with acute viral hepatitis B (HB was under study, in order to evaluate immunological parameters, and ability of blood mononuclear cells to produce cytokines, as dependent on individual viral loads. The immune parameters were less affected in cases of low viral load. Meanwhile, the immune profiles exhibited maximal alterations in the patients with medium and high viral loads. Most expressed changes of immune parameters are found in patients with moderate and high  virus load. Meanwhile, moderate  HB  viral  loads  are  associated  with  higher  functional  activity  of  B-cells  and  lower  NK  numbers, whereas high viral loads correlated with increased amounts of peripheral B cells and higher CD25+ lymphocyte levels. Increased background cytokine synthesis is revealed in mononuclear cells of the patients with acute HB, being, however, suppressed upon additional functional induction. An increased viral load is associated with decreased basal levels of TNFα synthesis. (Med. Immunol., 2011, vol. 13, N 2-3, pp 181-188 

  1. Effects of sex and generation on hepatitis B viral load in families with hepatocellular carcinoma

    Science.gov (United States)

    Hsieh, Ai-Ru; Fann, Cathy SJ; Yeh, Chau-Ting; Lin, Hung-Chun; Wan, Shy-Yi; Chen, Yi-Cheng; Hsu, Chia-Lin; Tai, Jennifer; Lin, Shi-Ming; Tai, Dar-In

    2017-01-01

    AIM To explore factors associated with persistent hepatitis B virus (HBV) infection in a cohort of hepatocellular carcinoma (HCC)-affected families and then investigate factors that correlate with individual viral load among hepatitis B surface antigen (HBsAg)-positive relatives. METHODS We evaluated non-genetic factors associated with HBV replication in relatives of patients with HCC. Relatives of 355 HCC cases were interviewed using a structured questionnaire. Demographics, relationship to index case, HBsAg status of mothers and index cases were evaluated for association with the HBV persistent infection or viral load by generalized estimating equation analysis. RESULTS Among 729 relatives enrolled, parent generation (P = 0.0076), index generation (P = 0.0044), mothers positive for HBsAg (P = 0.0007), and HBsAg-positive index cases (P = 5.98 × 10-8) were associated with persistent HBV infection. Factors associated with HBV viral load were evaluated among 303 HBsAg-positive relatives. Parent generation (P = 0.0359) and sex (P = 0.0007) were independent factors associated with HBV viral load. The intra-family HBV viral load was evaluated in families clustered with HBsAg-positive siblings. An intra-family trend of similar HBV viral load was found for 27 of 46 (58.7%) families. Male offspring of HBsAg-positive mothers (P = 0.024) and older siblings were associated with high viral load. CONCLUSION Sex and generation play important roles on HBV viral load. Maternal birth age and nutritional changes could be the reasons of viral load difference between generations. PMID:28223732

  2. Mapping HIV community viral load: space, power and the government of bodies.

    Science.gov (United States)

    Gagnon, Marilou; Guta, Adrian

    2012-12-01

    HIV plasma viral load testing has become more than just a clinical tool to monitor treatment response at the individual level. Increasingly, individual HIV plasma viral load testing is being reported to public health agencies and is used to inform epidemiological surveillance and monitor the presence of the virus collectively using techniques to measure 'community viral load'. This article seeks to formulate a critique and propose a novel way of theorizing community viral load. Based on the salient work of Michel Foucault, especially the governmentality literature, this article critically examines the use of community viral load as a new strategy of government. Drawing also on the work of Miller and Rose, this article explores the deployment of 'community' through the re-configuration of space, the problematization of viral concentrations in specific microlocales, and the government (in the Foucauldian sense) of specific bodies which are seen as 'risky', dangerous and therefore, in need of attention. It also examines community viral load as a necessary precondition - forming the 'conditions of possibility' - for the recent shift to high impact prevention tactics that are being scaled up across North America.

  3. Sustainable HIV treatment in Africa through viral-load-informed differentiated care

    DEFF Research Database (Denmark)

    Phillips, Andrew; Shroufi, Amir; Vojnov, Lara

    2015-01-01

    There are inefficiencies in current approaches to monitoring patients on antiretroviral therapy in sub-Saharan Africa. Patients typically attend clinics every 1 to 3 months for clinical assessment. The clinic costs are comparable with the costs of the drugs themselves and CD4 counts are measured...... every 6 months, but patients are rarely switched to second-line therapies. To ensure sustainability of treatment programmes, a transition to more cost-effective delivery of antiretroviral therapy is needed. In contrast to the CD4 count, measurement of the level of HIV RNA in plasma (the viral load......) provides a direct measure of the current treatment effect. Viral-load-informed differentiated care is a means of tailoring care so that those with suppressed viral load visit the clinic less frequently and attention is focussed on those with unsuppressed viral load to promote adherence and timely switching...

  4. Remission of bronchial asthma after viral clearance in chronic hepatitis C

    Institute of Scientific and Technical Information of China (English)

    Norihiko Yamamoto; Kazumoto Murata; Takeshi Nakano

    2005-01-01

    A 53-year-old man with a history of blood transfusion at the age of 20 was admitted to our hospital because of liver dysfunction. He had bronchial asthma when he was 18 years old, which naturally resolved within 2 years. However, his bronchial asthma recurred at the age of 45 and was treated with oral theophylline. He was diagnosed as having chronic hepatitis C based on the histological and clinical findings, and then interferon (IFN) therapy was administered. The frequency of bronchial asthma attack was gradually decreasing after IFN therapy with marked improvement of hypereosinophilia. He achieved sustained viral response (SVR) and his bronchial asthma did not worsen even after the cessation of IFN. Hepatitis C virus (HCV) infection and IFN therapy were considered in the remission of asthma in this case. HCV infection could be the cause of bronchial asthma, especially in patients with late appearance of asthma.

  5. Sustainable HIV treatment in Africa through viral-load-informed differentiated care.

    Science.gov (United States)

    Phillips, Andrew; Shroufi, Amir; Vojnov, Lara; Cohn, Jennifer; Roberts, Teri; Ellman, Tom; Bonner, Kimberly; Rousseau, Christine; Garnett, Geoff; Cambiano, Valentina; Nakagawa, Fumiyo; Ford, Deborah; Bansi-Matharu, Loveleen; Miners, Alec; Lundgren, Jens D; Eaton, Jeffrey W; Parkes-Ratanshi, Rosalind; Katz, Zachary; Maman, David; Ford, Nathan; Vitoria, Marco; Doherty, Meg; Dowdy, David; Nichols, Brooke; Murtagh, Maurine; Wareham, Meghan; Palamountain, Kara M; Chakanyuka Musanhu, Christine; Stevens, Wendy; Katzenstein, David; Ciaranello, Andrea; Barnabas, Ruanne; Braithwaite, R Scott; Bendavid, Eran; Nathoo, Kusum J; van de Vijver, David; Wilson, David P; Holmes, Charles; Bershteyn, Anna; Walker, Simon; Raizes, Elliot; Jani, Ilesh; Nelson, Lisa J; Peeling, Rosanna; Terris-Prestholt, Fern; Murungu, Joseph; Mutasa-Apollo, Tsitsi; Hallett, Timothy B; Revill, Paul

    2015-12-01

    There are inefficiencies in current approaches to monitoring patients on antiretroviral therapy in sub-Saharan Africa. Patients typically attend clinics every 1 to 3 months for clinical assessment. The clinic costs are comparable with the costs of the drugs themselves and CD4 counts are measured every 6 months, but patients are rarely switched to second-line therapies. To ensure sustainability of treatment programmes, a transition to more cost-effective delivery of antiretroviral therapy is needed. In contrast to the CD4 count, measurement of the level of HIV RNA in plasma (the viral load) provides a direct measure of the current treatment effect. Viral-load-informed differentiated care is a means of tailoring care so that those with suppressed viral load visit the clinic less frequently and attention is focussed on those with unsuppressed viral load to promote adherence and timely switching to a second-line regimen. The most feasible approach to measuring viral load in many countries is to collect dried blood spot samples for testing in regional laboratories; however, there have been concerns over the sensitivity and specificity of this approach to define treatment failure and the delay in returning results to the clinic. We use modelling to synthesize evidence and evaluate the cost-effectiveness of viral-load-informed differentiated care, accounting for limitations of dried blood sample testing. We find that viral-load-informed differentiated care using dried blood sample testing is cost-effective and is a recommended strategy for patient monitoring, although further empirical evidence as the approach is rolled out would be of value. We also explore the potential benefits of point-of-care viral load tests that may become available in the future.

  6. Delayed Viral Clearance after 6-Week Treatment with Peginterferon Plus Ribavirin in a Patient with Chronic Hepatitis C Virus Genotype 1b

    OpenAIRE

    Akira Sato; Toshiya Ishii; Kayo Adachi; Hideaki Takahashi; Fumiaki Sano; Nobuyuki Matsumoto

    2016-01-01

    Following interferon-based therapy for chronic hepatitis C, the negativity of hepatitis C virus RNA is essential to achieve viral clearance at the end of treatment. We report a case of clearance of chronic hepatitis C virus infection following early discontinuation (at 6 weeks) of peginterferon plus ribavirin therapy, without negativity for hepatitis C virus RNA during the treatment period. The patient was a 76-year-old Japanese male infected with hepatitis C virus genotype 1b and TT of IL28B...

  7. Sustainable HIV Treatment in Africa through Viral Load-Informed Differentiated Care

    Science.gov (United States)

    Phillips, Andrew; Shroufi, Amir; Vojnov, Lara; Cohn, Jennifer; Roberts, Teri; Ellman, Tom; Bonner, Kimberly; Rousseau, Christine; Garnett, Geoff; Cambiano, Valentina; Nakagawa, Fumiyo; Ford, Deborah; Bansi-Matharu, Loveleen; Miners, Alec; Lundgren, Jens; Eaton, Jeff; Parkes-Ratanshi, Rosalind; Katz, Zachary; Maman, David; Ford, Nathan; Vitoria, Marco; Doherty, Meg; Dowdy, David; Nichols, Brooke; Murtagh, Maurine; Wareham, Meghan; Palamountain, Kara; Musanhu, Christine Chiedza; Stevens, Wendy; Katzenstein, David; Ciaranello, Andrea; Barnabas, Ruanne; Braithwaite, Scott; Bendavid, Eran; Nathoo, Kusum J; van de Vijver, David; Wilson, David; Holmes, Charles; Bershteyn, Anna; Walker, Simon; Raizes, Elliot; Jani, Ilesh; Nelson, Lisa; Peeling, Rosanna; Terris-Prestholt, Fern; Murungu, Joseph; Mutasa-Apollo, Tsitsi; Hallett, Timothy; Revill, Paul

    2016-01-01

    There are inefficiencies in current approaches to monitoring patients on antiretroviral therapy (ART) in sub-Saharan Africa. Patients typically attend clinics every 1–3 months for clinical assessment, with clinic costs being comparable with costs of drugs themselves, CD4 counts are measured every 6 months, yet patients are rarely switched to second-line therapies. To ensure sustainability of treatment programmes a transition to more cost-effective ART deliver is needed. In contrast to the CD4 count, measurement of the level of HIV RNA in plasma (“viral load”) provides a direct measure of current treatment effect. Viral load informed differentiated care is a means of tailoring care whereby those with suppressed viral load have less frequent clinical visits and attention is paid to those with unsuppressed viral load to promote adherence and timely switching to a second-line regimen. The most feasible approach in many countries to measure viral load is by collecting dried blood spot (DBS) samples for testing in regional laboratories, although there have been concerns over the sensitivity/specificity of DBS to define treatment failure and the delay in receiving results. We use modelling to synthesize available evidence and evaluate the cost-effectiveness of viral load-informed differentiated care, account for limitations of DBS. We find that viral load-informed differentiated care using DBS is expected to be cost-effective and is recommended as the strategy for patient monitoring, although further empirical evidence as the approach is rolled out would be of value. We also explore the potential benefits of future availability of point-of-care (POC) viral load tests. PMID:26633768

  8. Tip clearance effects on loads and performances of semi-open impeller centrifugal pumps at different specific speeds

    Science.gov (United States)

    Boitel, G.; Fedala, D.; Myon, N.

    2016-11-01

    Relevant industrial standards or customer's specifications could strictly forbid any device adjusting the axial rotor/stator position, so that tip clearance between semi-open impeller and casing might become a result of the pump machining tolerances and assembling process, leading to big tip clearance variations compared to its nominal value. Consequently, large disparities of global performances (head, power, efficiency) and axial loads are observed with high risk of both specifications noncompliance and bearing damages. This work aims at quantifying these variations by taking into account tip clearance value and pump specific speed. Computational Fluid Dynamics is used to investigate this phenomenon by means of steady simulations led on a semi-open centrifugal pump numerical model including secondary flows, based on a k-omega SST turbulence model. Four different specific speed pump sizes are simulated (from 8 to 50, SI units), with three tip clearances for each size on a wide flow range (from 40% to 120% of the best efficiency point). The numerical results clearly show that head, power and efficiency increase as the tip clearance decreases for the whole flow range. This effect is more significant when the specific speed is low. Meanwhile, the resulting axial thrust on the impeller is very sensitive to the tip clearance and can even lead to direction inversion.

  9. Multigene tracking of quasispecies in viral persistence and clearance of hepatitis C virus

    Institute of Scientific and Technical Information of China (English)

    Song Chen; Yu-Ming Wang

    2005-01-01

    AIM: To investigate the evaluation of hepatitis C virus (HCV) quasispecies in the envelope region and its relationship with the outcome of acute hepatitis C. METHODS: HCV quasispecies were characterized in specimens collected every 2-6 mo from a cohort of acutely HCV-infected subjects. We evaluated two individuals who spontaneously cleared viremia and three individuals with persistent viremia by cloning 33 1-kb amplicons that spanned E1 and the 5' half of E2, including hypervariable region 1 (HVR1). To assess the quasispecies complexity and to detect variants for sequencing, 33 cloned cDNAs representing each specimen were assessed bya combined method of analysis of a single-stranded conformational polymorphism and heteroduplex analysis. The rates of both synonymous and nonsynonymous substitutions for the E1, HVR1 and E2 regions outside HVR1 were analyzed.RESULTS: Serum samples collected from chronic phase of infection had higher quasispecies complexity than those collected from acute phase of infection in all individuals examined. The genetic diversity (genetic distance) within HVR1 was consistently higher than that in the complete E1 (0.0322±0.0068 vs-0.0020±0.0014, P<0.05) and E2 regions outside HVR1 (0.0322±0.0068 vs0.0017±0.0011, P<0.05) in individuals with persistent viremia, but did not change markedly over time in those with clearance of viremia. For individuals with persistent viremia, the rate of nonsynonymous substitutions within the HVR1 region (2.76×10-3±1.51×10-3) predominated and gradually increased, as compared with that in the E1 and E2 regions outside HVR1 (0.23×10-3±0.15×10-3, 0.50×10-3±0.10×10-3).By contrast, the rates of both nonsynonymous and synonymous substitutions for the E1 and E2 regions including HVR1 were consistently lower in individuals withclearance of viremia. CONCLUSION: HCV persistence is associated with a complexity quasispecies and positive selection of HVR1by the host immune system.

  10. HPV infection, risk factors and viral load among Mexican male college students

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    Carmina Vera-Uehara

    2014-01-01

    Full Text Available Objectives: To determine the prevalence of HPV and the risky sexual behaviors associated to it in a sample of male college students, taking into account genotype and viral load. Methods: From 2002 to 2003, male students from the Autonomous University of Morelos State completed a questionnaire and provided self-collected genital samples to detect and quantify HPV. We performed a bivariate and a multivariate logistic regression analysis to identify correlates associated with the infection and to assess the viral load as a function of the viral infecting type. The fragments of β-globin gene and L1 of HPV, were amplified, purified and cloned, to evaluate viral load. Results: Among 253 subjects, HPV prevalence was 19.4%, and HPV16 was the most common subtype. History of STIs (OR = 4.8; 95% CI 1.2–18.9, contraceptive pill use by female partner (OR = 2.6; 95% CI 1.1–6.3 and exchanging sex for money (OR = 4.9; 95% CI 1.2–20 were associated to the HPV infection. HPV16 viral load was 7.8 copies (HPV/beta-globin compared to 0.9 copies for other HPV types. Discussion: HPV16 displayed the highest viral load, and it was the most prevalent. It was found that using contraceptive pills by female partners was associated with HPV infection.

  11. Antiretroviral treatment, viral load of mothers & perinatal HIV transmission in Mumbai, India

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    Swati P Ahir

    2013-01-01

    Full Text Available Background & objectives: Mother-to-child transmission (MTCT is the most significant route of HIV transmission in children below the age of 15 yr. In India, perinatal HIV transmission, even after treatment, accounts for 5.4 per cent of HIV cases. The present study was conducted to evaluate the efficacy of anti-retro viral therapy (ART or prophylactic treatment (PT to control maternal viral load in HIV positive women, and its effect on vertical HIV transmission to their infants. Methods: A total of 58 HIV positive women were enrolled at the time of delivery and their plasma samples were obtained within 24 h of delivery for estimation of viral load. Viral load analysis was completed in 38 women. Infants received single dose nevirapine within 2 h of birth and zidovudine for 6 wk. At the end of 18 month follow up, HIV positive or negative status was available in 28 infants. Results: Results revealed undetectable levels of viral load in 58.3 per cent of women with ART compared to 30.7 per cent of women with PT. No women on ART had viral load more than 10,000 copies/ml, whereas seven (26.9%, P=0.07 women receiving PT had this viral load. Median CD4 count of women on PT (483 cells/μl was high compared to the women on ART (289 cells/ μl. At the end of 18 months follow up, only two children were HIV positive, whose mothers were on PT. One had in utero transmission; infection detected within 48 h of delivery, while the other child was infected post partum as HIV was detected at six months follow up. Interpretation & conclusions: Women who received a single dose of nevirapine during delivery had higher levels of viral load than women on ART. Combination drug therapy for pregnant women is now a standard of care in most of the western countries; use of nevirapine monotherapy at the time of delivery in our settings is not effective in controlling viral load. This highlights initiation of ART in pregnant women to control their viral load and thus to inhibit

  12. Variables that influence HIV-1 cerebrospinal fluid viral load in cryptococcal meningitis: a linear regression analysis

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    Cecchini Diego M

    2009-11-01

    Full Text Available Abstract Background The central nervous system is considered a sanctuary site for HIV-1 replication. Variables associated with HIV cerebrospinal fluid (CSF viral load in the context of opportunistic CNS infections are poorly understood. Our objective was to evaluate the relation between: (1 CSF HIV-1 viral load and CSF cytological and biochemical characteristics (leukocyte count, protein concentration, cryptococcal antigen titer; (2 CSF HIV-1 viral load and HIV-1 plasma viral load; and (3 CSF leukocyte count and the peripheral blood CD4+ T lymphocyte count. Methods Our approach was to use a prospective collection and analysis of pre-treatment, paired CSF and plasma samples from antiretroviral-naive HIV-positive patients with cryptococcal meningitis and assisted at the Francisco J Muñiz Hospital, Buenos Aires, Argentina (period: 2004 to 2006. We measured HIV CSF and plasma levels by polymerase chain reaction using the Cobas Amplicor HIV-1 Monitor Test version 1.5 (Roche. Data were processed with Statistix 7.0 software (linear regression analysis. Results Samples from 34 patients were analyzed. CSF leukocyte count showed statistically significant correlation with CSF HIV-1 viral load (r = 0.4, 95% CI = 0.13-0.63, p = 0.01. No correlation was found with the plasma viral load, CSF protein concentration and cryptococcal antigen titer. A positive correlation was found between peripheral blood CD4+ T lymphocyte count and the CSF leukocyte count (r = 0.44, 95% CI = 0.125-0.674, p = 0.0123. Conclusion Our study suggests that CSF leukocyte count influences CSF HIV-1 viral load in patients with meningitis caused by Cryptococcus neoformans.

  13. Effects of interferon-α/β on HBV replication determined by viral load.

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    Yongjun Tian

    2011-07-01

    Full Text Available Interferons α and β (IFN-α/β are type I interferons produced by the host to control microbial infections. However, the use of IFN-α to treat hepatitis B virus (HBV patients generated sustained response to only a minority of patients. By using HBV transgenic mice as a model and by using hydrodynamic injection to introduce HBV DNA into the mouse liver, we studied the effect of IFN-α/β on HBV in vivo. Interestingly, our results indicated that IFN-α/β could have opposite effects on HBV: they suppressed HBV replication when viral load was high and enhanced HBV replication when viral load was low. IFN-α/β apparently suppressed HBV replication via transcriptional and post-transcriptional regulations. In contrast, IFN-α/β enhanced viral replication by inducing the transcription factor HNF3γ and activating STAT3, which together stimulated HBV gene expression and replication. Further studies revealed an important role of IFN-α/β in stimulating viral growth and prolonging viremia when viral load is low. This use of an innate immune response to enhance its replication and persistence may represent a novel strategy that HBV uses to enhance its growth and spread in the early stage of viral infection when the viral level is low.

  14. Physical status and viral load in women with positive human papillomavirus (HPV) infection in uterine cervix

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Byoung Gie; Lee, Eui Don; Zin, Yong Jae [Korea Cancer Center Hospital, Seoul (Korea, Republic of)

    1998-01-01

    This study was performed to determine the frequency of viral integration and viral load in women with positive HPV type 16 infection, and showing normal findings, CIN, and cervical cancer. Total 75 (normal, 15; CIN I, 20; CIN III, 20; cervical cancer, 20) cervical swab specimens were used. HPV detection, typing, and viral load was determined by PCR method. Seventy of 75 (93.3%) of cervical swab specimens showed same results with hybrid capture assay and PCR method for detecting HPV DNA. HPV type 16 DNA was identified more frequently with progression from normal to cervical cancer (normal, 13 %; CIN I, 15%; CIN III, 40 %; cervical cancer, 55 %). The frequency of HPV type 16 DNA integration also increased with grade of the lesion (normal, 0 %; CIN I, 33 %; CIN III, 87 %; cervical cancer, 91 %) suggesting most of HPV type 16 present as integration forms in the cells. In addition, high-level of HPV 16 viral load also was found more frequently in CIN III and cervical cancer (normal, 0 %; CIN I, 0 %; CIN III, 87 %; cervical cancer, 100 %). These results suggest that viral integration and high-level of viral load may play an important role in cervical carcinogenesis. (author). 13 refs., 5 figs.

  15. Correlation analysis of high-risk human papillomavirus viral load and cervical lesions

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    Xiao-xing MA

    2012-05-01

    Full Text Available Objective  To explore the association between high-risk human papillomavirus (HR-HPV viral load and pathological grades of cervical intraepithelial neoplasia (CIN and cervical cancer. Methods  A total of 1248 patients from General Hospital of PLA, who underwent colposcopy and surgery due to cervical lesions between Jan. 2006 and Aug. 2011 were enrolled in this study, and they were divided five groups: cervicitis, CIN Ⅰ, CIN Ⅱ-Ⅲ, stage Ⅰ cervical cancer and stage Ⅱ cervical cancer. HR-HPV viral load (RLU/CO was determined by the Hybrid Capture Ⅱ (HCⅡ system, and they were categorized into five groups: 0-0.99, 1.00-9.99, 10.00-99.99, 100.00-999.99, ≥1000.00. The mean value and standard deviation of different HR-HPV viral load in the patients with cervicitis or with CIN Ⅰ, CINⅡ-Ⅲ, stage Ⅰ cervical cancer or stage Ⅱ cervical cancer were compared, and the correlation of HR-HPV viral load and pathogenesis of cervical lesions was analyzed. Results  HPV viral loads were significantly higher in CINⅠ(842.1±983.9, CINⅡ-Ⅲ (690.1±795.0, stage Ⅰ cervical cancer (893.1±974.2 and stage Ⅱ cervical cancer (699.5±908.3 patients than in cervicitis patients (274.2±613.6, P < 0.05, and the HPV viral loads in CINⅠ(842.1±983.9 and stage Ⅰ cervical cancer patients were higher than those in CINⅡ-Ⅲ patients (P < 0.05. When HR-HPV viral load was ≥100RLU/CO, the risk of CIN and cervical cancer increased with the increase in viral load, but there was no correlation between the viral load and pathological grades of cervical lesions. In the patients with stage ⅠB-Ⅱ cervical squamous cell carcinoma, when the HR-HPV viral load was ≥100RLU/CO, the risk of lymph node metastasis increased (P < 0.05, and the number of patients with maximum diameter of the cervical tumor ≥4cm also increased (P < 0.05. However, the HR-HPV viral load was not correlated with patient age, pathological type of the lesion, depth of cancer

  16. Impact of collection method on assessment of semen HIV RNA viral load.

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    Brendan J W Osborne

    Full Text Available BACKGROUND: The blood HIV RNA viral load is the best-defined predictor of HIV transmission, in part due to ease of measurement and the correlation of blood and genital tract (semen or cervico-vaginal viral load, although recent studies found semen HIV RNA concentration to be a stronger predictor of HIV transmission. There is currently no standardized method for semen collection when measuring HIV RNA concentration. Therefore, we compared two collection techniques in order to study of the impact of antiretroviral therapy on the semen viral load. METHODOLOGY/PRINCIPAL FINDINGS: Semen was collected by masturbation from HIV-infected, therapy-naïve men who have sex with men (MSM either undiluted (Visit 1 or directly into transport medium (Visit 2. Seminal plasma was then isolated, and the HIV RNA concentration obtained with each collection technique was measured and corrected for dilution if necessary. Collection of semen directly into transport medium resulted in a median HIV RNA viral load that was 0.4 log10 higher than undiluted samples. CONCLUSIONS/SIGNIFICANCE: The method of semen collection is an important consideration when quantifying the HIV RNA viral load in this compartment.

  17. Distinct patterns of the lipid alterations between genotype 1 and 2 chronic hepatitis C patients after viral clearance.

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    Ming-Ling Chang

    Full Text Available The hepatitis C virus (HCV genotype-specific impacts on the host metabolic alterations remained inconclusive.A prospective study including 229 (118 genotype 1 (G1 and 111 G2 consecutive chronic HCV patients who had completed a course of anti-HCV treatment and underwent pre- and 24 weeks post-treatment surveys of metabolic profiles was conducted. Patients were stratified according to the therapeutic response, viral genotype and baseline insulin resistance (IR: homeostasis model assessments of IR (HOMA-IR ≥ 2.5. Paired t-tests were used to compare the pre- and post-treatment variables.Significant post-therapeutic increases in cholesterol, triglyceride, HDL, LDL, apolipoprotein A1 and apolipoprotein B were observed in patients with sustained virological response (SVR but not in those without. Among those with SVR, post-therapeutic increases in HDL (p<0.001 and apolipoprotein A1 (p = 0.012 were only found in G2, whereas increased triglyceride/HDL (p = 0.01 ratios were only found in G1 patients. When stratified by baseline IR among those with SVR, a significant increase in post-treatment HDL (p = 0.019 and apolipoprotein A1 (p = 0.012 but a decrease in HOMA-IR (p = 0.04, C-peptide (p = 0.019 and hemoglobin A1c (p = 0.047 were found in patients with baseline IR; a significant increase in HOMA-IR (p = 0.002 was found in patients without baseline IR. The latter change was observed only in G1 (p = 0.01 but not G2 patients. Although the pre-treatment metabolic profiles of G1 and G2 patients were indifferent, G1 had higher post-treatment triglyceride/HDL ratios (p = 0.041 and triglyceride (p = 0.044 levels than G2 patients.G2 benefit more than G1 patients from viral clearance in metabolic alterations, particularly in those without baseline IR.

  18. 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

  19. DNA-guided hepatitis B treatment: Viral load is insufficient with few exceptions

    Institute of Scientific and Technical Information of China (English)

    Pankaj Jain

    2009-01-01

    In DNA-guided hepatitis B treatment, viral load is insufficient, and requires other viral markers for treatment of hepatitis B patients as in patients with acute exacerbation of chronic hepatitis B, end-stage renal disease on dialysis, human immunodeficiency virus co-infected patients. There are exceptions to this rule:a residual level hepatitis B virus (HBV) DNA at 24 wk predicts beneficial outcome and reduced resistance at 1 year. The genotypic viral resistance to antiviral agents and occult HBV infection can be determined by HBV-DNA levels.

  20. Honeybee (Apis mellifera Venom Reinforces Viral Clearance during the Early Stage of Infection with Porcine Reproductive and Respiratory Syndrome Virus through the Up-Regulation of Th1-Specific Immune Responses

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    Jin-A Lee

    2015-05-01

    Full Text Available Porcine reproductive and respiratory syndrome (PRRS is a chronic and immunosuppressive viral disease that is responsible for substantial economic losses for the swine industry. Honeybee venom (HBV is known to possess several beneficial biological properties, particularly, immunomodulatory effects. Therefore, this study aimed at evaluating the effects of HBV on the immune response and viral clearance during the early stage of infection with porcine reproductive and respiratory syndrome virus (PRRSV in pigs. HBV was administered via three routes of nasal, neck, and rectal and then the pigs were inoculated with PRRSV intranasally. The CD4+/CD8+ cell ratio and levels of interferon (IFN-γ and interleukin (IL-12 were significantly increased in the HBV-administered healthy pigs via nasal and rectal administration. In experimentally PRRSV-challenged pigs with virus, the viral genome load in the serum, lung, bronchial lymph nodes and tonsil was significantly decreased, as was the severity of interstitial pneumonia, in the nasal and rectal administration group. Furthermore, the levels of Th1 cytokines (IFN-γ and IL-12 were significantly increased, along with up-regulation of pro-inflammatory cytokines (TNF-α and IL-1β with HBV administration. Thus, HBV administration—especially via the nasal or rectal route—could be a suitable strategy for immune enhancement and prevention of PRRSV infection in pigs.

  1. Evaluation of viral clearance in the production of HPV-16 L1 virus-like particles purified from insect cell cultures.

    Science.gov (United States)

    Jeong, Hye-Sung; Shin, Jin-Ho; Choi, Jung-Yun; Kim, Young-Lim; Bae, Jei-Jun; Kim, Byoung-Guk; Ryu, Seung-Rel; Kim, Soon-Nam; Min, Hong-Ki; Kim, Hong-Jin; Park, Sue-Nie

    2006-12-01

    Biopharmaceutical products produced from cell cultures have a potential for viral contamination from cell sources or from adventitious introduction during production. The objective of this study was to assess viral clearance in the production of insect cell-derived recombinant human papillomavirus (HPV)-16 type L1 virus-like particles (VLPs). We selected Japanese encephalitis virus (JEV), bovine viral diarrhea virus (BVDV), and minute virus of mice (MVM) as relevant viruses to achieve the aim of this study. A downstream process for the production of purified HPV-16 L1 VLPs consisted of detergent lysis of harvested cells, sonication, sucrose cushion centrifugation, and cesium chloride (CsCl) equilibrium density centrifugation. The capacity of each purification/treatment step to clear viruses was expressed as reduction factor by measuring the difference in log virus infectivity of sample pools before and after each process. As a result, detergent treatment (0.5% v/v, Nonidet P-40/phosphate-buffered saline) was effective for inactivating enveloped viruses such as JEV and BVDV, but no significant reduction ( or = 4.40 log(10) reductions). Given the study conditions we used, overall cumulative reduction factors for clearance of JEV, BVDV, and MVM were > or = 10.50, > or = 9.20, and > or = 6.40 log(10) in 150 ml of starting cell cultures, respectively.

  2. IL28B polymorphisms influence stage of fibrosis and spontaneous or interferon-induced viral clearance in thalassemia patients with hepatitis C virus infection

    Science.gov (United States)

    Di Marco, Vito; Bronte, Fabrizio; Calvaruso, Vincenza; Capra, Marcello; Borsellino, Zelia; Maggio, Aurelio; Renda, Maria Concetta; Pitrolo, Lorella; Lo Pinto, Maria Carmela; Rizzo, Michele; Fiorenza, Flavia; Gerardi, Calogera; Grimaudo, Stefania; Di Cristina, Antonietta; Levrero, Massimo; Craxì, Antonio

    2012-01-01

    Background Polymorphisms in the interleukin-28B are important determinants in the spontaneous and drug-induced control of hepatitis C virus infection. Design and Methods We assessed the association of rs8099917 and rs12979860 polymorphisms with spontaneous viral clearance, severity of liver fibrosis, and response to interferon-monotherapy in 245 thalassemia major patients with hepatitis C virus infection. Results Ninety-eight patients (40%) had a spontaneous viral clearance while 147 patients (60%) developed a chronic infection. Spontaneous viral clearance was more frequent among patients with the T/T genotype of rs8099917 polymorphism (OR 2.130; P=0.008) or C/C genotype of rs12979860 polymorphism (OR 2.425; P=0.001). During observation, 131 patients with chronic infection underwent a liver biopsy; age (OR 1.058; P=0.01) G/T or G/G genotypes of rs8099917 polymorphism (OR 3.962; P=0.001), and C/T or T/T genotypes of rs12979860 polymorphism (OR 3.494; P=0.005) were associated with severe liver fibrosis, independent of liver iron concentration. Finally, T/T genotype of rs8099917 polymorphism (OR 3.014; P=0.03) or C/C genotype of rs12979860 polymorphism (OR 3.285; P=0.01), age (OR 0.902; P=0.001), female gender (OR 3.418; P=0.01) and 2 or 3 virus C genotypes (OR 4.700; P=0.007) were independently associated with sustained virological response in 114 patients treated with alpha-interferon. Conclusions Polymorphisms in the interleukin-28B are associated with the control of hepatitis C virus infection in thalassemia major patients, and understanding allelic patterns has an important role in determining prognosis and therapeutic management. PMID:22180419

  3. Antigen-loaded ER microsomes from APC induce potent immune responses against viral infection.

    Science.gov (United States)

    Sofra, Vassiliki; Mansour, Salah; Liu, Mengya; Gao, Bin; Primpidou, Elisavet; Wang, Ping; Li, Suling

    2009-01-01

    Although matured DC are capable of inducing effective primary and secondary immune responses in vivo, it is difficult to control the maturation and antigen loading in vitro. In this study, we show that ER-enriched microsomal membranes (microsomes) isolated from DC contain more peptide-receptive MHC I and II molecules than, and a similar level of costimulatory molecules to, their parental DC. After loading with defined antigenic peptides, the microsomes deliver antigenic peptide-MHC complexes (pMHC) to both CD4 and CD8 T cells effectively in vivo. The peptide-loaded microsomes accumulate in peripheral lymphoid organs and induce stronger immune responses than peptide-pulsed DC. The microsomal vaccines protect against acute viral infection. Our data demonstrate that peptide-MHC complexes armed microsomes from DC can be an important alternative to DC-based vaccines for protection from viral infection.

  4. Performance of a Taqman Assay for Improved Detection and Quantification of Human Rhinovirus Viral Load

    Science.gov (United States)

    Ng, Kim Tien; Chook, Jack Bee; Oong, Xiang Yong; Chan, Yoke Fun; Chan, Kok Gan; Hanafi, Nik Sherina; Pang, Yong Kek; Kamarulzaman, Adeeba; Tee, Kok Keng

    2016-01-01

    Human rhinovirus (HRV) is the major aetiology of respiratory tract infections. HRV viral load assays are available but limitations that affect accurate quantification exist. We developed a one-step Taqman assay using oligonucleotides designed based on a comprehensive list of global HRV sequences. The new oligonucleotides targeting the 5′-UTR region showed high PCR efficiency (E = 99.6%, R2 = 0.996), with quantifiable viral load as low as 2 viral copies/μl. Assay evaluation using an External Quality Assessment (EQA) panel yielded a detection rate of 90%. When tested on 315 human enterovirus-positive specimens comprising at least 84 genetically distinct HRV types/serotypes (determined by the VP4/VP2 gene phylogenetic analysis), the assay detected all HRV species and types, as well as other non-polio enteroviruses. A commercial quantification kit, which failed to detect any of the EQA specimens, produced a detection rate of 13.3% (42/315) among the clinical specimens. Using the improved assay, we showed that HRV sheds in the upper respiratory tract for more than a week following acute infection. We also showed that HRV-C had a significantly higher viral load at 2–7 days after the onset of symptoms (p = 0.001). The availability of such assay is important to facilitate disease management, antiviral development, and infection control. PMID:27721388

  5. Quantification of infectious HIV-1 plasma viral load using a boosted in vitro infection protocol.

    Science.gov (United States)

    Rusert, Peter; Fischer, Marek; Joos, Beda; Leemann, Christine; Kuster, Herbert; Flepp, Markus; Bonhoeffer, Sebastian; Günthard, Huldrych F; Trkola, Alexandra

    2004-08-15

    Methods currently used for HIV-1 viral load measurements are very sensitive, but cannot distinguish between infectious and noninfectious particles. Here we describe the development of a novel, sensitive, and highly reproducible method that allows rapid isolation and quantification of infectious particles from patient plasma. By immobilizing HIV-1 particles in human plasma to platelets using polybrene, we observed a 10- to 1000-fold increase in infectivity over infection protocols using free virus particles. Using this method, we evaluated infectivity in plasma from 52 patients at various disease stages. At plasma viral loads of 1000-10000 HIV-1 RNA copies/ml 18%, at 10,000-50,000 copies/ml 73%, at 50,000-100,000 copies/ml 90%, and above 100,000 copies 96% of cultures were positive. We found that infectious titers among patients vary distinctively but are characteristic for a patient over extended time periods. Furthermore, we demonstrate that by evaluating infectious titers in conjunction with total HIV RNA loads, subtle effects of treatment intervention on viremia levels can be detected. The immobilization procedure does not interfere with viral entry and does not restore the infectivity of neutralized virus. Therefore, this assay system can be utilized to investigate the influence of substances that specifically affect virion infectivity such as neutralizing antibodies, soluble CD4, or protease inhibitors. Measuring viral infectivity may thereby function as an additional, useful marker in monitoring disease progression and evaluating efficacy of antivirals in vivo.

  6. Hepatitis A viral load in relation to severity of the infection.

    Science.gov (United States)

    Fujiwara, Keiichi; Kojima, Hiroshige; Yasui, Shin; Okitsu, Koichiro; Yonemitsu, Yutaka; Omata, Masao; Yokosuka, Osamu

    2011-02-01

    A correlation between hepatitis A virus (HAV) genomes and the clinical severity of hepatitis A has not been established. The viral load in sera of hepatitis A patients was examined to determine the possible association between hepatitis A severity and HAV replication. One hundred sixty-four serum samples from 91 Japanese patients with sporadic hepatitis A, comprising 11 patients with fulminant hepatitis, 10 with severe acute hepatitis, and 70 with self-limited acute hepatitis, were tested for HAV RNA. The sera included 83 serial samples from 20 patients. Viral load was measured by real-time RT-PCR. The detection rates of HAV RNA from fulminant, severe acute, and acute hepatitis were 10/11 (91%), 10/10 (100%), and 55/70 (79%), respectively. Mean values of HAV RNA at admission were 3.48 ± 1.30 logcopies/ml in fulminant, 4.19 ± 1.03 in severe acute, and 2.65 ± 1.64 in acute hepatitis. Patients with severe infection such as fulminant hepatitis and severe acute hepatitis had higher initial viral load than patients with less severe infection (P hepatitis after clinical onset (P = 0.19). HAV RNA was detectable quantitatively in the majority of the sera of hepatitis A cases during the early convalescent phase by real-time PCR. Higher initial viral replication was found in severely infected patients. An excessive host immune response might follow, reducing the viral load rapidly as a result of the destruction of large numbers of HAV-infected hepatocytes, and in turn severe disease might be induced.

  7. Development of a modular virus clearance package for anion exchange chromatography operated in weak partitioning mode.

    Science.gov (United States)

    Iskra, Timothy; Sacramo, Ashley; Gallo, Chris; Godavarti, Ranga; Chen, Shuang; Lute, Scott; Brorson, Kurt

    2015-01-01

    Anion exchange chromatography (AEX) operated under weak partitioning mode has been proven to be a powerful polishing step as well as a robust viral clearance step in Pfizer's monoclonal antibody (mAb) platform purification process. A multivariate design of experiment (DoE) study was conducted to understand the impact of operating parameters and feedstream impurity levels on viral clearance by weak partitioning mode AEX. Bacteriophage was used initially as a surrogate for neutral and acidic isoelectric point mammalian viruses (e.g., retrovirus and parvovirus). Five different mAbs were used in the evaluation of process parameters such as load challenge (both product and impurities), load pH, load conductivity, and contact time (bed height and flow-rate). The operating ranges obtained from phage clearance studies and Pfizer's historical data were used to define an appropriate operating range for a subsequent clearance study with model retrovirus and parvovirus. Both phage and virus clearance evaluations included feedstreams containing different levels of impurities such as high molecular mass species (HMMS), host cell proteins (HCPs), and host cell DNA. For all the conditions tested, over 5 log10 of clearance for both retrovirus and parvovirus was achieved. The results demonstrated that weak partitioning mode AEX chromatography is a robust step for viral clearance and has the potential to be included as part of the modular viral clearance approach.

  8. DNA-guided hepatitis B treatment, viral load is essential,but not sufficient

    Institute of Scientific and Technical Information of China (English)

    Rafael Bárcena Marugán; Silvia García Garzón

    2009-01-01

    Hepatitis B virus (HBV) infection is a global public health problem that concerns 350 million people worldwide. Individuals with chronic hepatitis B (CHB) are at increased risk of developing liver cirrhosis,hepat i c de- compensation and hepatocellular carcinoma. To maintain undetectable viral load reduces chronic infection complications. There is no treatment that eradicates HBV infection. Current drugs are expensive, are associated with adverse events, and are of limited efficacy. Current guidelines try to standardize the clinical practice. Nevertheless, controversy remains about management of asymptomatic patients with CHB who are hepatitis B e antigen (HBeAg)-positive with normal alanine aminotransferase, and what is the cut-off value of viral load to distinguish HBeAgnegative CHB patients and inactive carriers. We discuss in detail why DNA level alone is not sufficient to begin treatment of CHB.

  9. Modeling the impact of hepatitis C viral clearance on end-stage liver disease in an HIV co-infected cohort with targeted maximum likelihood estimation.

    Science.gov (United States)

    Schnitzer, Mireille E; Moodie, Erica E M; van der Laan, Mark J; Platt, Robert W; Klein, Marina B

    2014-03-01

    Despite modern effective HIV treatment, hepatitis C virus (HCV) co-infection is associated with a high risk of progression to end-stage liver disease (ESLD) which has emerged as the primary cause of death in this population. Clinical interest lies in determining the impact of clearance of HCV on risk for ESLD. In this case study, we examine whether HCV clearance affects risk of ESLD using data from the multicenter Canadian Co-infection Cohort Study. Complications in this survival analysis arise from the time-dependent nature of the data, the presence of baseline confounders, loss to follow-up, and confounders that change over time, all of which can obscure the causal effect of interest. Additional challenges included non-censoring variable missingness and event sparsity. In order to efficiently estimate the ESLD-free survival probabilities under a specific history of HCV clearance, we demonstrate the double-robust and semiparametric efficient method of Targeted Maximum Likelihood Estimation (TMLE). Marginal structural models (MSM) can be used to model the effect of viral clearance (expressed as a hazard ratio) on ESLD-free survival and we demonstrate a way to estimate the parameters of a logistic model for the hazard function with TMLE. We show the theoretical derivation of the efficient influence curves for the parameters of two different MSMs and how they can be used to produce variance approximations for parameter estimates. Finally, the data analysis evaluating the impact of HCV on ESLD was undertaken using multiple imputations to account for the non-monotone missing data.

  10. Effects of medical male circumcision (MC on plasma HIV viral load in HIV+ HAART naive men; Rakai, Uganda.

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    Godfrey Kigozi

    Full Text Available BACKGROUND: Medical male circumcision (MC of HIV-infected men may increase plasma HIV viral load and place female partners at risk of infection. We assessed the effect of MC on plasma HIV viral load in HIV-infected men in Rakai, Uganda. METHODS: 195 consenting HIV-positive, HAART naïve men aged 12 and above provided blood for plasma HIV viral load testing before surgery and weekly for six weeks and at 2 and 3 months post surgery. Data were also collected on baseline social demographic characteristics and CD4 counts. Change in log10 plasma viral load between baseline and follow-up visits was estimated using paired t tests and multivariate generalized estimating equation (GEE. RESULTS: Of the 195 men, 129 had a CD4 count ≧ 350 and 66 had CD4 <350 cells/mm3. Men with CD4 counts <350 had higher baseline mean log10 plasma viral load than those with CD4 counts ≧ 350 cells/mm3 (4.715 vs 4.217 cps/mL, respectively, p = 0.0005. Compared to baseline, there was no statistically significant increase in post-MC HIV plasma viral loads irrespective of CD4. Multivariate analysis showed that higher baseline log10 plasma viral load was significantly associated with reduction in mean log10 plasma viral load following MC (coef.  = -0.134, p<0.001. CONCLUSION: We observed no increase in plasma HIV viral load following MC in HIV-infected, HAART naïve men.

  11. Decreases in community viral load are accompanied by reductions in new HIV infections in San Francisco.

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    Moupali Das

    Full Text Available BACKGROUND: At the individual level, higher HIV viral load predicts sexual transmission risk. We evaluated San Francisco's community viral load (CVL as a population level marker of HIV transmission risk. We hypothesized that the decrease in CVL in San Francisco from 2004-2008, corresponding with increased rates of HIV testing, antiretroviral therapy (ART coverage and effectiveness, and population-level virologic suppression, would be associated with a reduction in new HIV infections. METHODOLOGY/PRINCIPAL FINDINGS: We used San Francisco's HIV/AIDS surveillance system to examine the trends in CVL. Mean CVL was calculated as the mean of the most recent viral load of all reported HIV-positive individuals in a particular community. Total CVL was defined as the sum of the most recent viral loads of all HIV-positive individuals in a particular community. We used Poisson models with robust standard errors to assess the relationships between the mean and total CVL and the primary outcome: annual numbers of newly diagnosed HIV cases. Both mean and total CVL decreased from 2004-2008 and were accompanied by decreases in new HIV diagnoses from 798 (2004 to 434 (2008. The mean (p = 0.003 and total CVL (p = 0.002 were significantly associated with new HIV cases from 2004-2008. CONCLUSIONS/SIGNIFICANCE: Reductions in CVL are associated with decreased HIV infections. Results suggest that wide-scale ART could reduce HIV transmission at the population level. Because CVL is temporally upstream of new HIV infections, jurisdictions should consider adding CVL to routine HIV surveillance to track the epidemic, allocate resources, and to evaluate the effectiveness of HIV prevention and treatment efforts.

  12. Evaluation of viral load in saliva from patients with chronic hepatitis C infection.

    Science.gov (United States)

    Xavier Santos, Renata L; de Deus, Dayse M V; de Almeida Lopes, Edmundo P; Duarte Coêlho, Maria R C; de Castro, Jurema F L

    2015-01-01

    Hepatitis C virus can be detected in blood and other bodily fluids, such as saliva. The aim of this study was to detect and quantify the HCV-RNA in saliva and plasma from patients with chronic hepatitis C infections, as well as check the level of viral load in sex groups (age, ethnicity and virus subtypes). Whole saliva and blood from 70 patients with chronic hepatitis C infections attended at the department of gastroenterology from University Hospital. The HCV-RNA load was performed by qRT-PCR using Sybr Green I master mix. HCV-RNA was detected in 80% (56/70) of patients in saliva and 92.85% (65/70) in plasma. The median of the viral load in the plasma was of 4.87 log10, and in saliva, it was 3.32log10, (p = 0.0005). Female patients and black patients exhibited a negative correlation between the HCV-RNA load in saliva vs. the HCV-RNA load in plasma (r = -0.3172, CI95% -0.6240 to -0.03736, p = 0.0491) and (r = -0.3141; IC95% -0.6069 to -0.05926; p = 0.0209), respectively. HCV-RNA was detected and quantified in saliva samples, and according to the quantification levels, saliva may be a possible transmission source of HCV, particularly in women and people of black ethnicity who develop chronic HCV infections.

  13. Comparison of asymptomatic and symptomatic rhinovirus infections in university students: incidence, species diversity, and viral load.

    Science.gov (United States)

    Granados, Andrea; Goodall, Emma C; Luinstra, Kathy; Smieja, Marek; Mahony, James

    2015-08-01

    Human rhinovirus (HRV) infections are common but poorly characterized in university students. Thus, we characterized asymptomatic and symptomatic HRV infections by incidence, species diversity, and viral load of 502 university students during September and October of 2010 and 2011 from nasal swabs and electronically submitted symptom questionnaires. We tested all symptomatic students and randomly sampled participants who remained asymptomatic (n=25/week, over 8 weeks each study year) on a weekly basis by real-time PCR and sequenced HRV positives. HRV was identified in 33/400 (8.3%) and 85/92 (92.4%) of the asymptomatic and symptomatic students, respectively. We identified a higher than previously reported rate of HRV-B in both groups, although the distribution of HRV species was similar (P=0.37). Asymptomatic viral load averaged 1.2 log10 copies/mL lower than symptomatic HRV (P<0.001). In conclusion, asymptomatic HRV activity preceded peak symptomatic activity in September and October and was associated with lower viral load.

  14. Spontaneous viral clearance after 6-21 years of hepatitis B and C viruses coinfection in high HBV endemic area

    Institute of Scientific and Technical Information of China (English)

    Chun-Lei Fan; Lai Wei; Dong Jiang; Hong-Song Chen; Yan Gao; Ruo-Bing Li; Yu Wang

    2003-01-01

    AIM: To investigate the clinical and virological course of coinfection by hepatitis B virus (HBV) and hepatitis C virus (HCV) in China.METHODS: We enrolled 40 patients with chronic HBV and HCV coinfection (Group BC), 16 patients with chronic HBV infection (Group B) and 31 patients with chronic HCV infection (Group C). They infected HBV and/or HCV during 1982 to 1989.Sera of all the 87 patients were collected in 1994 and 2002respectively. We detected biochemical and virologic markers and serum HBV DNA and HCV RNA levels of all the patients. Btype ultrasound detection was performed in some patients.RESULTS: In Group BC, 67.5% of the patients cleared HBsAg,and 92.5% of the patients cleared HBeAg. The clearance rate of HBV DNA was 87.5%. There was no significant difference of HBV clearance between Group BC and Group B. In Group BC, 85.7% of males and 47.4% of females cleared HBV, and males were easier to clear HBV (x2=6.686, P=0.010). Such a tendency was also found in Group B. The clearance rate of HCV RNA in Group BC was 87.5%, significantly higher than that in Group C (x2=22.963, P<0.001). Less than 40% of the patients in all groups had elevated liver enzyme values. The highest value of alanine aminotransferase (ALT) was 218 u/L (normal range for ALT is 0-40 u/L). In most patients the ultrasonogram presentations changed mildly.CONCLUSION: The clinical manifestations of patients with HBV/HCV coinfection are mild and occult. High clearance rate of HBV and easy to clear HBV in male patients are the characteristics of HBV infection in adults in China. HBV can inhibit HCV replication, but no evidence has been found in our data that HCV suppresses HBV replication.

  15. Vaccine-induced measles virus-specific T cells do not prevent infection or disease but facilitate subsequent clearance of viral RNA.

    Science.gov (United States)

    Lin, Wen-Hsuan W; Pan, Chien-Hsiung; Adams, Robert J; Laube, Beth L; Griffin, Diane E

    2014-04-15

    Infection with wild-type measles virus (MeV) induces lifelong protection from reinfection, and parenteral delivery of the live attenuated measles vaccine (LAV) also provides protection from measles. The level of neutralizing antibody is a good indicator of protection, but the independent roles of MeV-specific antibody and T cells have not been identified. In this study, macaques immunized with LAV through a nebulizer and a mouthpiece developed MeV-specific T-cell responses but not neutralizing antibodies. Upon challenge with wild-type MeV, these animals developed rashes and viremias similar to those in naive animals but cleared viral RNA from blood 25 to 40 days faster. The nebulizer-immunized animals also had more robust MeV-specific CD4(+) and CD8(+) T-cell responses than the naive animals after challenge, characterized by a higher number and better durability of gamma interferon (IFN-γ)-producing cells. Induction of MeV-specific circulating CD4(+) and CD8(+) T cells capable of producing multiple cytokines correlated with clearance of viral RNA in the nebulizer-immunized macaques. These studies demonstrated that MeV-specific T-cell immunity alone did not prevent measles, but T-cell priming enhanced the magnitude, durability, and polyfunctionality of MeV-specific T cells after challenge infection and correlated with more rapid clearance of MeV RNA. IMPORTANCE The components of vaccine-induced immunity necessary for protection from infection and disease have not been clearly identified for most vaccines. Vaccine development usually focuses on induction of antibody, but T-cell-based vaccines are also under development. The live attenuated measles vaccine (LAV) given subcutaneously induces both T cells and neutralizing antibody and provides solid protection from infection. LAV delivered to the upper respiratory tract through a nebulizer and mouthpiece induced a T-cell response but no neutralizing antibody. These T-cell-primed macaques demonstrated no protection from

  16. Search for the presence of occult hepatitis C in patients with treatment-induced viral clearance using an ultrasensitive assay

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    Dzekova-Vidimliski Pavlina

    2016-01-01

    Full Text Available Introduction. Occult hepatitis C is defined by the presence of virus in the peripheral blood mononuclear cells (PBMCs and/or liver cells, in the absence of serum viremia. Objective. To detect the persistence of occult hepatitis C in hemodialysis (HD patients and patients without renal disease (non-renal with treatment-induced clearance of hepatitis C virus (HCV infection, using assays with a very low detection limit of viremia. Methods. A group of 13 HD patients and a group of 43 non-renal patients, with treatment-induced HCV infection clearance were investigated in the study. The HD patients were treated with pegylated interferon alpha (PEG-IFN-α only, while the non-renal patients were treated with a combination therapy of PEGIFN- α and ribavirin. Detection of a possible persistence of HCV RNA in the PBMCs and plasma samples was assessed by an ultrasensitive reverse transcription polymerase chain reaction (RT-PCR assay (2 IU/ml. Results. HCV RNA was not detected in the PBMCs and plasma samples of HD patients and of non-renal patients, when assessed by the ultrasensitive RT-PCR assay. Conclusion. When a sensitive RT-PCR assay was applied, to determine if treatment induced clearance of HCV infection had been successful, occult hepatitis C could not be detected by an ultrasensitive assay, neither in HD nor in non-renal patients.

  17. Effect of viral load on T-lymphocyte failure in patients with chronic hepatitis B

    Institute of Scientific and Technical Information of China (English)

    Jing You; Hutcha Sriplung; Alan Geater; Virasakdi Chongsuvivatwong; Lin Zhuang; Hong-Ying Chen; Lan Yu; Bao-Zhang Tang; Jun-Hua Huang

    2008-01-01

    AIM:To investigate peripheral T-lymphocyte subpopulation profile and its correlation with hepatitis B virus (HBV) replication in patients with chronic hepatitis B (CHB).METHODS:Distribution of T-lymphocyte subpopulations in peripheral blood was measured by flow cytometry in 206 CHB patients.HBV markers were detected with ELISA.Serum HBV DNA load was assessed with quantitative real-time polymerase chain reaction (PCR).The relationship between HBV replication and variation in peripheral T-cell subsets was analyzed.RESULTS:CHB patients had significantly decreased CD3,and CD4+ cells and CD4+/CD8+ ratio,and increased CD8+ cells compared with uninfected controls (55.44±12.39 vs 71.07±4.76,30.92±7.48 vs 38.94±3.39,1.01±0.49 vs 1.67±0.33,and 34.39±9.22 vs 24.02±4.35;P<0.001,respectively).Univariate analysis showed a similar pattern of these parameters was significantly associated with high viral load,presence of serum hepatitis B e antigen (HBeAg) expression,liver disease severity,history of maternal HBV infection,and young age at HBV infection,all with P<0.01.There was a significant linear relationship between viral load and these parameters of T-lymphocyte subpopulations (linear trend test P<0.001).There was a negative correlation between the levels of CD3+ and CD4+ cells and CD4+/CD8+ ratio and serum level of viral load in CHB patients (r=-0.68,-0.65 and-0.75,all P<0.0001),and a positive correlation between CD8+ cells and viral load (r=0.70,P<0.0001).There was a significant decreasing trend in CD3+ and CD4+ cells and CD4+/CD8+ratio with increasing severity of hepatocyte damage and decreasing age at HBV infection (linear trend test P<0.01).In multiple regression (after adjustment for age at HBV infection,maternal HBV infection status and hepatocyte damage severity) log copies of HBV DNA maintained a highly significant predictive coefficient on T-lymphocyte subpopulations,and was the strongest predictor of variation in CD3+,CD4+,CD8+ cells and CD4+/CD8

  18. HBeAg and not genotypes predicts viral load in patients with hepatitis B in Denmark: a nationwide cohort study

    DEFF Research Database (Denmark)

    Krarup, Henrik Bygum; Andersen, Stig; Madsen, Poul Henning;

    2011-01-01

    To explore the influence of HBV genotype on viral load in patients with HBV infection, and to investigate the relation to gender, age and country of origin or antibodies against hepatitis Be antigen (anti-HBe).......To explore the influence of HBV genotype on viral load in patients with HBV infection, and to investigate the relation to gender, age and country of origin or antibodies against hepatitis Be antigen (anti-HBe)....

  19. HBeAg and not genotypes predicts viral load in patients with hepatitis B in Denmark: A nationwide cohort study

    DEFF Research Database (Denmark)

    Krarup, Henrik; Andersen, Stig; Madsen, Poul Henning;

    2011-01-01

    To explore the influence of HBV genotype on viral load in patients with HBV infection, and to investigate the relation to gender, age and country of origin or antibodies against hepatitis Be antigen (anti-HBe).......To explore the influence of HBV genotype on viral load in patients with HBV infection, and to investigate the relation to gender, age and country of origin or antibodies against hepatitis Be antigen (anti-HBe)....

  20. CSF LPV concentrations and viral load in viral suppressed patients on LPV/r monotherapy given once daily

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    Juan Tiraboschi

    2014-11-01

    Full Text Available Introduction: Plasma trough concentrations of lopinavir (LPV given as LPV/r 800/200 mg once daily (OD are reduced in comparison with 400/100 mg twice daily (BID. While OD dosage of LPV/r is sufficient to achieve viral suppression in plasma, data about drug penetration and viral suppression in central nervous system (CNS is needed, mainly if LPVr is used as maintenance monotherapy strategy in selected patients. The objective of this study was to evaluate CSF HIV-1 RNA and CSF LPV concentrations in patients receiving LPV/r monotherapy OD (LPVrMOD. Material and Methods: This is a cross-sectional sub-study within a prospective, open-label pilot simplification study to evaluate the efficacy and safety of LPV/rMOD in virologically suppressed patients previously receiving a BID LPV/r monotherapy regimen (LPV/rMBID, the “Kmon study” (NCT01581853. To assess LPV concentrations and HIV-1 RNA in CSF, a lumbar puncture (LP was performed in a subgroup of patients after at least one month of LPVrMOD treatment. Plasma-paired samples of all patients were also obtained. HIV-1 RNA was determined by real-time PCR (limit of detection 40 copies/mL. Liquid chromatography-tandem mass spectrometry (Tandem labs, NJ was used to determine CSF and blood plasma LPV concentrations. Results: Nine patients were included. Median (range age was 48 (34–56 years, median CD4 cell count 672 (252–1,408 cells/mL, median nadir CD4 count 125 (35–537 cells/mL and 40% of subjects were HCV-positive. Before starting LPV/rMOD median time on a LPV/r-containing regimen and on LPV/rMBID were 9 (4–11 years and 15 (7–24 months respectively, median time with undetectable HIV viral load was 5 (3–12 years and 2 patients had a previous documented blip. LP was performed a median of 24 (8–36 weeks after starting LPV/rMOD and 24 (11–28 hours after the last LPV/rMOD dose CSF and plasma HIV RNA was 40 copies/mL in all patients. Median LPV CSF concentration was 9.78 (1.93–78.3 ng

  1. Lack of association between viral load and severity of acute bronchiolitis in infants

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    Ana Paula Duarte de Souza

    Full Text Available ABSTRACT Objective: To investigate the correlation between respiratory syncytial viral load and length of hospitalization in infants with acute wheezing episodes. Methods: This was a two-year, cross-sectional study of infants ≤ 12 months of age with bronchiolitis at the time of admission to a tertiary hospital. For the identification of respiratory viruses, nasopharyngeal secretions were collected. Samples were analyzed (throughout the study period by direct immunofluorescence and (in the second year of the study by quantitative real-time PCR. We screened for three human viruses: rhinovirus, respiratory syncytial virus, and metapneumovirus. Results: Of 110 samples evaluated by direct immunofluorescence, 56 (50.9% were positive for a single virus, and 16 (14.5% were positive for two or more viruses. Among those 72 samples, the most prevalent virus was respiratory syncytial virus, followed by influenza. Of 56 samples evaluated by quantitative real-time PCR, 24 (42.8% were positive for a single virus, and 1 (1.7% was positive for two viruses. Among those 25 samples, the most prevalent virus was again respiratory syncytial virus, followed by human rhinovirus. Coinfection did not influence the length of the hospital stay or other outcome s. In addition, there was no association between respiratory syncytial virus load and the length of hospitalization. Conclusions: Neither coinfection nor respiratory syncytial viral load appears to influence the outcomes of acute bronchiolitis in infants.

  2. Lack of association between viral load and severity of acute bronchiolitis in infants

    Science.gov (United States)

    de Souza, Ana Paula Duarte; Leitão, Lidiane Alves de Azeredo; Luisi, Fernanda; Souza, Rodrigo Godinho; Coutinho, Sandra Eugênia; da Silva, Jaqueline Ramos; Mattiello, Rita; Pitrez, Paulo Márcio Condessa; Stein, Renato Tetelbom; Pinto, Leonardo Araújo

    2016-01-01

    ABSTRACT Objective: To investigate the correlation between respiratory syncytial viral load and length of hospitalization in infants with acute wheezing episodes. Methods: This was a two-year, cross-sectional study of infants ≤ 12 months of age with bronchiolitis at the time of admission to a tertiary hospital. For the identification of respiratory viruses, nasopharyngeal secretions were collected. Samples were analyzed (throughout the study period) by direct immunofluorescence and (in the second year of the study) by quantitative real-time PCR. We screened for three human viruses: rhinovirus, respiratory syncytial virus, and metapneumovirus. Results: Of 110 samples evaluated by direct immunofluorescence, 56 (50.9%) were positive for a single virus, and 16 (14.5%) were positive for two or more viruses. Among those 72 samples, the most prevalent virus was respiratory syncytial virus, followed by influenza. Of 56 samples evaluated by quantitative real-time PCR, 24 (42.8%) were positive for a single virus, and 1 (1.7%) was positive for two viruses. Among those 25 samples, the most prevalent virus was again respiratory syncytial virus, followed by human rhinovirus. Coinfection did not influence the length of the hospital stay or other outcome s. In addition, there was no association between respiratory syncytial virus load and the length of hospitalization. Conclusions: Neither coinfection nor respiratory syncytial viral load appears to influence the outcomes of acute bronchiolitis in infants. PMID:27832233

  3. Absence of Siglec-H in MCMV infection elevates interferon alpha production but does not enhance viral clearance.

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    Franz Puttur

    Full Text Available Plasmacytoid dendritic cells (pDCs express the I-type lectin receptor Siglec-H and produce interferon α (IFNα, a critical anti-viral cytokine during the acute phase of murine cytomegalovirus (MCMV infection. The ligands and biological functions of Siglec-H still remain incompletely defined in vivo. Thus, we generated a novel bacterial artificial chromosome (BAC-transgenic "pDCre" mouse which expresses Cre recombinase under the control of the Siglec-H promoter. By crossing these mice with a Rosa26 reporter strain, a representative fraction of Siglec-H⁺ pDCs is terminally labeled with red fluorescent protein (RFP. Interestingly, systemic MCMV infection of these mice causes the downregulation of Siglec-H surface expression. This decline occurs in a TLR9- and MyD88-dependent manner. To elucidate the functional role of Siglec-H during MCMV infection, we utilized a novel Siglec-H deficient mouse strain. In the absence of Siglec-H, the low infection rate of pDCs with MCMV remained unchanged, and pDC activation was still intact. Strikingly, Siglec-H deficiency induced a significant increase in serum IFNα levels following systemic MCMV infection. Although Siglec-H modulates anti-viral IFNα production, the control of viral replication was unchanged in vivo. The novel mouse models will be valuable to shed further light on pDC biology in future studies.

  4. Natural killer KIR3DS1 is closely associated with HCV viral clearance and sustained virological response in HIV/HCV patients.

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    Antonio Rivero-Juarez

    Full Text Available AIM: To evaluate the influence of the presence of the killer cell immunoglobulin-like receptor (KIR 3DS1 on HCV treatment response in HIV/HCV genotype 1 co-infected patients. METHODS: HIV/HCV co-infected patients were included. KIR3DS1, their specific HLA-B ligands and IL28B gene were genotyped. Reductions of plasma HCV RNA levels between baseline and week 1, week 2 and week 4 were analyzed for IL28B genotype and KIR3DS1 (HLA Bw4 or Bw6. Rapid and sustained virological response (RVR and SVR rates were also analyzed. RESULTS: Sixty HIV/HCV genotype 1 co-infected patients were included. Patients with KIR3DS1 and Bw4 had higher rates of HCV viral decline than those who were not carriers of KIR3DS1 (week 1: p = 0.01; week 2: p = 0.038; week 4: p = 0.03. Patients carrying KIR3DS1/Bw4 had higher rates of RVR and SVR than those who did not carry KIR3DS1 (RVR: 46.15% versus 17.02%, p = 0.012; SVR: 63.6% versus 13 26.5%, p = 0.031. With respect to patients carrying the IL28B-CC genotype, those with KIR3DS1/Bw4 had greater rates of HCV viral clearance (week 1: p<0.001; week 2: p = 0.01; week 4: p = 0.02, RVR (p = 0.015 and SVR (p = 0.029 than those not carrying KIR3DS1. CONCLUSION: Our results show that the KIR3DS1 genotype has a positive effect on HCV viral clearance during the first weeks of Peg-IFN/RBV treatment in HCV/HCV co-infected patients bearing genotype 1, and higher RVR and SVR rates.

  5. ADVANCED LIVER INJURY IN PATIENTS WITH CHRONIC HEPATITIS B AND VIRAL LOAD BELOW 2,000 IU/mL

    Science.gov (United States)

    de OLIVEIRA, Valter Oberdan Borges; OLIVEIRA, Juliana Passos Rocha; de FRANÇA, Eloy Vianey Carvalho; BRITO, Hugo Leite de Farias; NASCIMENTO, Tereza Virgínia; FRANÇA, Alex

    2016-01-01

    SUMMARY Introduction: According to the guidelines, the viral load of 2,000 IU/mL is considered the level to differentiate between inactive carriers and HBeAg(-) chronic hepatitis B patients. Even so, liver damage may be present in patients with lower viral load levels, mainly related to regional variations. This study aims to verify the presence of liver injury in patients with viral load below 2,000 IU/mL. Methods: Patients presenting HBsAg(+) for more than six months, Anti-HBe(+)/HBeAg(-), viral load below 2,000 IU/mL and serum ALT levels less than twice the upper limit of normality underwent liver biopsy. Clinical and laboratory characteristics were evaluated in relation to the degree of histologic alteration. Liver injury was considered advanced when F ≥ 2 and/or A ≥ 2 by the METAVIR classification. Results: 11/27 (40.7%) patients had advanced liver injury, with a mean viral load of 701.0 (± 653.7) IU/mL versus 482.8 (± 580.0) IU/mL in patients with mild injury. The comparison between the mean values of the two groups did not find a statistical difference (p = 0.37). The average of serum aminotransferases was not able to differentiate light liver injury from advanced injury. Conclusions: In this study, one evaluation of viral load did not exclude the presence of advanced liver damage. Pathologic assessment is an important tool to diagnose advanced liver damage and should be performed in patients with a low viral load to indicate early antiviral treatment. PMID:27680170

  6. ADVANCED LIVER INJURY IN PATIENTS WITH CHRONIC HEPATITIS B AND VIRAL LOAD BELOW 2,000 IU/mL

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    Valter Oberdan Borges de OLIVEIRA

    Full Text Available SUMMARY Introduction: According to the guidelines, the viral load of 2,000 IU/mL is considered the level to differentiate between inactive carriers and HBeAg(- chronic hepatitis B patients. Even so, liver damage may be present in patients with lower viral load levels, mainly related to regional variations. This study aims to verify the presence of liver injury in patients with viral load below 2,000 IU/mL. Methods: Patients presenting HBsAg(+ for more than six months, Anti-HBe(+/HBeAg(-, viral load below 2,000 IU/mL and serum ALT levels less than twice the upper limit of normality underwent liver biopsy. Clinical and laboratory characteristics were evaluated in relation to the degree of histologic alteration. Liver injury was considered advanced when F ≥ 2 and/or A ≥ 2 by the METAVIR classification. Results: 11/27 (40.7% patients had advanced liver injury, with a mean viral load of 701.0 (± 653.7 IU/mL versus 482.8 (± 580.0 IU/mL in patients with mild injury. The comparison between the mean values of the two groups did not find a statistical difference (p = 0.37. The average of serum aminotransferases was not able to differentiate light liver injury from advanced injury. Conclusions: In this study, one evaluation of viral load did not exclude the presence of advanced liver damage. Pathologic assessment is an important tool to diagnose advanced liver damage and should be performed in patients with a low viral load to indicate early antiviral treatment.

  7. Oral mucosal lesions and HIV viral load in the Women's Interagency HIV Study (WIHS).

    Science.gov (United States)

    Greenspan, D; Komaroff, E; Redford, M; Phelan, J A; Navazesh, M; Alves, M E; Kamrath, H; Mulligan, R; Barr, C E; Greenspan, J S

    2000-09-01

    The prevalence of oral lesions was assessed in a five-center subset of the Women's Interagency HIV Study (WIHS) and correlated with other features of HIV disease. Oral examinations were performed by dental examiners on 729 women (577 HIV-positive and 152 HIV-negative) during baseline examination. Significant differences between the groups were found for the following oral lesions: pseudomembranous candidiasis, 6.1% and 2.0%, respectively; erythematous candidiasis, 6.41% and 0.7%, respectively; all oral candidiasis, pseudomembranous and/or erythematous, 13.7% and 3.3%, respectively. Hairy leukoplakia was observed in 6.1% of HIV-positive women. No significant differences were found for recurrent aphthous ulcers, herpes simplex lesions, or papillomas. Kaposi's sarcoma was seen in 0.5% of HIV-positive and 0% of HIV-negative women. Using multiple logistic regression models controlling for use of antiretrovirals and antifungals, in HIV-positive women the presence of oral candidiasis was associated with a CD4 count <200 cells/microl, cigarette smoking, and heroin/methadone use; the presence of hairy leukoplakia was not related to CD4 count but was associated with high viral load. Oral candidiasis and hairy leukoplakia are confirmed as being common features of HIV infection in women and appear to be associated with HIV viral load, immunosuppression, and various other behaviorally determined variables.

  8. Association of genotypes with viral load and biochemical markers in HCV-infected Sindhi patients

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    Saba Riaz

    Full Text Available Abstract The presented study had two objectives. The first was to examine distributions of Hepatitis C Virus (HCV genotypes in Sindh, Pakistan, where HCV is prevalent. The other was to explore clinically relevant relationships between the genotypes, viral load (measured by real-time polymerase chain reaction assays and biochemical markers. For this, 1471 HCV-infected patients in six cities in Sindh were recruited and sampled. HCV genotype distributions varied among the cities, but genotype 3a was most prevalent, followed by 3b, 1a and 1b (detected in 51.5, 22.7. 9.25 and 3.2% of the cases, respectively. No type-specific sequences were detected in serum samples from 189 (12.8% of the 1471 patients. Frequencies of low (600,000 IU/mL serum viral loads were respectively 45.4, 16.5 and 38.1% for patients infected with genotype 3, and 16.9, 36.9 and 46.2%, respectively, for patients with other genotypes. Infection with genotype 1a was associated with significantly higher (p < 0.005 alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase titers than infection with genotype 3a. The results will help in the formulation of treatment strategies.

  9. Positive Correlation between Epstein-Barr Virus Viral Load and Anti-Viral Capsid Immunoglobulin G Titers Determined for Hodgkin's Lymphoma Patients and Their Relatives

    OpenAIRE

    Besson, Caroline; Amiel, Corinne; Le-Pendeven, Catherine; Brice, Pauline; Fermé, Christophe; Carde, Patrice; Hermine, Olivier; Raphael, Martine; Abel, Laurent; Nicolas, Jean-Claude

    2006-01-01

    Markers of Epstein-Barr virus (EBV) infection include measures of specific serological titers and of viral load (VLo) in peripheral blood mononuclear cells. Few studies have investigated the correlation between these two phenotypes. Here, we found that there was no correlation between VLo and either anti-EBV nuclear antigen type 1 or anti-early antigen immunoglobulin G (IgG) titer but that anti-viral capsid antigen (VCA) IgG titer increased with VLo in peripheral blood mononuclear cells in pa...

  10. CD4 cell count and the risk of AIDS or death in HIV-Infected adults on combination antiretroviral therapy with a suppressed viral load

    DEFF Research Database (Denmark)

    Obel, Niels

    2012-01-01

    Most adults infected with HIV achieve viral suppression within a year of starting combination antiretroviral therapy (cART). It is important to understand the risk of AIDS events or death for patients with a suppressed viral load.......Most adults infected with HIV achieve viral suppression within a year of starting combination antiretroviral therapy (cART). It is important to understand the risk of AIDS events or death for patients with a suppressed viral load....

  11. Persistence of Hepatitis C RNA in Liver Allografts Is Associated with Histologic Progression Independent of Serologic Viral Clearance

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    M. Ghabril

    2009-01-01

    Full Text Available Background. Hepatitis C virus (HCV nondetectability in the liver may predict a sustained viral response (SVR in patients with an end of treatment response. HCV RNA can be detected in liver tissue by in situ hybridization (ISH. Aim. To determine if HCV nondetectability in liver allografts by ISH can predict SVR in patients who cleared virus serologically on treatment. Methods. Twenty five patients with undetectable serum HCV on Interferon/Ribavirin therapy for HCV recurrence post liver transplant (LT were studied. All had biopsies at 4 months post LT (baseline and follow up with HCV ISH analysis performed. Results. 10 were ISH positive (group 1; 15 were ISH negative (group 2. Groups 1 and 2 had similar patient, donor, and viral characteristics at LT, as well as treatment duration at the time of the ISH assayed liver biopsy (13±16 versus 10±4 months P = .24. However, group 1 had longer total treatment duration (24±10 versus 14±5 months, P = .001. Eight (80% group 1 and 9 (60% group 2 patients achieved SVR. Mean grade and stage (modified Ishak score were similar at 4 months, however, group 1 had higher grade (3±1.7 versus 1.6±1.3, P = .039 and stage (1.4±1.4 versus 0.5±0.6, P = .084 on the ISH assayed biopsy, after similar post LT intervals (23±10 versus 24±12 months, P = .91. Conclusion. Allograft HCV ISH nondetectability does not predict SVR in treatment responsive HCV recurrence, but is associated with less severe histologic disease.

  12. Mutagenesis-mediated virus extinction: Virus-dependent effect of viral load on sensitivity to lethal defection

    OpenAIRE

    Héctor Moreno; Héctor Tejero; Juan Carlos de la Torre; Esteban Domingo; Verónica Martín

    2012-01-01

    Background: Lethal mutagenesis is a transition towards virus extinction mediated by enhanced mutation rates during viral genome replication, and it is currently under investigation as a potential new antiviral strategy. Viral load and virus fitness are known to influence virus extinction. Here we examine the effect or the multiplicity of infection (MOI) on progeny production of several RNA viruses under enhanced mutagenesis. Results: The effect of the mutagenic base analogue 5-fluorouracil (F...

  13. Impact of two different commercial DNA extraction methods on BK virus viral load

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    Massimiliano Bergallo

    2016-03-01

    Full Text Available Background and aim: BK virus, a member of human polyomavirus family, is a worldwide distributed virus characterized by a seroprevalence rate of 70-90% in adult population. Monitoring of viral replication is made by evaluation of BK DNA by quantitative polymerase chain reaction. Many different methods can be applied for extraction of nucleic acid from several specimens. The aim of this study was to assess the impact of two different DNA extraction procedure on BK viral load. Materials and methods: DNA extraction procedure including the Nuclisens easyMAG platform (bioMerieux, Marcy l’Etoile, France and manual QIAGEN extraction (QIAGEN Hilden, Germany. BK DNA quantification was performed by Real Time TaqMan PCR using a commercial kit. Result and discussion: The samples capacity, cost and time spent were compared for both systems. In conclusion our results demonstrate that automated nucleic acid extraction method using Nuclisense easyMAG was superior to manual protocol (QIAGEN Blood Mini kit, for the extraction of BK virus from serum and urine specimens.

  14. ASSASYING THE NEED OF COMMERCIAL PLASMA VIRAL LOAD TESTING IN RESOURCE LIMITED SETTINGS

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    Arnaw

    2015-09-01

    Full Text Available Around nine million Human Immunodeficiency Virus (HIV infected individuals are on antiretroviral therapy (ART. People living with HIV/AIDS in resource - limited settings where HIV burden is usually high, there is an urgent need of affordable, accessible and inexpensive tests to monitor response to treatment. Quite a few commercially available assay has been introduced to measure Plasma Viral Load (PVL as testing can increase adherence to ART and facilitate timely switching of failing regimens and thus minimizing the development of resistance. We analyzed Nucleic Acid Test (NAT based assay and Non Nucleic Acid Test based assay for PVL testing. Though both the assay has its own advantage and disadvantages, but the use of Non Nucleic Acid Test has an upper hand in resource limited settings. It is the duty of administration, clinicians, microbiologist and health care personnel to introduce appropriate laboratory monitoring assays in resource - limited settings.

  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. Point-of-Care Viral Load Testing for Sub-Saharan Africa: Informing a Target Product Profile

    Science.gov (United States)

    Phillips, Andrew N.; Cambiano, Valentina; Nakagawa, Fumiyo; Ford, Deborah; Apollo, Tsitsi; Murungu, Joseph; Rousseau, Christine; Garnett, Geoff; Ehrenkranz, Peter; Bansi-Matharu, Loveleen; Vojnov, Lara; Katz, Zachary; Peeling, Rosanna; Revill, Paul

    2016-01-01

    Point-of-care viral load tests are being developed to monitor patients on antiretroviral therapy (ART) in sub-Saharan Africa. Test design involves trade-offs between test attributes, including accuracy, complexity, robustness, and cost. We used a model of the human immunodeficiency virus epidemic and ART program in Zimbabwe and found that the attributes of a viral load testing approach that are most influential for cost effectiveness are avoidance of a high proportion of failed tests or results not received, use of an approach that best facilitates retention on ART, and the ability to facilitate greater use of differentiated care, including through expanding coverage of testing availability. PMID:27704016

  17. Blood micronutrient, oxidative stress, and viral load in patients with chronic hepatitis C

    Institute of Scientific and Technical Information of China (English)

    Wang-Sheng Ko; Chih-Hung Guo; Maw-Sheng Yeh; Li-Yun Lin; Guoo-Shyng W.Hsu; Pei-Chung Chen; Mei-Ching Luo; Chia-Yeh Lin

    2005-01-01

    AIM: To assess the extent of micronutrient and oxidative stress in blood and to examine their linkages with viral loads in chronic hepatitis C patients.METHODS: Hepatitis C virus (HCV)-RNA levels were quantified in the serum from 37 previously untreated patients with chronic hepatitis C. The plasma and erythrocyte micronutrients (zinc, selenium, copper, and iron) were estimated, and malondialdehyde (MDA)contents were determined as a marker to detect oxidative stress. Antioxidant enzymes, superoxide dismutase (SOD),glutathione peroxidase (GPX) and glutathione reductase (GR) activities in blood were also measured. The control group contained 31 healthy volunteers.RESULTS: The contents of zinc (Zn), and selenium (Se)in plasma and erythrocytes were significantly lower in hepatitis C patients than in the controls. On the contrary,copper (Cu) levels were significantly higher. Furthermore,plasma and erythrocyte MDA levels, and the SOD and GR activities in erythrocytes significantly increased in hepatitis C patients compared to the controls. However, the plasma GPX activity in patients was markedly lower. Plasma Se (r= -0.730, P<0.05), Cu (r = 0.635), and GPX (r = -0.675)demonstrated correlations with HCV-RNA loads. Significant correlation coefficients were also observed between HCV-RNA levels and erythrocyte Zn (r = -0.403), Se (r = -0.544), Cu (r = 0.701) and MDA (r = 0.629) and GR (r = 0.441).CONCLUSION: The levels of Zn, Se, Cu, and oxidative stress (MDA), as well as related anti-oxidative enzymes (GR and GPX) in blood have important impact on the viral factors in chronic hepatitis C. The distribution of these parameters might be significant biomarkers for HCV.

  18. EVOLUTION OF HIV-1 VIRAL LOAD IN PATIENTS FOLLOWED-UP FOR OVER 3 YEARS

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    Labayru C

    2006-02-01

    Full Text Available ABSTRACTObjectives: To describe the evolution of a Human Immunodeficiency Virus Type 1 (HIV-1 infected patient cohort monitored for over 1,000 days.Methods: HIV-1 Viral Load (VL, CD4/l lymphocyte values and antiretroviral therapies given to the patients were evaluated throughout the follow-up period. We present a retrospective descriptive study of the HIV-1 VL determinations performed on 369 individuals followed-up for over 1,000 days.Results: The "non-detectable" VL ( 100.000 copies/ml from the interval of 0-75 days up to the interval of 501-1,000 days (t-test, p=0.005; at that point, results switched to the opposite.Conclusions: Both CD4/ cell count lower than 200x106 and patients receiving highly active antiretroviral therapies (HAART were related to "non-detectable" VL levels. In our series the time period between 700 and 1,000 days can be the maximum interval for benefits from therapy and virology evaluation.RESUMENObjetivo: Describir la evolución de una cohorte de pacientes con infección por el Virus de la Inmunodeficiencia Humana (VIH monitorizados durante más 3 años.Métodos: Durante el período de seguimiento se han evaluado en 396 individuos con infección VIH, seguidos durante más de 1000 días los parámetros de carga viral, valores de linfocitos CD4 y terapia antirretroviral.Resultados: Las porcentajes de carga viral no detectable (100.000 copias/ARN/ml, y su rango adquirió significación desde el intervalo de 0-75 días de seguimiento al de 501-100 días (t-test, p=0.005. Los recuentos de CD4 bajos (<200 en pacientes que recibieron Terapia antirretroviral de alta eficacia se asociaron a valores indetectables de carga viral.Conclusiones: En nuestra serie el período situado entre 700-100 días representó el intervalo de máximo beneficio para la evaluación virológica y terapéutica.

  19. Clinical value of determination HIV viral load in the cerebrospinal fluid of HIV-infected patients

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    V. B. Musatov

    2015-01-01

    Full Text Available Aim. To analyze the concentration of HIV RNA in the cerebrospinal fluid and to evaluate its significance in the pathology of the central nervous system among HIV infected persons.Materials: We examined 36 patients with HIV infection with signs of pathology of the central nervous system. All patients was done completed a standard investigation of cerebrospinal fluid, cytological examination and detection viral load of HIV in the cerebrospinal fluid and serum.Results. A different of opportunistic and HIV-related disease was diagnosed in 29 patients. The most frequent pathology of the nervous system (12 cases is a diffuse HIV-associated brain damage occurring in 7 patients in the form of aseptic non purulent meningitis and in 5 patients in the form of encephalitis. The average value of the absolute and relative count of CD4-lymphocytes in patients amounted 147,0 cells/μl (40,0; 408,75 and 10.0% (4,00; 18,50. Pathological changes in cellular composition and protein concentration of cerebrospinal fluid detected in 19 cases. Replication of HIV in the cerebrospinal fluid are detected in 31 of 32 patients not receiving antiretroviral therapy, including 17 patients with normal values of cerebrospinal fluid. The average HIV viral load in the cerebrospinal fluid was 15 133,0 copies/ml (2501,0; 30624,0 or 4,18 (3,35; 4,48 lg HIV RNA, average HIV viral load in serum – 62 784,0 copies/ml (6027,5; 173869,0 or 4,80 4,80 (3,7; 5,2 lg HIV RNA. The concentration of HIV in the cerebrospinal fluid was significantly lower than in serum (4,18 and 4,80 lg HIV RNA, p=0.027. 4 patients with severe, multietiology damage of the central nervous system viral, microbial and fungal etiology, there was an inverse relationship between the concentration of HIV in the cerebrospinal fluid and in serum, the concentrations of HIV was higher in the cerebrospinal fluid.Conclusion: Among the majority of HIV-infected patients with signs of the central

  20. TTV viral load as a marker for immune reconstitution after initiation of HAART in HIV-infected patients

    DEFF Research Database (Denmark)

    Madsen, Chris; Eugen-Olsen, Jesper; Kirk, Ole;

    2002-01-01

    PURPOSE: To investigate whether TT virus (TTV) viral load may be used as a surrogate marker for functional immune reconstitution in HIV-infected patients receiving highly active antiretroviral therapy (HAART). METHOD: Fifteen protease inhibitor-naïve HIV-infected patients were included in a longi......PURPOSE: To investigate whether TT virus (TTV) viral load may be used as a surrogate marker for functional immune reconstitution in HIV-infected patients receiving highly active antiretroviral therapy (HAART). METHOD: Fifteen protease inhibitor-naïve HIV-infected patients were included...... in a longitudinal study. From each patient, three serum samples taken before HAART initiation and three samples taken during HAART were analyzed. TTV was detected by polymerase chain reaction (PCR) and was quantitated by competitive PCR. TTV viral heterogeneity was determined by restriction fragment length...

  1. Undetectable plasma viral load predicts normal survival in HIV-2-infected people in a West African village

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    Ricard Dominique

    2010-05-01

    Full Text Available Abstract Background There have been no previous studies of the long-term survival and temporal changes in plasma viral load among HIV-2 infected subjects. Methods 133 HIV-2 infected and 158 HIV-uninfected subjects from a rural area in North-west Guinea-Bissau, West Africa were enrolled into a prospective cohort study in 1991 and followed-up to mid-2009. Data were collected on four occasions during that period on HIV antibodies, CD4% and HIV-2 plasma viral load. Results Median age (interquartile range [IQR] of HIV-2 infected subjects at time of enrollment was 47 (36, 60 years, similar to that of HIV-uninfected control subjects, 49 (38, 62 (p = 0.4. Median (IQR plasma viral load and CD4 percentage were 347 (50, 4,300 copies/ml and 29 (22, 35 respectively. Overall loss to follow-up to assess vital status was small, at 6.7% and 6.3% for HIV-2 infected and uninfected subjects respectively. An additional 17 (12.8% and 16 (10.1% of HIV-2 infected and uninfected subjects respectively were censored during follow-up due to infection with HIV-1. The mortality rate per 100 person-years (95% CI was 4.5 (3.6, 5.8 among HIV-2 infected subjects compared to 2.1 (1.6, 2.9 among HIV-uninfected (age-sex adjusted rate ratio 1.9 (1.3, 2.8, p Viral load measurements were available for 98%, 78%, 77% and 61% HIV-2 infected subjects who were alive and had not become super-infected with HIV-1, in 1991, 1996, 2003 and 2006 respectively. Median plasma viral load (RNA copies per ml (IQR did not change significantly over time, being 150 (50, 1,554; n = 77 in 1996, 203 (50, 2,837; n = 47 in 2003 and 171 (50, 497; n = 31 in 2006. Thirty seven percent of HIV-2 subjects had undetectable viraemia ( Conclusions A substantial proportion of HIV-2 infected subjects in this cohort have stable plasma viral load, and those with an undetectable viral load (37% at study entry had a normal survival rate. However, the sequential laboratory findings need to be interpreted with caution given

  2. Beak and feather disease virus: correlation between viral load and clinical signs in wild Cape parrots (Poicepahlus robustus) in South Africa.

    Science.gov (United States)

    Regnard, Guy L; Boyes, Rutledge S; Martin, Rowan O; Hitzeroth, Inga I; Rybicki, Edward P

    2015-01-01

    Psittacine beak and feather disease (PBFD), the most prevalent viral disease affecting psittacines, is caused by beak and feather disease virus (BFDV). This study assessed viral load using qPCR in a wild Cape parrot population affected by PBFD and compared it to overall physical condition based on clinical signs attributable to PBFD. A significant inverse correlation between viral load and overall physical condition was found, which confirmed that clinical signs may confidently be used to diagnose the relative severity of BFDV infections in wild populations. This is the first assessment of BFDV viral load in a wild psittacine population.

  3. PROSPECTIVE STUDY OF HPV16 VIRAL LOAD AND RISK OF IN SITU AND INVASIVE SQUAMOUS CERVICAL CANCER

    Science.gov (United States)

    Sundström, Karin; Ploner, Alexander; Dahlström, Lisen Arnheim; Palmgren, Juni; Dillner, Joakim; Adami, Hans-Olov; Ylitalo, Nathalie; Sparén, Pär

    2012-01-01

    Background A strong association has been shown between high viral DNA load (VL) of human papillomavirus (HPV) type 16 and risk for cervical cancer in situ (CIS). However, little data is available for the significance of VL in invasive squamous cell carcinoma (SCC). Methods In two nested case-control studies among women participating in cervical screening, with a cytologically normal first smear, we collected 5665 smears from 621 women with CIS, 457 with SCC, and individually matched controls. All smears were tested for HPV, and VLs of HPV16 positive smears were quantified using realtime-PCR. The median follow-up until diagnosis of CIS or SCC was 6.1-7.7 years. Results Low VL’s were common among both CIS and SCC case women, until 1-2 years before diagnosis when a surge in VL occurred. The relative risk (RR) associated with low viral load of HPV16 was around 10 for CIS, and 10-20 for SCC throughout 10 years before diagnosis, compared to HPV16-negative women. For women with medium to high VL, the risk for CIS was greatly increased from five years before diagnosis (RR=19, 95% confidence interval 7-48). In SCC, a high VL conferred an increased risk, but only from 3 years before diagnosis (RR=60, 95% CI 6-580). Conclusions We demonstrate differing risk functions associated with HPV16 viral load in CIS and SCC, respectively. We further show that viral loads were unexpectedly low early in the SCC disease process. Impact HPV16 viral load appears highly complex which may limit its use in cervical screening. PMID:23155137

  4. Dual Function of Ccr5 during Langat Virus Encephalitis: Reduction in Neutrophil-Mediated Central Nervous System Inflammation and Increase in T Cell-Mediated Viral Clearance.

    Science.gov (United States)

    Michlmayr, Daniela; Bardina, Susana V; Rodriguez, Carlos A; Pletnev, Alexander G; Lim, Jean K

    2016-06-01

    Tick-borne encephalitis virus (TBEV) is a vector-transmitted flavivirus that causes potentially fatal neurologic infection. There are thousands of cases reported annually, and despite the availability of an effective vaccine, the incidence of TBEV is increasing worldwide. Importantly, up to 30% of affected individuals develop long-term neurologic sequelae. We investigated the role of chemokine receptor Ccr5 in a mouse model of TBEV infection using the naturally attenuated tick-borne flavivirus Langat virus (LGTV). Ccr5-deficient mice presented with an increase in viral replication within the CNS and decreased survival during LGTV encephalitis compared with wild-type controls. This enhanced susceptibility was due to the temporal lag in lymphocyte migration into the CNS. Adoptive transfer of wild-type T cells, but not Ccr5-deficient T cells, significantly improved survival outcome in LGTV-infected Ccr5-deficient mice. Concomitantly, a significant increase in neutrophil migration into the CNS in LGTV-infected Ccr5(-/-) mice was documented at the late stage of infection. Ab-mediated depletion of neutrophils in Ccr5(-/-) mice resulted in a significant improvement in mortality, a decrease in viral load, and a decrease in overall tissue damage in the CNS compared with isotype control-treated mice. Ccr5 is crucial in directing T cells toward the LGTV-infected brain, as well as in suppressing neutrophil-mediated inflammation within the CNS.

  5. Positive Correlation between Epstein-Barr Virus Viral Load and Anti-Viral Capsid Immunoglobulin G Titers Determined for Hodgkin's Lymphoma Patients and Their Relatives

    Science.gov (United States)

    Besson, Caroline; Amiel, Corinne; Le-Pendeven, Catherine; Brice, Pauline; Fermé, Christophe; Carde, Patrice; Hermine, Olivier; Raphael, Martine; Abel, Laurent; Nicolas, Jean-Claude

    2006-01-01

    Markers of Epstein-Barr virus (EBV) infection include measures of specific serological titers and of viral load (VLo) in peripheral blood mononuclear cells. Few studies have investigated the correlation between these two phenotypes. Here, we found that there was no correlation between VLo and either anti-EBV nuclear antigen type 1 or anti-early antigen immunoglobulin G (IgG) titer but that anti-viral capsid antigen (VCA) IgG titer increased with VLo in peripheral blood mononuclear cells in patients with Hodgkin's lymphoma (P = 3.10−3). A similar pattern was observed in healthy first-degree relatives (parents and siblings) of patients (P = 6.10−4). Our results indicate that anti-VCA IgG titers and EBV VLo are specifically correlated EBV phenotypes. PMID:16390946

  6. Attenuated SIV causes persisting neuroinflammation in the absence of a chronic viral load and neurotoxic antiretroviral therapy

    Science.gov (United States)

    Ferguson, Deborah; Clarke, Sean; Berry, Neil; Almond, Neil

    2016-01-01

    Objectives: Using simian models, where SIV chronic viral loads are naturally controlled in the absence of potentially neurotoxic therapies, we investigated the neuropathological events occurring during times of suppressed viraemia and when these events were initiated. Design: Cynomolgus macaques were infected with SIV strains that are naturally controlled to low levels of chronic viraemia. Study 1: animals were maintained up to 300 days after inoculation and analysed for viral-induced neuropathology following sustained suppression of chronic viral loads. Study 2: initiation and development of lesion was examined following 3, 10, 21, or 125 days SIVmacC8 infection. Methods: Formalin-fixed, paraffin-embedded brain sections were analysed following immunohistochemical staining for simian immunodeficiency virus (SIV) (KK41), blood–brain barrier leakage (ZO-1, fibrinogen), apoptosis (active caspase 3), neuroinflammation [GFAP, cyclooxygenase (COX)-1, COX-2], microglia and macrophage (Iba-1, CD68, and CD16), oligodendrocytes (CNPase1), MHC class II expression, and T cells (CD3 and CD8). Replicating SIV was detected through in-situ hybridization. Results: Study 1: neuroinflammation was present despite prolonged suppressed viraemia. Study 2: attenuated SIV entered the brain rapidly triggering acute phase neuroinflammatory responses. These did not return to naive levels and GFAP and COX-2 responses continued to develop during a chronic phase with a suppressed viral load. Conclusion: Neuroinflammatory responses similar to those in HIV neurocognitively impaired patients are present within macaque brains during prolonged periods of suppressed SIV viral load and in the absence of potentially neurotoxic antiretroviral drugs. These responses, initiated during acute infection, do not resolve despite the lack of on-going peripheral viraemia to potentially reseed the brain. PMID:27258396

  7. Using Exclusion-Based Sample Preparation (ESP) to Reduce Viral Load Assay Cost.

    Science.gov (United States)

    Berry, Scott M; Pezzi, Hannah M; Williams, Eram D; Loeb, Jennifer M; Guckenberger, David J; Lavanway, Alex J; Puchalski, Alice A; Kityo, Cissy M; Mugyenyi, Peter N; Graziano, Franklin M; Beebe, David J

    2015-01-01

    Viral load (VL) measurements are critical to the proper management of HIV in developing countries. However, access to VL assays is limited by the high cost and complexity of existing assays. While there is a need for low cost VL assays, performance must not be compromised. Thus, new assays must be validated on metrics of limit of detection (LOD), accuracy, and dynamic range. Patient plasma samples from the Joint Clinical Research Centre in Uganda were de-identified and measured using both an existing VL assay (Abbott RealTime HIV-1) and our assay, which combines low cost reagents with a simplified method of RNA isolation termed Exclusion-Based Sample Preparation (ESP).71 patient samples with VLs ranging from 3,000,000 copies/mL were used to compare the two methods. We demonstrated equivalent LOD (~50 copies/mL) and high accuracy (average difference between methods of 0.08 log, R2 = 0.97). Using expenditures from this trial, we estimate that the cost of the reagents and consumables for this assay to be approximately $5 USD. As cost is a significant barrier to implementation of VL testing, we anticipate that our assay will enhance access to this critical monitoring test in developing countries.

  8. Global cost modeling analysis of HIV-1 and HCV viral load assays.

    Science.gov (United States)

    Elbeik, Tarek; Chen, Yi-Ming Arthur; Soutchkov, Serguei V; Loftus, Richard A; Beringer, Scott

    2003-08-01

    This review addresses hidden costs associated with the Bayer VERSANT assay, Roche AMPLICOR MONITOR test and COBAS AMPLICOR MONITOR test and how these influence the final per reportable cost to a testing laboratory in resource-rich and -poor countries. An in-depth evaluation and recommendation of the most cost-effective approach for these tests is presented. The analyses demonstrate the need for manufacturers to consider labor and supply costs when marketing a kit in resource-poor countries, noting that marketing strategies need to change. In the absence of any proven monitoring alternative, emphasis is placed on increasing market share to promote significant reduction in kit prices to suit the demands of markets in resource-poor countries. Finally, recommendations are made to improve the overall cost structure of viral load testing. This review is intended as a tool to optimize assay usage in attaining the lowest performance costs by assay and is not to endorse any test, as will become apparent.

  9. Using Exclusion-Based Sample Preparation (ESP to Reduce Viral Load Assay Cost.

    Directory of Open Access Journals (Sweden)

    Scott M Berry

    Full Text Available Viral load (VL measurements are critical to the proper management of HIV in developing countries. However, access to VL assays is limited by the high cost and complexity of existing assays. While there is a need for low cost VL assays, performance must not be compromised. Thus, new assays must be validated on metrics of limit of detection (LOD, accuracy, and dynamic range. Patient plasma samples from the Joint Clinical Research Centre in Uganda were de-identified and measured using both an existing VL assay (Abbott RealTime HIV-1 and our assay, which combines low cost reagents with a simplified method of RNA isolation termed Exclusion-Based Sample Preparation (ESP.71 patient samples with VLs ranging from 3,000,000 copies/mL were used to compare the two methods. We demonstrated equivalent LOD (~50 copies/mL and high accuracy (average difference between methods of 0.08 log, R2 = 0.97. Using expenditures from this trial, we estimate that the cost of the reagents and consumables for this assay to be approximately $5 USD. As cost is a significant barrier to implementation of VL testing, we anticipate that our assay will enhance access to this critical monitoring test in developing countries.

  10. Residual viraemia in HIV-1-infected patients with plasma viral load

    DEFF Research Database (Denmark)

    Ostrowski, S.R.; Katzenstein, T.L.; Pedersen, Bente Klarlund;

    2008-01-01

    Despite undetectable viral load in conventional assays, probably all human immunodeficiency virus (HIV)-1 infected patients have residual viraemia (RV) detectable by ultra-sensitive assays. To study this issue, this study investigated virologic and immunologic consequences of RV in highly active...... antiretroviral therapy (HAART)-treated HIV-1-infected patients with plasma HIV-1 RNA or=1 episode with TMA-RV whereas 9 patients had undetectable TMA-RV throughout the study-period. Time-points with TMA-RV and PCR-RV were associated with higher circulating sTNFrII (+0.234 ng/ml, P = 0.030) and beta(2......)-microglobulin (+22 nmol/l, P = 0.016) and time-points with PCR-RV were also associated with higher IgA (+0.82 micromol/l, P = 0.035) and CD8-count (+1.18-fold, P = 0.001). Patients with TMA-RV in the study-period had higher HIV-1 RNA pre-HAART (P = 0.032). RV was not associated with proviral-HIV-1-DNA, CD4...

  11. Dolutegravir treatment response by baseline viral load and NRTI backbone in treatment-naïve HIV-infected individuals

    Directory of Open Access Journals (Sweden)

    C Small

    2012-11-01

    Full Text Available Background: In two 48-week studies in naïve subjects, dolutegravir with NRTI of choice has shown non-inferiority to raltegravir and, with ABC/3TC, superiority to Atripla. Factors that influenced choice of NRTIs included viral load, resistance and safety. Methods: We analysed response rates and time to virologic failure by NRTI backbone and baseline viral load in the pivotal DTG-naïve studies. SPRING-2 randomized participants to DTG 50 mg QD or RAL 400 mg BID, each in combination with investigator-selected NRTIs (TDF/FTC or ABC/3TC. SINGLE randomised participants to DTG 50 mg+ABC/3TC QD or TDF/FTC/EFV (Atripla QD. In SPRING-2, changes in serum creatinine were examined by INI and NRTI backbone. Results: The two studies randomized and treated 1655 subjects, of whom 249 (15% were female, 388 (23% non-white, 495 (30% had HIV-1 RNA >100,000 c/ml, and 224 (14% had CD4+ count <200 cells/mm3. Primary analyses demonstrated non-inferiority of DTG to RAL in SPRING-2 (Δ=2.5%; 95% CI:−2.2% to +7.1%, excluding −10%, and superiority of the DTG regimen in SINGLE (7.4%; +2.5% to +12.3%. In SPRING-2, response rates by NRTI backbone were comparable in each viral load stratum. In SINGLE, a 7% difference in response (favoring DTG+ABC/3TC was observed in each viral load stratum. Exploratory analyses examining time-to-virologic failure showed no difference in response rates between the NRTIs irrespective of baseline viral load or study. Resistance to INIs or NRTIs was not demonstrated in any subject on DTG-based therapy through 48 weeks. Withdrawals due to AEs on DTG-based regimen were few (2% in both studies. In SPRING-2, no significant differences were observed in serum creatinine change from baseline to Week 48 by NRTI backbones. Conclusions: In SPRING-2 and SINGLE, DTG was effective with both ABC/3TC and TDF/FTC, and in subjects with high and low viral load. DTG was well tolerated in both studies. Renal safety also was similar by NRTI backbone. DTG is a once

  12. Morphine increases hippocampal viral load and suppresses frontal lobe CCL5 expression in the LP-BM5 AIDS model.

    Science.gov (United States)

    McLane, Virginia D; Cao, Ling; Willis, Colin L

    2014-04-15

    Chronic opiate abuse accelerates the development of cognitive deficits in human immunodeficiency virus (HIV)-1 patients. To investigate morphine's effects on viral infection of the central nervous system, we applied chronic morphine treatment to the LP-BM5 murine acquired immunodeficiency syndrome (MAIDS) model. LP-BM5 infection induces proinflammatory cytokine/chemokine production, correlating to increased blood-brain barrier permeability. Morphine treatment significantly increased LP-BM5 viral load in the hippocampus, but not in the frontal lobe. Morphine reduced the chemokine CCL5 to non-infected levels in the frontal lobe, but not in the hippocampus. These data indicate a region-specific mechanism for morphine's effects on virally-induced neurocognitive deficits.

  13. Prevalence of Oral Manifestations and Their Association with CD4/CD8 Ratio and HIV Viral Load in South India

    Directory of Open Access Journals (Sweden)

    Sharma Gaurav

    2011-01-01

    Full Text Available The objective of the present research was to determine the prevalence of oral manifestations in an HIV infected population from south India and evaluate their association with HIV viral load and CD4/CD8 ratio. Intraoral examination of 103 patients, whose CD4/CD8 ratio was available, were conducted. HIV viral loads were available for thirty patients only. The prevalence of oral manifestations was 80.6% (83/103. The most common oromucosal lesion was erythematous candidiasis (EC (38.8% followed by melanotic hyperpigmentation (35.9%. Patients having any oral manifestation had a mean CD4/CD8 ratio of 0.24. EC had positive predictive value of 85.0% for CD4/CD8 ratio 20,000 copies/mL (20,000 copies/mL.

  14. Kinetics of viral loads and genotypic analysis of elephant endotheliotropic herpesvirus-1 infection in captive Asian elephants (Elephas maximus).

    Science.gov (United States)

    Stanton, Jeffrey J; Zong, Jian-Chao; Eng, Crystal; Howard, Lauren; Flanagan, Joe; Stevens, Martina; Schmitt, Dennis; Wiedner, Ellen; Graham, Danielle; Junge, Randall E; Weber, Martha A; Fischer, Martha; Mejia, Alicia; Tan, Jie; Latimer, Erin; Herron, Alan; Hayward, Gary S; Ling, Paul D

    2013-03-01

    Elephant endotheliotropic herpesviruses (EEHVs) can cause fatal hemorrhagic disease in juvenile Asian elephants (Elphas maximus); however, sporadic shedding of virus in trunk washes collected from healthy elephants also has been detected. Data regarding the relationship of viral loads in blood compared with trunk washes are lacking, and questions about whether elephants can undergo multiple infections with EEHVs have not been addressed previously. Real-time quantitative polymerase chain reaction was used to determine the kinetics of EEHV1 loads, and genotypic analysis was performed on EEHV1 DNA detected in various fluid samples obtained from five Asian elephants that survived detectable EEHV1 DNAemia on at least two separate occasions. In three elephants displaying clinical signs of illness, preclinical EEHV1 DNAemia was detectable, and peak whole-blood viral loads occurred 3-8 days after the onset of clinical signs. In two elephants with EEHV1 DNAemia that persisted for 7-21 days, no clinical signs of illness were observed. Detection of EEHV1 DNA in trunk washes peaked approximately 21 days after DNAemia, and viral genotypes detected during DNAemia matched those detected in subsequent trunk washes from the same elephant. In each of the five elephants, two distinct EEHV1 genotypes were identified in whole blood and trunk washes at different time points. In each case, these genotypes represented both an EEHV1A and an EEHV1B subtype. These data suggest that knowledge of viral loads could be useful for the management of elephants before or during clinical illness. Furthermore, sequential infection with both EEHV1 subtypes occurs in Asian elephants, suggesting that they do not elicit cross-protective sterilizing immunity. These data will be useful to individuals involved in the husbandry and clinical care of Asian elephants.

  15. Hepatitis B viral load in dried blood spots: a validation study in Zambia

    Science.gov (United States)

    Vinikoor, Michael J.; Zürcher, Samuel; Musukuma, Kalo; Kachuwaire, Obert; Rauch, Andri; Chi, Benjamin H.; Gorgievski, Meri; Zwahlen, Marcel; Wandeler, Gilles

    2016-01-01

    Background Access to hepatitis B viral load (VL) testing is poor in sub-Saharan Africa (SSA) due to economic and logistical reasons. Objectives To demonstrate the feasibility of testing dried blood spots (DBS) for hepatitis B virus (HBV) VL in a laboratory in Lusaka, Zambia, and to compare HBV VLs between DBS and plasma samples. Study design Paired plasma and DBS samples from HIV-HBV co-infected Zambian adults were analyzed for HBV VL using the COBAS AmpliPrep/COBAS TaqMan HBV test (Version 2.0) and for genotype by direct sequencing. We used Bland-Altman analysis to compare VLs between sample types and by HBV genotype. Logistic regression analysis was conducted to assess the probability of an undetectable DBS result by plasma VL. Results Among 68 participants, median age was 34 years, 61.8% were men, and median plasma HBV VL was 3.98 log IU/ml (interquartile range, 2.04–5.95). Among sequenced viruses, 28 were genotype A1 and 27 were genotype E. Bland-Altman plots suggested strong agreement between DBS and plasma VLs. DBS VLs were on average 1.59 log IU/ml lower compared to plasma with 95% limits of agreement of −2.40 to −0.83 log IU/ml. At a plasma VL ≥2,000 IU/ml, the probability of an undetectable DBS result was 1.8% (95% CI: 0.5–6.6). At plasma VL ≥20,000 IU/ml this probability reduced to 0.2% (95% CI: 0.03–1.7). Conclusions In a Zambian laboratory, we observed strong agreement between DBS and plasma VLs and high sensitivity in DBS at plasma VL ≥2,000 IU/ml. As HBV treatment expands, DBS could increase access to HBV VL testing in SSA settings. PMID:26356987

  16. Systematic Review of the Performance of HIV Viral Load Technologies on Plasma Samples

    Science.gov (United States)

    Sollis, Kimberly A.; Smit, Pieter W.; Fiscus, Susan; Ford, Nathan; Vitoria, Marco; Essajee, Shaffiq; Barnett, David; Cheng, Ben; Crowe, Suzanne M.; Denny, Thomas; Landay, Alan; Stevens, Wendy; Habiyambere, Vincent; Perrins, Jos; Peeling, Rosanna W.

    2014-01-01

    Background Viral load (VL) monitoring is the standard of care in developing country settings for detecting HIV treatment failure. Since 2010 the World Health Organization has recommended a phase-in approach to VL monitoring in resource-limited settings. We conducted a systematic review of the accuracy and precision of HIV VL technologies for treatment monitoring. Methods and Findings A search of Medline and Embase was conducted for studies evaluating the accuracy or reproducibility of commercially available HIV VL assays. 37 studies were included for review including evaluations of the Amplicor Monitor HIV-1 v1.5 (n = 25), Cobas TaqMan v2.0 (n = 11), Abbott RealTime HIV-1 (n = 23), Versant HIV-1 RNA bDNA 3.0 (n = 15), Versant HIV-1 RNA kPCR 1.0 (n = 2), ExaVir Load v3 (n = 2), and NucliSens EasyQ v2.0 (n = 1). All currently available HIV VL assays are of sufficient sensitivity to detect plasma virus levels at a lower detection limit of 1,000 copies/mL. Bias data comparing the Abbott RealTime HIV-1, TaqMan v2.0 to the Amplicor Monitor v1.5 showed a tendency of the Abbott RealTime HIV-1 to under-estimate results while the TaqMan v2.0 overestimated VL counts. Compared to the Amplicor Monitor v1.5, 2–26% and 9–70% of results from the Versant bDNA 3.0 and Abbott RealTime HIV-1 differed by greater than 0.5log10. The average intra and inter-assay variation of the Abbott RealTime HIV-1 were 2.95% (range 2.0–5.1%) and 5.44% (range 1.17–30.00%) across the range of VL counts (2log10–7log10). Conclusions This review found that all currently available HIV VL assays are of sufficient sensitivity to detect plasma VL of 1,000 copies/mL as a threshold to initiate investigations of treatment adherence or possible treatment failure. Sources of variability between VL assays include differences in technology platform, plasma input volume, and ability to detect HIV-1 subtypes. Monitoring of individual patients should be performed on the same

  17. Systematic review of the performance of HIV viral load technologies on plasma samples.

    Directory of Open Access Journals (Sweden)

    Kimberly A Sollis

    Full Text Available BACKGROUND: Viral load (VL monitoring is the standard of care in developing country settings for detecting HIV treatment failure. Since 2010 the World Health Organization has recommended a phase-in approach to VL monitoring in resource-limited settings. We conducted a systematic review of the accuracy and precision of HIV VL technologies for treatment monitoring. METHODS AND FINDINGS: A search of Medline and Embase was conducted for studies evaluating the accuracy or reproducibility of commercially available HIV VL assays. 37 studies were included for review including evaluations of the Amplicor Monitor HIV-1 v1.5 (n = 25, Cobas TaqMan v2.0 (n = 11, Abbott RealTime HIV-1 (n = 23, Versant HIV-1 RNA bDNA 3.0 (n = 15, Versant HIV-1 RNA kPCR 1.0 (n = 2, ExaVir Load v3 (n = 2, and NucliSens EasyQ v2.0 (n = 1. All currently available HIV VL assays are of sufficient sensitivity to detect plasma virus levels at a lower detection limit of 1,000 copies/mL. Bias data comparing the Abbott RealTime HIV-1, TaqMan v2.0 to the Amplicor Monitor v1.5 showed a tendency of the Abbott RealTime HIV-1 to under-estimate results while the TaqMan v2.0 overestimated VL counts. Compared to the Amplicor Monitor v1.5, 2-26% and 9-70% of results from the Versant bDNA 3.0 and Abbott RealTime HIV-1 differed by greater than 0.5log10. The average intra and inter-assay variation of the Abbott RealTime HIV-1 were 2.95% (range 2.0-5.1% and 5.44% (range 1.17-30.00% across the range of VL counts (2log10-7log10. CONCLUSIONS: This review found that all currently available HIV VL assays are of sufficient sensitivity to detect plasma VL of 1,000 copies/mL as a threshold to initiate investigations of treatment adherence or possible treatment failure. Sources of variability between VL assays include differences in technology platform, plasma input volume, and ability to detect HIV-1 subtypes. Monitoring of individual patients should be performed on the same

  18. Viral DNA load of high-risk human papilloma virus is closely associated with the grade of cervical lesions

    OpenAIRE

    Shen, Guqun; Cheng, Jingxin; Wang, Yan; Zhou, Ping; Zhang, Guoqing

    2014-01-01

    This study is to explore the correlation between the viral load of high-risk human papilloma virus (HPV) and the degree of cervical lesions, as well as the follow-up monitoring role of high-risk HPV measurements in the treatment of patients with cervical lesions. Hybrid capture-2 method was used to measure the amount of high-risk HPV load of 361 patients who were enrolled from January 2009 to December 2010 at the Affiliated Tumor Hospital of Xinjiang Medical University, including 76 cases of ...

  19. Predictors of undetectable plasma viral load in HIV-positive adults receiving antiretroviral therapy in Southern Brazil

    Directory of Open Access Journals (Sweden)

    Marysabel Pinto Telis Silveira

    2002-08-01

    Full Text Available Factors associated with undetectable viral load ( or = 95% of adherence (CI 95% 1,80-13,28; CI 95% 1,73-9,53, compared with less than 60% adherence; it was greater for less than 6 months in treatment (OR = 3.37; CI 95% 1.09-10.46; and smaller for viral load previous to adherence measurement > or = 5.2 log10 (OR = 0.19; CI95% 0.06-0.58, adjusted for these variables and sex, age, clinical status, current immune status, group of drugs and interval between the two measurements of viral load. The crude odds were lower for age 16-24 years and use of Nucleoside Analog Reverse Transcriptase Inhibitors only, but these effects were not significant in the multivariate model. There was no evidence of effect of sex, clinical status, current immune status, and changes in treatment regimen. Treatment adherence gave the largest effect. Motivational interventions directed at adherence may improve treatment effectiveness.

  20. Initial viral load determines the magnitude of the human CD8 T cell response to yellow fever vaccination.

    Science.gov (United States)

    Akondy, Rama S; Johnson, Philip L F; Nakaya, Helder I; Edupuganti, Srilatha; Mulligan, Mark J; Lawson, Benton; Miller, Joseph D; Pulendran, Bali; Antia, Rustom; Ahmed, Rafi

    2015-03-10

    CD8 T cells are a potent tool for eliminating intracellular pathogens and tumor cells. Thus, eliciting robust CD8 T-cell immunity is the basis for many vaccines under development. However, the relationship between antigen load and the magnitude of the CD8 T-cell response is not well-described in a human immune response. Here we address this issue by quantifying viral load and the CD8 T-cell response in a cohort of 80 individuals immunized with the live attenuated yellow fever vaccine (YFV-17D) by sampling peripheral blood at days 0, 1, 2, 3, 5, 7, 9, 11, 14, 30, and 90. When the virus load was below a threshold (peak virus load < 225 genomes per mL, or integrated virus load < 400 genome days per mL), the magnitude of the CD8 T-cell response correlated strongly with the virus load (R(2) ∼ 0.63). As the virus load increased above this threshold, the magnitude of the CD8 T-cell responses saturated. Recent advances in CD8 T-cell-based vaccines have focused on replication-incompetent or single-cycle vectors. However, these approaches deliver relatively limited amounts of antigen after immunization. Our results highlight the requirement that T-cell-based vaccines should deliver sufficient antigen during the initial period of the immune response to elicit a large number of CD8 T cells that may be needed for protection.

  1. Deformed wing virus: replication and viral load in mites (Varroa destructor).

    Science.gov (United States)

    Gisder, Sebastian; Aumeier, Pia; Genersch, Elke

    2009-02-01

    Deformed wing virus (DWV) normally causes covert infections but can have devastating effects on bees by inducing morphological deformity or even death when transmitted by the ectoparasitic mite Varroa destructor. In order to determine the role of V. destructor in the development of crippled wings, we analysed individual mites for the presence and replication of DWV. The results supported the correlation between viral replication in mites and morphologically deformed bees. Quantification of viral genome equivalents revealed that mites capable of inducing an overt DWV infection contained 10(10)-10(12) genome equivalents per mite. In contrast, mites which could not induce crippled wings contained a maximum of only 10(8) viral genome equivalents per mite. We conclude that the development of crippled wings not only depends on DWV transmission by V. destructor but also on viral replication in V. destructor and on the DWV titre in the parasitizing mites.

  2. Randomized Controlled Trials to Define Viral Load Thresholds for Cytomegalovirus Pre-Emptive Therapy

    Science.gov (United States)

    Griffiths, Paul D.; Rothwell, Emily; Raza, Mohammed; Wilmore, Stephanie; Doyle, Tomas; Harber, Mark; O’Beirne, James; Mackinnon, Stephen; Jones, Gareth; Thorburn, Douglas; Mattes, Frank; Nebbia, Gaia; Atabani, Sowsan; Smith, Colette; Stanton, Anna; Emery, Vincent C.

    2016-01-01

    Background To help decide when to start and when to stop pre-emptive therapy for cytomegalovirus infection, we conducted two open-label randomized controlled trials in renal, liver and bone marrow transplant recipients in a single centre where pre-emptive therapy is indicated if viraemia exceeds 3000 genomes/ml (2520 IU/ml) of whole blood. Methods Patients with two consecutive viraemia episodes each below 3000 genomes/ml were randomized to continue monitoring or to immediate treatment (Part A). A separate group of patients with viral load greater than 3000 genomes/ml was randomized to stop pre-emptive therapy when two consecutive levels less than 200 genomes/ml (168 IU/ml) or less than 3000 genomes/ml were obtained (Part B). For both parts, the primary endpoint was the occurrence of a separate episode of viraemia requiring treatment because it was greater than 3000 genomes/ml. Results In Part A, the primary endpoint was not significantly different between the two arms; 18/32 (56%) in the monitor arm had viraemia greater than 3000 genomes/ml compared to 10/27 (37%) in the immediate treatment arm (p = 0.193). However, the time to developing an episode of viraemia greater than 3000 genomes/ml was significantly delayed among those randomized to immediate treatment (p = 0.022). In Part B, the primary endpoint was not significantly different between the two arms; 19/55 (35%) in the less than 200 genomes/ml arm subsequently had viraemia greater than 3000 genomes/ml compared to 23/51 (45%) among those randomized to stop treatment in the less than 3000 genomes/ml arm (p = 0.322). However, the duration of antiviral treatment was significantly shorter (p = 0.0012) in those randomized to stop treatment when viraemia was less than 3000 genomes/ml. Discussion The results illustrate that patients have continuing risks for CMV infection with limited time available for intervention. We see no need to alter current rules for stopping or starting pre-emptive therapy. PMID:27684379

  3. Liver Fibrosis progression using Fibroscan in HIV/HCV coinfected patients with undetectable HIV viral load

    Directory of Open Access Journals (Sweden)

    Laura Perez-Martinez

    2014-11-01

    Full Text Available Introduction: Several factors such as duration of infection, age, male gender, consumption of alcohol, HIV infection and low CD4 count have been associated with fibrosis progression rate. However, it is relatively scarce, the knowledge about the liver fibrosis progression rate in HIV-infected patients with undetectable HIV viral load (VL. For this reason, we performed the present study. Materials and Methods: Observational and multicenter study (2008–2012 conducted in four hospitals of the northern Spain. HIV/HCV (hepatitis c virus coinfected patients ≥18 years on stable combination antiretroviral therapy (cART (≥6 months and with a HIV VL <50 copies/mL were selected to analyze their liver fibrosis progression. Fibrosis progression was assessed using a Fibroscan® (502 STEP 3 model and measuring a basal test and a second one at least 12 months apart from baseline. This evolution was compared with different variables such as duration of HIV/HCV coinfection, gender, age, previous treatment for HCV, HCV genotype, CD4 lymphocyte counts and the cART employed at the basal test. Results: A total of 608 patients were included (median age 29.4 years, 71.7% men. Of these, 463 patients met the inclusion criteria. In these patients, the liver fibrosis progression was nearly flat and the only variables related to a higher liver fibrosis progression were the increasing age of the patients (p=0.02 and the duration of the coinfection (p=0.001. CD4 lymphocyte counts showed a tendency to improved liver fibrosis (p=0.056. Conclusions: In HIV/HCV coinfected patients on stable cART and HIV undetectable VL, the increase in liver fibrosis rate progression was nearly flat, although it was significantly associated with the duration of the coinfection and the age of the patient. The beneficial effects of the cART were independent of the antiretroviral drug employed. A tendency to a lower fibrosis progression was observed in those patients with a higher CD4 count.

  4. Service impact of a change in HIV-1 viral load quantification assay

    Directory of Open Access Journals (Sweden)

    Craig Tipple

    2014-11-01

    Full Text Available Introduction: Due to discontinuation of the Siemens Versant HIV-1 RNA (bDNA assay in the UK, our laboratory switched to the Roche Cobas Ampliprep/Taqman HIV-1 viral load (VL assay (Roche in April 2013. This assay has a lower cut-off of 20 RNA copies/mL (compared with <50 for the Siemens assay. Our laboratory demonstrated previously that a significant proportion (18% of patients undetectable using bDNA HIV-1 RNA quantification exhibited low level viraemia (LLV using the new assay. Local guidelines recommend that patients stable on therapy receive twice-yearly VLs. We evaluated the impact of the introduction of the new assay on our clinical service. Methods: A retrospective cohort analysis of treated patients with stable undetectable VL by bDNA (<50 copies/mL followed by ≥ one low-level (<400 copies/mL VL with the Roche assay. Demographic data were collected in addition to frequency of VL testing and genotypic resistance assays. Referrals to virtual clinic (VC were recorded. Patients were identified using laboratory data and information collected from electronic patient records. Results were analyzed with SPSS v18. Results: One hundred and ninety patients were included. Demographics: 79.5% male; 60.6% homosexual; mean age of 46 years. Duration on stable treatment was 46.35 (std. dev. 38.15 months. Current treatment regimens were 43.3% PI-based; 43.3% NNRTI-based and 13.7% other. Patients were stratified into VL 20–49 copies/mL (n=109; VL 50–199 copies/mL (n=71 and VL 200–399 copies/mL (n=10. In total, there were 471 VLs measured of which 274 were additional as a result of the assay switch. This resulted in six HIV-1 genotype requests and 16 VC discussions (Table 1. Longer duration on HAART was associated with reduced frequency of VL testing. The relative risk of ongoing detectability according to drug class are: PI 1.62 (95% CI 1.18–2.21; NNRTI 0.507 (95% CI 0.30–0.85 and other 1.09 (95% CI 0.48–2.43. Conclusions: Changes in assay

  5. Spontaneous viral clearance, viral load, and genotype distribution of hepatitis C virus (HCV) in HIV-infected patients with anti-HCV antibodies in Europe

    DEFF Research Database (Denmark)

    Soriano, Vincent; Mocroft, Amanda; Rockstroh, Juergen

    2008-01-01

    for hepatitis B surface antigen (HBsAg) were more likely to have spontaneously cleared HCV than were those negative for HBsAg (43% vs. 21%; aOR, 2.91 [95% CI, 1.94-4.38]). Of patients with HCV viremia, 786 (53%) carried HCV genotype 1, and 53 (4%), 440 (29%), and 217 (15%) carried HCV genotype 2, 3, and 4...... in IDUs and, conversely, was less common in HBsAg-positive patients. Of the patients with HCV viremia analyzed, 53% were found to carry HCV genotype 1, and this genotype was associated with greater serum HCV RNA levels....

  6. The effect of antioxidant supplementation on hepatitis C viral load, transaminases and oxidative status: a randomized trial among chronic hepatitis C virus-infected patients

    DEFF Research Database (Denmark)

    Groenbaek, K.; Friis, H.; Hansen, Max;

    2006-01-01

    Objective To assess the effect of antioxidant supplementation on hepatitis C viral load, transaminases and oxidative status. Methods We performed a randomized, placebo-controlled, double-blind trial to assess the effect of antioxidant supplementation on serum alanine aminotransferase, plasma hepa...... and catalase) or plasma levels of oxidative markers (malondialdehyde and 2-amino-adipic semialdehyde) were found. Conclusion Supplementation with vitamin C, E and selenium increased the antioxidant status, but had no effects on alanine aminotransferase, viral load or oxidative markers....

  7. CD4 cell count and viral load-specific rates of AIDS, non-AIDS and deaths according to current antiretroviral use

    DEFF Research Database (Denmark)

    Mocroft, Amanda; Phillips, Andrew N; Gatell, Jose

    2013-01-01

    CD4 cell count and viral loads are used in clinical trials as surrogate endpoints for assessing efficacy of newly available antiretrovirals. If antiretrovirals act through other pathways or increase the risk of disease this would not be identified prior to licensing. The aim of this study was to ...... was to investigate the CD4 cell count and viral load-specific rates of fatal and nonfatal AIDS and non-AIDS events according to current antiretrovirals....

  8. Systematic review of the use of dried blood spots for monitoring HIV viral load and for early infant diagnosis.

    Directory of Open Access Journals (Sweden)

    Pieter W Smit

    Full Text Available BACKGROUND: Dried blood spots (DBS have been used as alternative specimens to plasma to increase access to HIV viral load (VL monitoring and early infant diagnosis (EID in remote settings. We systematically reviewed evidence on the performance of DBS compared to plasma for VL monitoring and EID. METHODS AND FINDINGS: Thirteen peer reviewed HIV VL publications and five HIV EID papers were included. Depending on the technology and the viral load distribution in the study population, the percentage of DBS samples that are within 0.5 log of VL in plasma ranged from 52-100%. Because the input sample volume is much smaller in a blood spot, there is a risk of false negatives with DBS. Sensitivity of DBS VL was found to be 78-100% compared to plasma at VL below 1000 copies/ml, but this increased to 100% at a threshold of 5000 copies/ml. Unlike a plasma VL test which measures only cell free HIV RNA, a DBS VL also measures proviral DNA as well as cell-associated RNA, potentially leading to false positive results when using DBS. The systematic review showed that specificity was close to 100% at DBS VL above 5000 copies/ml, and this threshold would be the most reliable for predicting true virologic failure using DBS. For early infant diagnosis, DBS has a sensitivity of 100% compared to fresh whole blood or plasma in all studies. CONCLUSIONS: Although limited data are available for EID, DBS offer a highly sensitive and specific sampling strategy to make viral load monitoring and early infant diagnosis more accessible in remote settings. A standardized approach for sampling, storing, and processing DBS samples would be essential to allow successful implementation. TRIAL REGISTRATION: PROSPERO Registration #: CRD42013003621.

  9. Systematic Review of the Use of Dried Blood Spots for Monitoring HIV Viral Load and for Early Infant Diagnosis

    Science.gov (United States)

    Smit, Pieter W.; Sollis, Kimberly A.; Fiscus, Susan; Ford, Nathan; Vitoria, Marco; Essajee, Shaffiq; Barnett, David; Cheng, Ben; Crowe, Suzanne M.; Denny, Thomas; Landay, Alan; Stevens, Wendy; Habiyambere, Vincent; Perriens, Joseph H.; Peeling, Rosanna W.

    2014-01-01

    Background Dried blood spots (DBS) have been used as alternative specimens to plasma to increase access to HIV viral load (VL) monitoring and early infant diagnosis (EID) in remote settings. We systematically reviewed evidence on the performance of DBS compared to plasma for VL monitoring and EID. Methods and Findings Thirteen peer reviewed HIV VL publications and five HIV EID papers were included. Depending on the technology and the viral load distribution in the study population, the percentage of DBS samples that are within 0.5 log of VL in plasma ranged from 52–100%. Because the input sample volume is much smaller in a blood spot, there is a risk of false negatives with DBS. Sensitivity of DBS VL was found to be 78–100% compared to plasma at VL below 1000 copies/ml, but this increased to 100% at a threshold of 5000 copies/ml. Unlike a plasma VL test which measures only cell free HIV RNA, a DBS VL also measures proviral DNA as well as cell-associated RNA, potentially leading to false positive results when using DBS. The systematic review showed that specificity was close to 100% at DBS VL above 5000 copies/ml, and this threshold would be the most reliable for predicting true virologic failure using DBS. For early infant diagnosis, DBS has a sensitivity of 100% compared to fresh whole blood or plasma in all studies. Conclusions Although limited data are available for EID, DBS offer a highly sensitive and specific sampling strategy to make viral load monitoring and early infant diagnosis more accessible in remote settings. A standardized approach for sampling, storing, and processing DBS samples would be essential to allow successful implementation. Trial Registration PROSPERO Registration #: CRD42013003621. PMID:24603442

  10. Impact of polymorphisms in the HCP5 and HLA-C, and ZNRD1 genes on HIV viral load

    DEFF Research Database (Denmark)

    Thørner, Lise Wegner; Erikstrup, Christian; Harritshøj, Lene Holm;

    2016-01-01

    AIMS: Single nucleotide polymorphisms (SNPs) in the human leucocyte antigen (HLA) complex P5 (HCP5), HLA-C, and near the zinc ribbon domain containing 1 (ZNRD1) have been shown to influence viral load (VL) set point in HIV-infected individuals with a known seroconversion onset. We aimed to determ......AIMS: Single nucleotide polymorphisms (SNPs) in the human leucocyte antigen (HLA) complex P5 (HCP5), HLA-C, and near the zinc ribbon domain containing 1 (ZNRD1) have been shown to influence viral load (VL) set point in HIV-infected individuals with a known seroconversion onset. We aimed......>C), rs9264942 (T>C), and rs3869068 (C>T) SNPs in 1897 Caucasians from The Danish HIV Cohort Study - a prospective, nationwide, population-based study of HIV-infected individuals in Denmark. General linear models evaluated the effect of SNPs on VL in antiretroviral-naïve individuals 0-18months after...... diagnosis and on CD4(+) T-cell recovery during cART. Cox proportional hazard regression analysis assessed the association with time to first VL

  11. Kinetics of viral load and erythrocytic inclusion body formation in pacific herring artificially infected with erythrocytic necrosis virus

    Science.gov (United States)

    Glenn, Jolene A.; Emmenegger, Eveline J.; Grady, Courtney A.; Roon, Sean R.; Gregg, Jacob L.; Conway, Carla M.; Winton, James R.; Hershberger, Paul K.

    2012-01-01

    Viral erythrocytic necrosis (VEN) is a condition that affects marine and anadromous fish species, including herrings and salmonids, in the Atlantic and Pacific oceans. Infection is frequently associated with severe anemia and causes episodic mortality among wild and hatchery fish when accompanied by additional stressors; VEN can be presumptively diagnosed by (1) light microscopic identification of a single characteristic—a round, magenta-colored, 0.8-μm-diameter inclusion body (IB) within the cytoplasm of erythrocytes and their precursors on Giemsa-stained blood films; or (2) observation (via transmission electron microscopy [TEM]) of the causative iridovirus, erythrocytic necrosis virus (ENV), within erythrocytes or their precursors. To better understand the kinetics of VEN, specific-pathogen-free Pacific herring Clupea pallasii were infected with ENV by intraperitoneal injection. At 1, 4, 7, 10, 14, 21, and 28 d postexposure, samples of blood, spleen, and kidney were collected and assessed (1) via light microscopy for the number of intracytoplasmic IBs in blood smears and (2) via TEM for the number of virions within erythrocytes. The mean prevalence of intracytoplasmic IBs in the blood cells increased from 0% at 0–4 d postexposure to 94% at 28 d postexposure. Viral load within circulating red blood cells peaked at 7 d postexposure, fell slightly, and then reached a plateau. However, blood cells observed within the kidney and spleen tissues demonstrated high levels of ENV between 14 and 28 d postexposure. The results indicate that the viral load within erythrocytes does not correlate well with IB prevalence and that the virus can persist in infected fish for more than 28 d.

  12. Combined antiretroviral therapy reduces brain viral load and pathological features of HIV encephalitis in a mouse model.

    Science.gov (United States)

    Koneru, Rajeth; Olive, M Foster; Tyor, William R

    2014-02-01

    The role of brain HIV load in the pathogenesis of HIV-associated neurocognitive disorders (HAND) is unclear. To try and determine if the amount of HIV drives the severity of pathology, a severe combined immunodeficient (SCID) mouse model of HIV encephalitis (HIVE) was utilized to determine the effectiveness of a systemically administered combined antiretroviral (cART) regimen. SCID mice were inoculated intracerebrally with HIV-infected or uninfected (control) human macrophages and treated subcutaneously with cART or saline for 10 days. Immunohistochemistry was then used to examine gliosis and neuronal damage. Drug levels were measured in brain and plasma using high-performance liquid chromatography. Peak plasma and brain levels of atazanavir, tenofovir, and emtricitabine were determined to be 1 h post-injection of cART therapy. cART significantly reduced neuropathological features of HIVE, including astrogliosis and the presence of mononuclear phagocytes, and ameliorated reduced MAP2 (neuronal integrity) staining. However, cART did not eradicate HIV from the brain. Using this animal model of HIVE, these data indicate effective penetration of cART reduces brain viral loads and HIV pathology, possibly by eliminating the production of HIV proteins, virus infected cells, or both. Importantly, these data suggest that viral load directly affects the extent of pathology seen in the brain, particularly neuronal damage, which implies that more effective suppression of HIV in the CNS could reduce currently highly prevalent forms of HAND. However, these data also strongly suggest that cART will not eliminate HIV from the brain and that adjunctive therapies must be developed.

  13. The Breadth of Expandable Memory CD8+ T Cells Inversely Correlates with Residual Viral Loads in HIV Elite Controllers

    Science.gov (United States)

    Ndhlovu, Zaza M.; Stampouloglou, Eleni; Cesa, Kevin; Mavrothalassitis, Orestes; Alvino, Donna Marie; Li, Jonathan Z.; Wilton, Shannon; Karel, Daniel; Piechocka-Trocha, Alicja; Chen, Huabiao; Pereyra, Florencia

    2015-01-01

    ABSTRACT Previous studies have shown that elite controllers with minimal effector T cell responses harbor a low-frequency, readily expandable, highly functional, and broadly directed memory population. Here, we interrogated the in vivo relevance of this cell population by investigating whether the breadth of expandable memory responses is associated with the magnitude of residual viremia in individuals achieving durable suppression of HIV infection. HIV-specific memory CD8+ T cells were expanded by using autologous epitopic and variant peptides. Viral load was measured by an ultrasensitive single-copy PCR assay. Following expansion, controllers showed a greater increase in the overall breadth of Gag responses than did untreated progressors (P = 0.01) as well as treated progressors (P = 0.0003). Nef- and Env-specific memory cells expanded poorly for all groups, and their expanded breadths were indistinguishable among groups (P = 0.9 for Nef as determined by a Kruskal-Wallis test; P = 0.6 for Env as determined by a Kruskal-Wallis test). More importantly, we show that the breadth of expandable, previously undetectable Gag-specific responses was inversely correlated with residual viral load (r = −0.6; P = 0.009). Together, these data reveal a direct link between the abundance of Gag-specific expandable memory responses and prolonged maintenance of low-level viremia. Our studies highlight a CD8+ T cell feature that would be desirable in a vaccine-induced T cell response. IMPORTANCE Many studies have shown that the rare ability of some individuals to control HIV infection in the absence of antiretroviral therapy appears to be heavily dependent upon special HIV-specific killer T lymphocytes that are able to inhibit viral replication. The identification of key features of these immune cells has the potential to inform rational HIV vaccine design. This study shows that a special subset of killer lymphocytes, known as central memory CD8+ T lymphocytes, is at least

  14. Genome-wide association study confirming association of HLA-DP with protection against chronic hepatitis B and viral clearance in Japanese and Korean.

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    Nao Nishida

    Full Text Available Hepatitis B virus (HBV infection can lead to serious liver diseases, including liver cirrhosis (LC and hepatocellular carcinoma (HCC; however, about 85-90% of infected individuals become inactive carriers with sustained biochemical remission and very low risk of LC or HCC. To identify host genetic factors contributing to HBV clearance, we conducted genome-wide association studies (GWAS and replication analysis using samples from HBV carriers and spontaneously HBV-resolved Japanese and Korean individuals. Association analysis in the Japanese and Korean data identified the HLA-DPA1 and HLA-DPB1 genes with P(meta = 1.89×10⁻¹² for rs3077 and P(meta = 9.69×10⁻¹⁰ for rs9277542. We also found that the HLA-DPA1 and HLA-DPB1 genes were significantly associated with protective effects against chronic hepatitis B (CHB in Japanese, Korean and other Asian populations, including Chinese and Thai individuals (P(meta = 4.40×10⁻¹⁹ for rs3077 and P(meta = 1.28×10⁻¹⁵ for rs9277542. These results suggest that the associations between the HLA-DP locus and the protective effects against persistent HBV infection and with clearance of HBV were replicated widely in East Asian populations; however, there are no reports of GWAS in Caucasian or African populations. Based on the GWAS in this study, there were no significant SNPs associated with HCC development. To clarify the pathogenesis of CHB and the mechanisms of HBV clearance, further studies are necessary, including functional analyses of the HLA-DP molecule.

  15. PREVALENCE OF HEPATITIS C AMONG EGYPTIAN CHILDREN WITH SICKLE CELL DISEASE AND THE ROLE OF IL28B GENE POLYMORPHISMS IN SPONTANEOUS VIRAL CLEARANCE

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    Somaia Mohammed Mousa

    2016-01-01

    Full Text Available Background and objectives: Hepatitis C virus (HCV is a major health problem in Egypt with its prevalence estimated to be 14.7% among general population in 2008. Patients receiving frequent blood transfusions like sickle cell disease (SCD are more exposed to the risk of acquiring HCV. IL28B gene polymorphisms have been associated with spontaneous HCV clearance. This study aims to determine the prevalence of HCV infection among children with SCD and to study the relation between IL28B gene polymorphisms and spontaneous HCV clearance. Methods: Seventy SCD patients were screened for HCV antibody. HCV positive patients were tested for the level of HCV RNA using quantitative real time PCR. IL28B polymorphisms (rs 12979860 SNP and rs 12980275 SNP were detected using Taqman QRT-PCR and sequence specific primers PCR respectively. Results: Sixteen patients (23% were HCV antibody positive, 9 of them (56.3% had undetectable HCV RNA in serum and 7 (43.7% had persistent viremia. Genotypes CC/CT/TT of rs12979860 were found in 30 (42.9%, 29 (41.4% and 11 (15.7% and rs12980275 AA/AG/GG were found in 8 (11.4%, 59 (84.3% and 3 (4.3%.  There was no significant difference in the frequency of IL28B (rs 12979860 and rs12980275 genotypes among HCV patients who cleared the virus and those with persistent viremia (p=0.308 and 0.724 respectively.  Conclusion: Egyptian SCD patients have high prevalence of HCV. Muti-transfused patients still exposed to a risk of transmission of HCV. IL28B gene polymorphisms are not associated with spontaneous clearance of HCV in this cohort of Egyptian children with SCD.

  16. Prevalence of Hepatitis C among Egyptian Children with Sickle Cell Disease and the Role of IL28b Gene Polymorphisms in Spontaneous Viral Clearance

    Science.gov (United States)

    Mousa, Somaia Mohammed; El-Ghamrawy, Mona Kamal; Gouda, Heba; Khorshied, Mervat; El-Salam Ahmed, Dina Abd; Shiba, Hala

    2016-01-01

    Background and Objectives Hepatitis C virus (HCV) is a major health problem in Egypt with its prevalence estimated to be 14.7% among the general population in 2008. Patients receiving frequent blood transfusions like those with sickle cell disease (SCD) are more exposed to the risk of acquiring HCV. IL28B gene polymorphisms have been associated with spontaneous HCV clearance. This study aims to determine the prevalence of HCV infection among children with SCD and to investigate the relation between IL28B gene polymorphisms and spontaneous HCV clearance. Methods Seventy SCD patients were screened for HCV antibody. HCV-positive patients were tested for the level of HCV RNA using quantitative real-time PCR. IL28B polymorphisms (rs 12979860 SNP and rs 12980275 SNP) were detected using TaqMan QRT-PCR and sequence-specific primers PCR respectively. Results Sixteen patients (23%) were HCV antibody positive, 9 of them (56.3%) had undetectable HCV RNA in serum, and 7 (43.7%) had persistent viremia. Genotypes CC/CT/TT of rs12979860 were found in 30 (42.9%), 29 (41.4%) and 11 (15.7%) patients and rs12980275 AA/AG/GG were found in 8 (11.4%), 59 (84.3%) and 3 (4.3%) patients. There was no significant difference in the frequency of IL28B (rs 12979860 and rs12980275) genotypes among HCV patients who cleared the virus and those with persistent viremia (p=0.308 and 0.724 respectively). Conclusion Egyptian SCD patients have a high prevalence of HCV. Multi-transfused patients still exposed to the risk of transmission of HCV. IL28B gene polymorphismsare not associated with spontaneous clearance of HCV in this cohort of Egyptian children with SCD. PMID:26740868

  17. Cost-Effectiveness of Testing Hepatitis B–Positive Pregnant Women for Hepatitis B e Antigen or Viral Load

    Science.gov (United States)

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

    2015-01-01

    OBJECTIVE To estimate the cost-effectiveness of testing pregnant women with hepatitis B (hepatitis B surface antigen [HBsAg]-positive) for hepatitis B e antigen (HBeAg) or hepatitis B virus (HBV) DNA, and administering maternal antiviral prophylaxis if indicated, to decrease breakthrough perinatal HBV transmission from the U.S. health care perspective. METHODS A Markov decision model was constructed for a 2010 birth cohort of 4 million neonates to estimate the cost-effectiveness of two strategies: testing HBsAg-positive pregnant women for 1) HBeAg or 2) HBV load. Maternal antiviral prophylaxis is given from 28 weeks of gestation through 4 weeks postpartum when HBeAg is positive or HBV load is high (108 copies/mL or greater). These strategies were compared with the current recommendation. All neonates born to HBsAg-positive women received recommended active-passive immunoprophylaxis. Effects were measured in quality-adjusted life-years (QALYs) and all costs were in 2010 U.S. dollars. RESULTS The HBeAg testing strategy saved $3.3 million and 3,080 QALYs and prevented 486 chronic HBV infections compared with the current recommendation. The HBV load testing strategy cost $3 million more than current recommendation, saved 2,080 QALYs, and prevented 324 chronic infections with an incremental cost-effectiveness ratio of $1,583 per QALY saved compared with the current recommendations. The results remained robust over a wide range of assumptions. CONCLUSION Testing HBsAg-positive pregnant women for HBeAg or HBV load followed by maternal antiviral prophylaxis if HBeAg-positive or high viral load to reduce perinatal hepatitis B transmission in the United States is cost-effective. PMID:24785842

  18. Effect of Monotherapy with Darunavir/Ritonavir on Viral Load in Seminal Fluid, and Quality Parameters of Semen in HIV-1-Positive Patients

    Science.gov (United States)

    Lopez-Ruz, Miguel A.; Navas, Purificación; López-Zúñiga, Miguel A.; Gonzalvo, María Carmen; Sampedro, Antonio; Pasquau, Juan; Hidalgo-Tenorio, Carmen; Javier, Rosario; Castilla, José A.

    2016-01-01

    Patients with human immunodeficiency virus type 1 (HIV-1) who receive antiretroviral therapy (ART) often achieve increased survival and improved quality of life. In this respect, monotherapy with darunavir/ritonavir (mDRV/r) can be a useful treatment strategy. This prospective study analyses the effect of mDRV/r on sperm quality and viral load in a group of 28 patients who had previously been given conventional ART and who had recorded a viral load 20 copies/ml), and that at V1, after mDRV/r treatment, this figure had fallen to 3%. The quality of seminal fluid was close to normal in 57% of patients at V0 and in 62% at V1. We conclude that, similar to ART, mDRV/r maintains HIV-1 viral load in most patients, and that there is no worsening in seminal fluid quality. PMID:27442068

  19. Relationship between hepatitis C virus genotypes and viral load in Chenzhou,China

    Institute of Scientific and Technical Information of China (English)

    谷斌

    2014-01-01

    Objective To investigate the epidemiological characteristics of hepatitis C and the genotypes of hepatitis C virus(HCV)in Chenzhou,Hunan Province,China,and to analyze the difference in HCV RNA load between genotype 1 patients and non-genotype 1 patients.Methods Sixty hepatitis C patients with positive HCV RNA,who were from Chenzhou and received initial treatment in our hospital from March 2012 to March 2013,were included in the study.HCV RNA load and HCV genotypes were determined,and

  20. Mucociliary clearance

    DEFF Research Database (Denmark)

    Munkholm, Mathias; Mortensen, Jann

    2014-01-01

    Mucociliary clearance has long been known to be a significant innate defence mechanism against inhaled microbes and irritants. Important knowledge has been gathered regarding the anatomy and physiology of this system, and in recent years, extensive studies of the pathophysiology related to lung...... pharmacological interventions on clearance rate, to study the importance of defective mucus clearance in different lung diseases or as a diagnostic tool in the work-up of patients with recurrent airway diseases. The aim of this review is to provide an overview of the anatomy, physiology, pathophysiology...

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

    NARCIS (Netherlands)

    Falco Gracia, J.A.; Barrajon-Catalan, E.; Menendez-Gutierrez, M.P.; Coll, J.; Micol, V.; Estepa, A.

    2013-01-01

    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 adap

  2. Hepatitis B virus: pathogenesis, viral intermediates, and viral replication.

    Science.gov (United States)

    Lee, Jia-Yee; Locarnini, Stephen

    2004-05-01

    Although HBV has the potential to generate an almost limitless spectrum of quasispecies during chronic infection, the viability of the majority of these quasispecies is almost certainly impaired due to constraints imposed by the remarkably compact organization of the HBV genome. On the other hand, single mutations may affect more than one gene and result in complex and unpredictable effects on viral phenotype. Better understanding of the constraints imposed by gene overlap and of genotype-phenotype relationships should help in the development of improved antiviral strategies and management approaches. Although the probability of developing viral resistance is directly proportional to the intensity of selection pressure and the diversity of quasispecies, potent inhibition of HBV replication should be able to prevent development of drug resistance because mutagenesis is replication dependent. If viral replication can be suppressed for a sufficient length of time, viral load should decline to a point where the continued production of quasispecies with the potential to resist new drug treatments no longer occurs. Clinical application of this concept will require optimization of combination therapies analogous to highly active antiretroviral therapy (HAART) for HIV infection. Total cure of hepatitis B will require elimination of the intranuclear pool of viral minichromosomes, which will probably only be achieved by normal cell turnover, reactivation of host immunity, or elucidation of the antiviral mechanisms operating during cytokine clearance in acute hepatitis B (see Fig. 1).

  3. Dynamics of CD4 Lymphocytes and Viral Load at the Natural History of Perinatal HIV-infection

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    T. A. Daminov

    2015-01-01

    Full Text Available This article presents the analysis of indicators of CD4 lymphocyte count and viral load in the natural history (in the absence of ART in perinatally HIV-infected children. It was revealed that perinatal way of transmission is characterized by a higher rate of immunodeficiency progression. It may be associated with intrauterine infection, as well as an early defeat HIV immature immune system of the child. The concentration of virus in perinatally infected children since the beginning of the observation and in 30 months after infection is more than in parenterally infected children in 5 and 2 times, respectively, which determines a infavourable version of the disease in perinatally infected children.

  4. CD4 count and viral load specific rates of AIDS, non-AIDS and deaths according to current antiretroviral use

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    A Mocroft

    2012-11-01

    Full Text Available Background CD4 and viral loads are used in clinical trials as surrogate endpoints for assessing efficacy of newly available antiretrovirals. If antiretrovirals act through other pathways or negatively affect the risk of disease this would not be identified prior to licensing. The aims of this study were to investigate the CD4 and viral load specific rates of fatal and non-fatal AIDS and non-AIDS events according to current antiretrovirals. Methods Poisson regression was used to compare overall events (fatal or non-fatal AIDS, non-AIDS or death, AIDS events (fatal and non-fatal or non-AIDS events (fatal or non-fatal for specific nucleoside pairs and third drugs used with>1000 person-years of follow-up (PYFU after January 1st 2001. Results 9801 patients were included. The median baseline date was January 2004 (interquartile range [IQR] January 2001–February 2007, age was 40.4 (IQR 34.6–47.3 years, and time since starting cART was 3.3 (IQR 0.9–5.1 years. At baseline, the median nadir CD4 was 162 (IQR 71–257/mm3, baseline CD4 was 390 (IQR 249–571/mm3, viral load was 1.9 (IQR 1.7–3.3 log10copies/ml and 2961 (30.2% had a prior AIDS diagnosis and 6.4 years prior to baseline. During 42372.5 PYFU, 1203 (437 AIDS and 766 non-AIDS events occurred. The overall event rate was 2.8 per 100 PYFU (95% confidence interval [CI] 2.7–3.0, of AIDS events was 1.0 (95% CI 0.9–1.1 and of non-AIDS events was 1.8 (95% CI 1.7–1.9. Of the AIDS events, 53 (12.1%were fatal as were 239 (31.2% of the non-AIDS events. After adjustment, there was weak evidence of a difference in the overall events rates between nucleoside pairs (global p-value=0.084, and third drugs (global p-value=0.031. Compared to zidovudine/lamivudine, patients taking abacavir/lamivudine (adjusted incidence rate ratio [aIRR] 1.22; 95% CI 0.99–1.49 and abacavir plus one other nucleoside (aIRR 1.51; 95% CI 1.14–2.02 had an increased incidence of overall events. Comparing the third drugs

  5. Human platelets antigens influence the viral load of platelets after the interaction of the platelets with HCV and HIV in vitro

    Directory of Open Access Journals (Sweden)

    Rejane Maria Tommasini Grotto

    Full Text Available Abstract: INTRODUCTION: In this study, we evaluated hepatitis C virus (HCV and human immunodeficiency virus (HIV - platelet interactions in vitro as well as human platelets antigen (HPA polymorphisms. METHODS: Platelets were obtained from 100 healthy HPA-genotyped volunteer donors and incubated with HIV or HCV. The viral load after in vitro exposure was detected. RESULTS: The viral load in the platelets after exposure to the virus was higher in the HIV exposure than in the HCV exposure. CONCLUSIONS: HIV-platelet ligation could be more efficient than HCV-platelet interaction. Further, the HPA-1b allele seems to influence the interaction of platelets with HCV.

  6. Human papillomavirus prevalence, viral load and pre-cancerous lesions of the cervix in women initiating highly active antiretroviral therapy in South Africa: a cross-sectional study

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    Rybicki Ed

    2009-08-01

    Full Text Available Abstract Background Cervical cancer and infection with human immunodeficiency virus (HIV are both important public health problems in South Africa (SA. The aim of this study was to determine the prevalence of cervical squamous intraepithelial lesions (SILs, high-risk human papillomavirus (HR-HPV, HPV viral load and HPV genotypes in HIV positive women initiating anti-retroviral (ARV therapy. Methods A cross-sectional survey was conducted at an anti-retroviral (ARV treatment clinic in Cape Town, SA in 2007. Cervical specimens were taken for cytological analysis and HPV testing. The Digene Hybrid Capture 2 (HC2 test was used to detect HR-HPV. Relative light units (RLU were used as a measure of HPV viral load. HPV types were determined using the Roche Linear Array HPV Genotyping test. Crude associations with abnormal cytology were tested and multiple logistic regression was used to determine independent risk factors for abnormal cytology. Results The median age of the 109 participants was 31 years, the median CD4 count was 125/mm3, 66.3% had an abnormal Pap smear, the HR-HPV prevalence was 78.9% (Digene, the median HPV viral load was 181.1 RLU (HC2 positive samples only and 78.4% had multiple genotypes. Among women with abnormal smears the most prevalent HR-HPV types were HPV types 16, 58 and 51, all with a prevalence of 28.5%. On univariate analysis HR-HPV, multiple HPV types and HPV viral load were significantly associated with the presence of low and high-grade SILs (LSIL/HSIL. The multivariate logistic regression showed that HPV viral load was associated with an increased odds of LSIL/HSIL, odds ratio of 10.7 (95% CI 2.0 – 57.7 for those that were HC2 positive and had a viral load of ≤ 181.1 RLU (the median HPV viral load, and 33.8 (95% CI 6.4 – 178.9 for those that were HC2 positive with a HPV viral load > 181.1 RLU. Conclusion Women initiating ARVs have a high prevalence of abnormal Pap smears and HR-HPV. Our results underscore the need

  7. Mucosal immunization with recombinant adenoviral vectors expressing murine gammaherpesvirus-68 genes M2 and M3 can reduce latent viral load

    DEFF Research Database (Denmark)

    Hoegh-Petersen, Mette; Thomsen, Allan R; Christensen, Jan P

    2009-01-01

    of the gammaherpesvirinae speaks against using a similar approach in humans. DNA immunization with plasmids encoding the MHV-68 genes M2 or M3 caused a reduction in either acute or early latent viral load, respectively, but neither immunization had an effect at times later than 14 days post-infection. Adenovirus......-based vaccines are substantially more immunogenic than DNA vaccines and can be applied to induce mucosal immunity. Here we show that a significant reduction of the late viral load in the spleens, at 60 days post-infection, was achieved when immunizing mice both intranasally and subcutaneously with adenoviral...

  8. High levels of T lymphocyte activation in Leishmania-HIV-1 co-infected individuals despite low HIV viral load

    Directory of Open Access Journals (Sweden)

    Grinsztejn Beatriz

    2010-12-01

    Full Text Available Abstract Background Concomitant infections may influence HIV progression by causing chronic activation leading to decline in T-cell function. In the Americas, visceral (AVL and tegumentary leishmaniasis (ATL have emerged as important opportunistic infections in HIV-AIDS patients and both of those diseases have been implicated as potentially important co-factors in disease progression. We investigated whether leishmaniasis increases lymphocyte activation in HIV-1 co-infected patients. This might contribute to impaired cellular immune function. Methods To address this issue we analyzed CD4+ T absolute counts and the proportion of CD8+ T cells expressing CD38 in Leishmania/HIV co-infected patients that recovered after anti-leishmanial therapy. Results We found that, despite clinical remission of leishmaniasis, AVL co-infected patients presented a more severe immunossupression as suggested by CD4+ T cell counts under 200 cells/mm3, differing from ATL/HIV-AIDS cases that tends to show higher lymphocytes levels (over 350 cells/mm3. Furthermore, five out of nine, AVL/HIV-AIDS presented low CD4+ T cell counts in spite of low or undetectable viral load. Expression of CD38 on CD8+ T lymphocytes was significantly higher in AVL or ATL/HIV-AIDS cases compared to HIV/AIDS patients without leishmaniasis or healthy subjects. Conclusions Leishmania infection can increase the degree of immune system activation in individuals concomitantly infected with HIV. In addition, AVL/HIV-AIDS patients can present low CD4+ T cell counts and higher proportion of activated T lymphocytes even when HIV viral load is suppressed under HAART. This fact can cause a misinterpretation of these laboratorial markers in co-infected patients.

  9. Evaluation of histopathological changes, viral load and immune function of domestic geese infected with Newcastle disease virus.

    Science.gov (United States)

    Lu, Ailing; Diao, Youxiang; Chen, Hao; Wang, Jiao; Ge, Pingping; Sun, Xiaoyan; Hao, Dongmin

    2014-01-01

    Outbreaks of Newcastle disease in flocks of geese with high morbidity and mortality in southern and eastern China have been reported frequently since the late 1990s, which broke the traditional view that geese are considered to be the natural reservoir of Newcastle disease virus (NDV) but show few or no clinical signs after infection. In this present study, geese were infected intranasally with a local strain of NDV. Clinical disease and gross pathology were observed. Serum and immune organs were collected from geese sequentially euthanized or after disease-associated death. We studied the histopathology of immune organs by haematoxylin and eosin staining and NDV fusion protein was detected in tissues by immunohistochemistry. At the same time, the SYBR Green I real-time polymerase chain reaction assay was used to detect the viral load from the collected samples. Serum samples were tested for NDV-specific antibodies and avian influenza virus (AIV)-specific antibodies by haemagglutination inhibition (HI) test. The results showed that severe lesions and numerous positive reactions of NDV antigen were detected in the immune organs. High viral loads developed in immune organs of infected geese, correlating with the severity of clinical signs and lesions in the tissues. Furthermore, the infected geese developed low HI antibody titres to both AIV and NDV. The present study showed that the replication and dissemination of the NDV isolate was widespread in immune organs of geese. The study revealed that waterfowl may not only be a natural reservoir of NDV but also become susceptible to disease and may play a major role in the epidemiology of Newcastle disease.

  10. Dry Blood Spots a Reliable Method for Measurement of Hepatitis B Viral Load in Resource-Limited Settings

    Science.gov (United States)

    Stene-Johansen, Kathrine; Yaqoob, Nadeem; Overbo, Joakim; Aberra, Hanna; Desalegn, Hailemichael; Berhe, Nega; Johannessen, Asgeir

    2016-01-01

    Background & Aims Hepatitis B virus (HBV) quantification is essential in the management of chronic hepatitis B, both to determine treatment eligibility and in the monitoring of treatment effect. This test, however, is rarely available in resource-limited settings due to high costs and stringent requirements for shipment and storage of plasma. Dried Blood Spots (DBS) can be a convenient alternative to plasma, but its use for HBV monitoring has not been investigated under real-life conditions in Africa. Methods The performance of DBS in HBV quantification was investigated using a modified commercial test (Abbott RealTime HBV assay). Paired DBS and plasma samples were collected from an HBV positive cohort in Addis Ababa, Ethiopia. DBS were stored at ambient temperature for 4–39 days before shipment to the laboratory. Results Twenty-six paired samples were selected covering the total range of quantification, from 2.14 log IU/ml to >7 log IU/ml. HBV was detected in 21 of 21 (100%) DBS from patients with a corresponding plasma viral load above 2.70 log IU/ml. The mean difference between plasma and DBS was 0.59 log IU/ml, and the correlation was strong (R2 = 0.92). In stability studies there was no significant change in DBS viral load after storage at room temperature for up to 12 weeks. Conclusions This study suggests that DBS can be a feasible and reliable alternative to plasma for quantification of HBV in resource-limited settings. DBS can expand access to antiviral treatment for patients in low- and middle-income countries. PMID:27820845

  11. Mutagenesis-mediated virus extinction: virus-dependent effect of viral load on sensitivity to lethal defection.

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    Héctor Moreno

    Full Text Available BACKGROUND: Lethal mutagenesis is a transition towards virus extinction mediated by enhanced mutation rates during viral genome replication, and it is currently under investigation as a potential new antiviral strategy. Viral load and virus fitness are known to influence virus extinction. Here we examine the effect or the multiplicity of infection (MOI on progeny production of several RNA viruses under enhanced mutagenesis. RESULTS: The effect of the mutagenic base analogue 5-fluorouracil (FU on the replication of the arenavirus lymphocytic choriomeningitis virus (LCMV can result either in inhibition of progeny production and virus extinction in infections carried out at low multiplicity of infection (MOI, or in a moderate titer decrease without extinction at high MOI. The effect of the MOI is similar for LCMV and vesicular stomatitis virus (VSV, but minimal or absent for the picornaviruses foot-and-mouth disease virus (FMDV and encephalomyocarditis virus (EMCV. The increase in mutation frequency and Shannon entropy (mutant spectrum complexity as a result of virus passage in the presence of FU was more accentuated at low MOI for LCMV and VSV, and at high MOI for FMDV and EMCV. We present an extension of the lethal defection model that agrees with the experimental results. CONCLUSIONS: (i Low infecting load favoured the extinction of negative strand viruses, LCMV or VSV, with an increase of mutant spectrum complexity. (ii This behaviour is not observed in RNA positive strand viruses, FMDV or EMCV. (iii The accumulation of defector genomes may underlie the MOI-dependent behaviour. (iv LCMV coinfections are allowed but superinfection is strongly restricted in BHK-21 cells. (v The dissimilar effects of the MOI on the efficiency of mutagenic-based extinction of different RNA viruses can have implications for the design of antiviral protocols based on lethal mutagenesis, presently under development.

  12. Patient Use of Electronic Prescription Refill and Secure Messaging and Its Association With Undetectable HIV Viral Load: A Retrospective Cohort Study

    Science.gov (United States)

    Shimada, Stephanie L; Midboe, Amanda M; Nazi, Kim M; Zhao, Shibei; Wu, Justina; Garvey, Casey M; Houston, Thomas K

    2017-01-01

    Background Electronic personal health records (PHRs) can support patient self-management of chronic conditions. Managing human immunodeficiency virus (HIV) viral load, through taking antiretroviral therapy (ART) is crucial to long term survival of persons with HIV. Many persons with HIV have difficulty adhering to their ART over long periods of time. PHRs contribute to chronic disease self-care and may help persons with HIV remain adherent to ART. Proportionally veterans with HIV are among the most active users of the US Department of Veterans Affairs (VA) PHR, called My HealtheVet. Little is known about whether the use of the PHR is associated with improved HIV outcomes in this population. Objective The objective of this study was to investigate whether there are associations between the use of PHR tools (electronic prescription refill and secure messaging [SM] with providers) and HIV viral load in US veterans. Methods We conducted a retrospective cohort study using data from the VA’s electronic health record (EHR) and the PHR. We identified veterans in VA care from 2009-2012 who had HIV and who used the PHR. We examined which ones had achieved the positive outcome of suppressed HIV viral load, and whether achievement of this outcome was associated with electronic prescription refill or SM. From 18,913 veterans with HIV, there were 3374 who both had a detectable viral load in 2009 and who had had a follow-up viral load test in 2012. To assess relationships between electronic prescription refill and viral control, and SM and viral control, we fit a series of multivariable generalized estimating equation models, accounting for clustering in VA facilities. We adjusted for patient demographic and clinical characteristics associated with portal use. In the initial models, the predictor variables were included in dichotomous format. Subsequently, to evaluate a potential dose-effect, the predictor variables were included as ordinal variables. Results Among our sample

  13. Outcomes from monitoring of patients on antiretroviral therapy in resource-limited settings with viral load, CD4 cell count, or clinical observation alone: a computer simulation model

    DEFF Research Database (Denmark)

    Phillips, Andrew N; Pillay, Deenan; Miners, Alec H;

    2008-01-01

    BACKGROUND: In lower-income countries, WHO recommends a population-based approach to antiretroviral treatment with standardised regimens and clinical decision making based on clinical status and, where available CD4 cell count, rather than viral load. Our aim was to study the potential consequenc...

  14. Factors associated with short-term changes in HIV viral load and CD4+ cell count in antiretroviral-naive individuals

    DEFF Research Database (Denmark)

    Lundgren, Jens

    2014-01-01

    OBJECTIVES: Among antiretroviral therapy (ART)-naive individuals, viral load levels tend to increase and CD4(+) cell counts decline over time. We sought to explore the rate of change and influence of other factors associated with these markers of HIV progression. DESIGN: An observational cohort...

  15. Relationship between viral load and behavioral measures of adherence to antiretroviral therapy in children living with human immunodeficiency virus in Latin America

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    Horacio A. Duarte

    2015-06-01

    Full Text Available Few studies have examined antiretroviral therapy adherence in Latin American children. Standardized behavioral measures were applied to a large cohort of human immunodeficiency virus-infected children in Brazil, Mexico, and Peru to assess adherence to prescribed antiretroviral therapy doses during the three days prior to study visits, assess timing of last missed dose, and evaluate the ability of the adherence measures to predict viral suppression. Time trends in adherence were modeled using a generalized estimating equations approach to account for possible correlations in outcomes measured repeatedly in the same participants. Associations of adherence with human immunodeficiency virus viral load were examined using linear regression. Mean enrollment age of the 380 participants was 5 years; 57.6% had undetectable' viral load ( 0.3. Last time missed any antiretroviral therapy dose was reported as "never" for 52.0% at enrollment, increasing to 60.7% and 65.9% at the 6- and 12-month visits, respectively (p< 0.001 for test of trend. The proportion with undetectable viral load was higher among those who never missed a dose at enrollment and the 12-month visit (p≤ 0.005, but not at the 6-month visit (p= 0.2. While antiretroviral therapy adherence measures utilized in this study showed some association with viral load for these Latin American children, they may not be adequate for reliably identifying non-adherence and consequently children at risk for viral resistance. Other strategies are needed to improve the evaluation of adherence in this population.

  16. 病毒载量检测鉴别诊断HIV早期感染%Application of viral load for differentiating diagnosis of early HIV infection

    Institute of Scientific and Technical Information of China (English)

    黑发欣; 张启云; 孙伟东; 张琴; 叶景荣; 刘海林; 卢红艳

    2008-01-01

    目的 研究病毒载量检测在鉴别诊断HIV早期感染中的应用.方法 对13份HIV抗体检测结果高度提示为早期感染的样本进行病毒载量检测,并对这些个体进行随访和抗体检测以证实其感染状况.结果 13份样本中,有12份病毒载量阳性,随访确定1例HIV抗体阳性婴幼儿感染者,11例窗口期感染者;1例HIV抗体呈阳性的婴幼儿,病毒载量阴性,随访证实未感染.病毒载量检测结果与最终的感染状况相符.结论 通过病毒载量检测能够有效鉴别诊断早期感染中的婴幼儿感染(18个月以内抗体呈阳性)和窗口期感染者.病毒载量检测可以作为HIV感染早期不确定样本的诊断依据.%Objective To study the application of viral load for differentiating diagnosis of early HIV infection. Methods Thirteen indeterminate specimens, which showed early HIV infection of antibody detection, were selected. Viral load of the specimens were detected. People with suspicious infection were followed up and certified infection status through EIA and Western blot. Results Twelve of 13 indeterminate specimens which indicated early HIV infection, had positive viral loads. One antibody-positive infant was confirmed to have been infected by HIV and 11 recent infected (window period) persons were certified during the follow-up. One antibody-positive infant had negative viral load and was certified noninfected per-son during the follow-up. Viral load testing results accorded with HIV infection status. Conclusion Viral load testing can be used to diagnose HIV early infection, including antibody-positive infants (within 18 months) and recent infected persons. Viral load testing could be diagnostic in determinate specimens during early HIV infection.

  17. Impact of acute vivax malaria on the immune system and viral load of HIV-positive subjects

    Institute of Scientific and Technical Information of China (English)

    陈小平; 肖斌权; 施文钧; 徐慧芳; 高凯; 饶纪礼; 张周斌

    2003-01-01

    Objective To explore the mechanisms of malariotherapy for human immunodeficiency virus (HIV)-infected patients and to identify which stage(s) of HIV infection is suitable for the treatment of malariotherapy.Methods Therapeutic acute vivax malaria was induced and terminated after 10 fever episodes in 12 HIV-1-infected subjects: Group 1 (G1) had 5 patients with CD4 T-cell counts500/μl at baseline, Group 2 (G2) had 5 patients with CD4 at 499-200/μl and Group 3 had 2 patients with CD4<200/μl (not included in statistical analysis). Enzyme-Linked-Immuno-Sorbent Assay (ELISA) was used to measure plasma levels of cytokines and soluble activation markers. Flow cytometry was used to measure levels of lymphocyte subsets and phenotypes and CD4 cell apoptosis. Bayer bDNA assay was used to test plasma levels of HIV-1 RNA (viral load). Samples were taken and tested twice before malaria (baselines), three times during malaria and seven times after termination of malaria (at day 10 and 1, 3, 6, 12, 18 and 24 months). Results Levels of plasma tumor necrosis factor-α (TNF-α), soluble TNF-α receptor-2 (sTNF-RII), neopterin (NPT) and soluble IL-2 receptor (sIL-2R) significantly increased during malaria and sharply reduced to baselines post malaria in all groups. Stronger responses of the aforementioned factors were seen in G2 than in G1 during malaria (P=0.081, 0.001, 0.013, 0.020). CD4 count and percentage; CD4/CD8 ratio and CD25+ and CD4+CD25+ percentages increased but HLA DR+ percentage decreased either during or post malaria in G2. Most G2 patients experienced sustained increase but most G1 patients underwent natural history decline of CD4 counts and percentages during 2-year follow-up. Percentage of apoptotic CD4 cells decreased post malaria in all groups. G3 patients had weaker immune responses, however, one advanced AIDS patient in this group experienced clinical improvement after malariotherapy. Most of the 12 patients experienced increase of HIV viral load during

  18. Does chronic alcohol use by HIV-infected patients on d4T/3TC/NVP drug regimen effect the HIV viral load and what is the therapeutic window of the drugs, CD4+ count and WBC count in patients with high viral load during the 9 months period of follow up?

    Directory of Open Access Journals (Sweden)

    Godfrey S. Bbosa

    2013-10-01

    Full Text Available The study investigated the effects of chronic alcohol use on HIV viral load in HIV-infected patients on d4T/3TC/NVP drug regimen during 9 months follow up period. It also determined plasma drug concentrations of d4T, 3TC and NVP; CD4+ and WBC counts for patients with high HIV viral load. A case-control study using repeated measures with serial measurements was used. A total of 41 patients (20 alcohol group and 21 control group were screened for alcohol use using WHO AUDIT tool and chronic alcohol use biomarkers. Blood sampling was done at 3 month intervals for a period of 9 months. HIV viral load was determined using Roche Amplicor HIV-1 monitor test, version 1.5 (Amplicor. The d4T, 3TC and NVP concentrations were determined by Shimadzu Class-VPTM HPLC Chromatography data system version 6.1. The CD4+ cell count was determined using FACSCalibur flow cytometer. The WBC was determined using automated hematological Coulter CBC-5 Hematology Analyzer system. Results show that % patients with HIV viral load ≥400 copies/ml in control group was highest (23.8%, n=5 at 3 month while in chronic alcohol use group, it was at 0 month (35%, n=7 for both WHO AUDIT tool and chronic alcohol-use biomarkers groups. Generally patients with high viral load ≥400 copies/ml was observed in chronic alcohol use as compared to control group in both WHO AUDIT tool and biomarkers group despite of patients having high steady state d4T, 3TC and NVP plasma drug concentrations in circulation that is available to suppress HIV virus. The high viral load could be associated with the emergence of resistance of the HIV virus and these patients generally had a low CD4+ cell count. Some of these patients had no detectable d4T plasma drug concentrations in circulation and most of them with high viral load had sub-therapeutic NVP plasma drug concentrations in their blood circulation. Chronic ethanol use by HIV-infected patients on d4T/3TC/NVP drug regimen increased HIV viral load and

  19. Cigarette smoking is associated with high HIV viral load among adults presenting for antiretroviral therapy in Vietnam

    Science.gov (United States)

    Pollack, Todd M.; Duong, Hao T.; Pham, Thuy T.; Do, Cuong D.; Colby, Donn

    2017-01-01

    High HIV viral load (VL >100,000 cp/ml) is associated with increased HIV transmission risk, faster progression to AIDS, and reduced response to some antiretroviral regimens. To better understand factors associated with high VL, we examined characteristics of patients presenting for treatment in Hanoi, Vietnam. We examined baseline data from the Viral Load Monitoring in Vietnam Study, a randomized controlled trial of routine VL monitoring in a population starting antiretroviral therapy (ART) at a clinic in Hanoi. Patients with prior treatment failure or ART resistance were excluded. Characteristics examined included demographics, clinical and laboratory data, and substance use. Logistic regression was used to calculate crude and adjusted odds ratios (aOR) and 95% confidence intervals (95% CI). Out of 636 patients, 62.7% were male, 72.9% were ≥30 years old, and 28.3% had a history of drug injection. Median CD4 was 132 cells/mm3, and 34.9% were clinical stage IV. Active cigarette smoking was reported by 36.3% with 14.0% smoking >10 cigarettes per day. Alcohol consumption was reported by 20.1% with 6.1% having ≥5 drinks per event. Overall 53.0% had a VL >100,000 cp/ml. Male gender, low body weight, low CD4 count, prior TB, and cigarette smoking were associated with high VL. Those who smoked 1–10 cigarettes per day were more likely to have high VL (aOR = 1.99, 95% CI = 1.15–3.45), while the smaller number of patients who smoked >10 cigarettes per day had a non-significant trend toward higher VL (aOR = 1.41, 95% CI = 0.75–2.66). Alcohol consumption was not significantly associated with high VL. Tobacco use is increasingly recognized as a contributor to premature morbidity and mortality among HIV-infected patients. In our study, cigarette smoking in the last 30 days was associated with a 1.5 to 2-fold higher odds of having an HIV VL >100,000 cp/ml among patients presenting for ART. These findings provide further evidence of the negative effects of tobacco use

  20. Frequent Hypermethylation of RASSF1A, TSLC1, High Viral Load of Epstein-Barr Virus DNA in Nasopharyngeal Carcinoma, Matched Tumor-Adjacent Tissues

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    Liang Zhou

    2005-09-01

    Full Text Available We examined the promoter hypermethylation of tumorsuppressor genes RASSF1A, TSLC1, quantitated EBV DNA load in nasopharyngeal carcinoma (NPC tissues (T tissues, matched tumor-adjacent tissues outside 0.5 cm (P tissues, outside 1.0 cm (Z tissues to evaluate the role of promoter hypermethylation of RASSF1A, TSLC1 as well as viral load in the pathogenesis of NPC. Methylation-specific polymerase chain reaction (PCR for RASSF1A, TSLC1, quantitative real-time PCR analysis of EBV DNA were performed on matched T, P, Z tissues (n = 28 as well as chronic nasopharyngitis tissues (n = 8. Hypermethylated RASSF1A was frequently detected in the T (82%, P tissues (75%, but less frequently in Z tissues (46%. The average quantities of EBV DNA (copies/μg DNA in matched T, P, Z tissues were 673,000, 90,000, 7000. The differences of promoter hypermethylation of RASSF1A, EBV viral load among T, P, Z tissues were statistically significant, with more frequent methylation, higher viral load detected when tissues examined were nearer to the NPC tissues. Our results suggest that aberrant hypermethylation of RASSF1A, high EBV load might be important events in NPC pathogenesis, they may be useful molecular diagnostic markers for this cancer.

  1. Association with Spontaneous Hepatitis C Viral Clearance and Genetic Differentiation of IL28B/IFNL4 Haplotypes in Populations from Mexico

    Science.gov (United States)

    Gonzalez-Aldaco, Karina; Rebello Pinho, João R.; Roman, Sonia; Gleyzer, Ketti; Fierro, Nora A.; Oyakawa, Leticia; Ramos-Lopez, Omar; Ferraz Santana, Rubia A.; Sitnik, Roberta; Panduro, Arturo

    2016-01-01

    Aim To analyze the genetic heterogeneity of the Amerindian and admixed population (Mestizos) based on the IL28B (rs12979860, rs8099917) and IFNL4 (rs368234815) haplotypes, and their association with spontaneous clearance (SC) and liver damage in patients with hepatitis C infection from West Mexico. Methods A total of 711 subjects from West Mexico (181 Amerindians and 530 Mestizos) were studied for the prevalence of IL28B (rs12979860C/T, rs8099917G/T) and IFNL4 (rs368234815∆G/TT) genotypes. A case-control study was performed in 234 treatment-naïve HCV Mestizos (149 chronic hepatitis C and 85 with SC) for the association of haplotypes with SC and liver damage. A real-time PCR assay was used for genotyping, and transitional elastography staged liver damage. Results Significant Fst-values indicated differentiation between the studied populations. The frequencies of the protective C, T, TT alleles were significantly lower in the Amerindians than in Mestizos (p<0.05). The r2 measure of linkage disequilibrium was significant for all variants and the T/G/ΔG risk haplotype predominated in Amerindians and secondly in Mestizos. The protective C/T/TT haplotype was associated with SC (OR = 0.46, 95% IC 0.22–0.95, p = 0.03) and less liver damage (OR = 0.32, 95% IC 0.10–0.97, p = 0.04) in chronic patients. The Structure software analysis demonstrated no significant differences in ancestry among SC and chronic patients. Conclusions West Mexico´s population is genetically heterogeneous at the IL28B/IFNL4 polymorphisms. The T/G/ΔG high-risk haplotype predominated in Amerindians and the beneficial alternative haplotype in Mestizos. The C/T/TT haplotype was associated with SC and less liver damage in chronically infected Mestizo patients. PMID:26741362

  2. Characterization of viral loads, strain and state of equine herpesvirus-1 using real-time PCR in horses following natural exposure at a racetrack in California.

    Science.gov (United States)

    Pusterla, Nicola; Wilson, W David; Mapes, Samantha; Finno, Carrie; Isbell, Diane; Arthur, Rick M; Ferraro, Gregory L

    2009-02-01

    The objective of this study was to determine viral loads, strain (neuropathogenic versus non-neuropathogenic) and state (lytic, non-replicating, latent) of equine herpesvirus-1 (EHV-1) by real-time polymerase chain reaction (PCR) in the blood and nasopharyngeal secretions of adult horses following natural exposure. The index case, a 4-year-old Thoroughbred gelding with confirmed EHV-1 myeloencephalopathy, as well as potentially exposed horses, were sampled over a period of 3 weeks. The study population comprised of 39 adult Thoroughbred horses and 35 adult "pony" and outrider horses of various breeds housed at a racetrack in Northern California. Blood samples and nasopharyngeal secretions (NPS) from all horses were tested on several occasions for EHV-1 DNA viral loads, targeting the glycoprotein B (gB) gene, viral strain, targeting the ORF 30 gene, and transcriptional activity of EHV-1, targeting the gB gene and latency-associated transcripts (LATs). Viral loads and transcriptional activity of the gB gene declined rapidly in the index case following antiviral treatment. The prevalence of EHV-1 infection in NPS determined by PCR slowly decreased over the 22 day study period from 25% to 14%. The initial surveillance showed multiple clusters of exposure, one associated with the index case and two related to horses that had recently returned from a different racetrack. Viral strain differentiation showed that only two horses (the index case and a neighboring horse) were infected with only a neuropathogenic strain, while all other horses were infected with either a non-neuropathogenic strain or were dually infected with both neuropathogenic and non-neuropathogenic strains. In most cases, the virus was present in either a lytic or a non-replicating form, while latent virus was found in blood and NPS much less frequently. The molecular approach used in this study showed promise for assessing the risk of exposing other horses to EHV-1 and for studying viral kinetics in

  3. Liver stiffness measurement and biochemical markers in Senegalese chronic hepatitis B patients with normal ALT and high viral load.

    Directory of Open Access Journals (Sweden)

    Papa Saliou Mbaye

    Full Text Available BACKGROUND AND AIMS: Despite the high prevalence of chronic hepatitis B (CHB in Africa, few studies have been performed among African patients. We sought to evaluate liver stiffness measurement by FibroScan® (LSM and two biochemical scores (FibroTest®, Fibrometer® to diagnose liver fibrosis in Senegalese CHB patients with HBV plasma DNA load ≥3.2 log(10 IU/mL and normal alanine aminotransferase (ALT values. METHODS: LSM and liver fibrosis biochemical markers were performed on 225 consecutive HBV infected Senegalese patients with high viral load. Patients with an LSM range between 7 and 13 kPa underwent liver biopsy (LB. Two experienced liver pathologists performed histological grading using Metavir and Ishak scoring. RESULTS: 225 patients were evaluated (84% male and LB was performed in 69 patients, showing F2 and F3 fibrosis in 17% and 10% respectively. In these patients with a 7-13 kPa range of LSM, accuracy for diagnosis of significant fibrosis according to LB was unsatisfactory for all non-invasive markers with AUROCs below 0.70. For patients with LSM values below 7 kPa, FibroTest® (FT, and Fibrometer® (FM using the cut-offs recommended by the test promoters suggested a fibrosis in 18% of cases for FT (8% severe fibrosis and 8% for FM. For patients with LSM values greater than 13 kPa, FT, FM suggested a possible fibrosis in 73% and 70%, respectively. CONCLUSION: In highly replicative HBV-infected African patients with normal ALT and LSM value below 13 kPa, FibroScan®, FibroTest® or Fibrometer® were unsuitable to predict the histological liver status of fibrosis.

  4. Systematic review and meta-analysis of hepatitis C virus infection and HIV viral load: new insights into epidemiologic synergy

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    Nicholas Petersdorf

    2016-09-01

    Full Text Available Introduction: Hepatitis C virus (HCV and HIV infection frequently co-occur due to shared transmission routes. Co-infection is associated with higher HCV viral load (VL, but less is known about the effect of HCV infection on HIV VL and risk of onward transmission. Methods: We undertook a systematic review comparing 1 HIV VL among ART-naïve, HCV co-infected individuals versus HIV mono-infected individuals and 2 HIV VL among treated versus untreated HCV co-infected individuals. We performed a random-effects meta-analysis and quantified heterogeneity using the I2 statistic. We followed Cochrane Collaboration guidelines in conducting our review and PRISMA guidelines in reporting results. Results and discussion: We screened 3925 articles and identified 17 relevant publications. A meta-analysis found no evidence of increased HIV VL associated with HCV co-infection or between HIV VL and HCV treatment with pegylated interferon-alpha-2a/b and ribavirin. Conclusions: This finding is in contrast to the substantial increases in HIV VL observed with several other systemic infections. It presents opportunities to elucidate the biological pathways that underpin epidemiological synergy in HIV co-infections and may enable prediction of which co-infections are most important to epidemic control.

  5. Systematic review and meta-analysis of hepatitis C virus infection and HIV viral load: new insights into epidemiologic synergy

    Science.gov (United States)

    Petersdorf, Nicholas; Ross, Jennifer M; Weiss, Helen A; Barnabas, Ruanne V; Wasserheit, Judith N

    2016-01-01

    Introduction Hepatitis C virus (HCV) and HIV infection frequently co-occur due to shared transmission routes. Co-infection is associated with higher HCV viral load (VL), but less is known about the effect of HCV infection on HIV VL and risk of onward transmission. Methods We undertook a systematic review comparing 1) HIV VL among ART-naïve, HCV co-infected individuals versus HIV mono-infected individuals and 2) HIV VL among treated versus untreated HCV co-infected individuals. We performed a random-effects meta-analysis and quantified heterogeneity using the I2 statistic. We followed Cochrane Collaboration guidelines in conducting our review and PRISMA guidelines in reporting results. Results and discussion We screened 3925 articles and identified 17 relevant publications. A meta-analysis found no evidence of increased HIV VL associated with HCV co-infection or between HIV VL and HCV treatment with pegylated interferon-alpha-2a/b and ribavirin. Conclusions This finding is in contrast to the substantial increases in HIV VL observed with several other systemic infections. It presents opportunities to elucidate the biological pathways that underpin epidemiological synergy in HIV co-infections and may enable prediction of which co-infections are most important to epidemic control. PMID:27649908

  6. Use of Dried Plasma Spots for HIV-1 Viral Load Determination and Drug Resistance Genotyping in Mexican Patients

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    Juan Pablo Rodriguez-Auad

    2015-01-01

    Full Text Available Monitoring antiretroviral therapy using measurements of viral load (VL and the genotyping of resistance mutations is not routinely performed in low- to middle-income countries because of the high costs of the commercial assays that are used. The analysis of dried plasma spot (DPS samples on filter paper may represent an alternative for resource-limited settings. Therefore, we evaluated the usefulness of analyzing DPS samples to determine VL and identify drug resistance mutations (DRM in a group of HIV-1 patients. The VL was measured from 22 paired plasma and DPS samples. In these samples, the average VL was 4.7 log10 copies/mL in liquid plasma and 4.1 log10 copies/mL in DPS, with a correlation coefficient of R = 0.83. A 1.1 kb fragment of HIV pol could be amplified in 14/22 (63.6% of the DPS samples and the same value was amplified in plasma samples. A collection of ten paired DPS and liquid plasma samples was evaluated for the presence of DRM; an excellent correlation was found in the identification of DRM between the paired samples. All HIV-1 pol sequences that were obtained corresponded to HIV subtype B. The analysis of DPS samples offers an attractive alternative for monitoring ARV therapy in resource-limited settings.

  7. Use of Dried Plasma Spots for HIV-1 Viral Load Determination and Drug Resistance Genotyping in Mexican Patients

    Science.gov (United States)

    Rodriguez-Auad, Juan Pablo; Rojas-Montes, Othon; Maldonado-Rodriguez, Angelica; Alvarez-Muñoz, Ma. Teresa; Muñoz, Onofre; Torres-Ibarra, Rocio; Vazquez-Rosales, Guillermo

    2015-01-01

    Monitoring antiretroviral therapy using measurements of viral load (VL) and the genotyping of resistance mutations is not routinely performed in low- to middle-income countries because of the high costs of the commercial assays that are used. The analysis of dried plasma spot (DPS) samples on filter paper may represent an alternative for resource-limited settings. Therefore, we evaluated the usefulness of analyzing DPS samples to determine VL and identify drug resistance mutations (DRM) in a group of HIV-1 patients. The VL was measured from 22 paired plasma and DPS samples. In these samples, the average VL was 4.7 log10 copies/mL in liquid plasma and 4.1 log10 copies/mL in DPS, with a correlation coefficient of R = 0.83. A 1.1 kb fragment of HIV pol could be amplified in 14/22 (63.6%) of the DPS samples and the same value was amplified in plasma samples. A collection of ten paired DPS and liquid plasma samples was evaluated for the presence of DRM; an excellent correlation was found in the identification of DRM between the paired samples. All HIV-1 pol sequences that were obtained corresponded to HIV subtype B. The analysis of DPS samples offers an attractive alternative for monitoring ARV therapy in resource-limited settings. PMID:26779533

  8. Use of plasma human herpesvirus-8 viral load measurement: evaluation of practice in three UK HIV treatment centres.

    Science.gov (United States)

    Nugent, D B; Webster, D; Mabayoje, D; Chung, E; El Bouzidi, K; O'Sullivan, A; Ainsworth, J; Miller, R F

    2017-02-01

    A retrospective audit of plasma human herpesvirus-8 (HHV-8) viral load testing was performed in three HIV treatment centres over 24 months. Reasons for testing (360 tests) were: symptoms of systemic inflammatory response syndrome (SIRS) (fever, lymphadenopathy and raised inflammatory markers); monitoring in known HHV-8 pathology other than Kaposi sarcoma (KS); investigation of known/suspected KS, and other/no reason. Of patients with multicentric Castleman disease (MCD), 14/16 (88%) had detectable plasma HHV-8, as did 27/45 (60%) with biopsy proven or clinically confirmed KS, and 6/19 (32%) with lymphoma. Neither of the two patients with MCD and no detectable HHV-8 had SIRS symptoms at the time of the test. There was wide variation between centres in the indications prompting HHV-8 testing, with a more conservative approach resulting in a higher proportion of positive results. Measuring plasma HHV-8 in the absence of SIRS symptoms, established HHV-8 disease monitoring, or confirmed/suspected KS is unlikely to yield detectable HHV-8 thus allowing potential cost savings.

  9. Co-financing for viral load monitoring during the course of antiretroviral therapy among patients with HIV/AIDS in Vietnam: A contingent valuation survey

    Science.gov (United States)

    Tran, Bach Xuan; Phan, Huong Thi Thu; Le, Huong Thi; Nguyen, Hinh Duc; Tran, Tho Dinh; Do, Cuong Duy; Nguyen, Cuong Manh; Thuc, Vu Thi Minh; Latkin, Carl; Zhang, Melvyn W. B.; Ho, Roger C. M.

    2017-01-01

    Background Viral load testing is considered the gold standard for monitoring HIV treatment; however, given its high cost, some patients cannot afford viral load testing if this testing is not subsidized. Since foreign aid for HIV/AIDS in Vietnam is rapidly decreasing, we sought to assess willingness to pay (WTP) for viral load and CD4 cell count tests among HIV-positive patients, and identified factors that might inform future co-payment schemes. Methods A multi-site cross-sectional survey was conducted with 1133 HIV-positive patients on antiretroviral therapy (ART) in Hanoi and Nam Dinh. Patients’ health insurance coverage, quality of life, and history of illicit drug use were assessed. A contingent valuation approach was employed to measure patients’ WTP for CD4 cell count and viral load testing. Results HIV-positive patients receiving ART at provincial sites reported more difficulty obtaining health insurance (HI) and had the overall the poorest quality of life. Most patients (90.9%) were willing to pay for CD4 cell count testing; here, the mean WTP was valued at US$8.2 (95%CI = 7.6–8.8 US$) per test. Most patients (87.3%) were also willing to pay for viral load testing; here, mean WTP was valued at US$18.6 (95%CI = 16.3–20.9 US$) per test. High income, high education level, and hospitalization were positively associated with WTP, while co-morbidity with psychiatric symptoms and trouble paying for health insurance were both negatively related to WTP. Conclusions These findings raise concerns that HIV-positive patients in Vietnam might have low WTP for CD4 cell count and viral load testing. This means that without foreign financial subsidies, many of these patients would likely go without these important tests. Treating psychiatric co-morbidities, promoting healthcare services utilization, and removing barriers to accessing health insurance may increase WTP for monitoring of HIV/AIDS treatment among HIV+-positive Vietnamese patients. PMID:28199405

  10. PLGA-PEG Nanoparticles Coated with Anti-CD45RO and Loaded with HDAC Plus Protease Inhibitors Activate Latent HIV and Inhibit Viral Spread

    Science.gov (United States)

    Tang, Xiaolong; Liang, Yong; Liu, Xinkuang; Zhou, Shuping; Liu, Liang; Zhang, Fujina; Xie, Chunmei; Cai, Shuyu; Wei, Jia; Zhu, Yongqiang; Hou, Wei

    2015-10-01

    Activating HIV-1 proviruses in latent reservoirs combined with inhibiting viral spread might be an effective anti-HIV therapeutic strategy. Active specific delivery of therapeutic drugs into cells harboring latent HIV, without the use of viral vectors, is a critical challenge to this objective. In this study, nanoparticles of poly(lactic-co-glycolic acid)-polyethylene glycol diblock copolymers conjugated with anti-CD45RO antibody and loaded with the histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA) and/or protease inhibitor nelfinavir (Nel) were tested for activity against latent virus in vitro. Nanoparticles loaded with SAHA, Nel, and SAHA + Nel were characterized in terms of size, surface morphology, zeta potential, entrapment efficiency, drug release, and toxicity to ACH-2 cells. We show that SAHA- and SAHA + Nel-loaded nanoparticles can target latently infected CD4+ T-cells and stimulate virus production. Moreover, nanoparticles loaded with SAHA + NEL were capable of both activating latent virus and inhibiting viral spread. Taken together, these data demonstrate the potential of this novel reagent for targeting and eliminating latent HIV reservoirs.

  11. Generation of dried tube specimen for HIV-1 viral load proficiency test panels: a cost-effective alternative for external quality assessment programs.

    Science.gov (United States)

    Ramos, Artur; Nguyen, Shon; Garcia, Albert; Subbarao, Shambavi; Nkengasong, John N; Ellenberger, Dennis

    2013-03-01

    Participation in external quality assessment programs is critical to ensure quality clinical laboratory testing. Commercially available proficiency test panels for HIV-1 virus load testing that are used commonly in external quality assessment programs remain a financial obstacle to resource-limited countries. Maintaining cold-chain transportation largely contributes to the cost of traditional liquid proficiency test panels. Therefore, we developed and evaluated a proficiency test panel using dried tube specimens that can be shipped and stored at ambient temperature. This dried tube specimens panel consisted of 20 μl aliquots of a HIV-1 stock that were added to 2 ml tubes and left uncapped for drying, as a preservation method. The stability of dried tube specimens at concentrations ranging from 10² to 10⁶·⁵ RNA copies/ml was tested at different temperatures over time, showing no viral load reduction at 37 °C and a decrease in viral load smaller than 0.5 Log₁₀ at 45 °C for up to eight weeks when compared to initial results. Eight cycles of freezing-thawing had no effect on the stability of the dried tube specimens. Comparable viral load results were observed when dried tube specimen panels were tested on Roche CAPTAQ, Abbott m2000, and Biomerieux easyMAG viral load systems. Preliminary test results of dried proficiency test panels shipped to four African countries at ambient temperature demonstrated a low inter assay variation (SD range: 0.29-0.41 Log₁₀ RNA copies/ml). These results indicated that HIV-1 proficiency test panels generated by this methodology might be an acceptable alternative for laboratories in resource-limited countries to participate in external quality assessment programs.

  12. Some novel insights on HPV16 related cervical cancer pathogenesis based on analyses of LCR methylation, viral load, E7 and E2/E4 expressions.

    Directory of Open Access Journals (Sweden)

    Damayanti Das Ghosh

    Full Text Available This study was undertaken to decipher the interdependent roles of (i methylation within E2 binding site I and II (E2BS-I/II and replication origin (nt 7862 in the long control region (LCR, (ii expression of viral oncogene E7, (iii expression of the transcript (E7-E1/E4 that encodes E2 repressor protein and (iv viral load, in human papillomavirus 16 (HPV16 related cervical cancer (CaCx pathogenesis. The results revealed over-representation (p<0.001 of methylation at nucleotide 58 of E2BS-I among E2-intact CaCx cases compared to E2-disrupted cases. Bisulphite sequencing of LCR revealed overrepresentation of methylation at nucleotide 58 or other CpGs in E2BS-I/II, among E2-intact cases than E2-disrupted cases and lack of methylation at replication origin in case of both. The viral transcript (E7-E1/E4 that produces the repressor E2 was analyzed by APOT (amplification of papillomavirus oncogenic transcript-coupled-quantitative-RT-PCR (of E7 and E4 genes to distinguish episomal (pure or concomitant with integrated from purely integrated viral genomes based on the ratio, E7 C(T/E4 C(T. Relative quantification based on comparative C(T (threshold cycle method revealed 75.087 folds higher E7 mRNA expression in episomal cases over purely integrated cases. Viral load and E2 gene copy numbers were negatively correlated with E7 C(T (p = 0.007 and E2 C(T (p<0.0001, respectively, each normalized with ACTB C(T, among episomal cases only. The k-means clustering analysis considering E7 C(T from APOT-coupled-quantitative-RT-PCR assay, in conjunction with viral load, revealed immense heterogeneity among the HPV16 positive CaCx cases portraying integrated viral genomes. The findings provide novel insights into HPV16 related CaCx pathogenesis and highlight that CaCx cases that harbour episomal HPV16 genomes with intact E2 are likely to be distinct biologically, from the purely integrated viral genomes in terms of host genes and/or pathways involved in cervical

  13. Switching tenofovir/emtricitabine plus lopinavir/r to raltegravir plus Darunavir/r in patients with suppressed viral load did not result in improvement of renal function but could sustain viral suppression: a randomized multicenter trial.

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    Takeshi Nishijima

    Full Text Available BACKGROUND: Whether tenofovir nephrotoxicity is reversible after its withdrawal is unknown. Furthermore, there are no data on the viral efficacy of raltegravir (RAL plus ritonavir-boosted Darunavir (DRV/r in patients with suppressed viral load. METHODS: This multicenter, randomized trial compared renal function and viral efficacy in patients with suppressed viral load treated with RAL+DRV/r and ritonavir-boosted lopinavir (LPV/r plus tenofovir/emtricitabine (TVD, who had been previously on LPV/r+TVD. The primary endpoint was the proportion of patients with >10% improvement in estimated glomerular filtration rate (eGFR at 48 weeks calculated with Cockcroft-Gault equation. RESULTS: 58 randomized and treatment-exposed patients were analyzed (28 on RAL+DRV/r and 30 on LPV/r+TVD. Greater than 10% improvement in eGFR was noted in 6 (25% out of 24 with RAL+DRV/r and 3 (11% of 28 with LPV/r+TVD, and the difference was not statistically significant (p=0.272, 95% CI -0.067 to 0.354. Sensitivity analyses using three other equations for eGFR showed the same results. Urinary β2 microglobulin, a sensitive marker of tenofovir tubulopathy, significantly improved with RAL+DRV/r than with LPV/r+TVD (-271 versus -64 µg/gCr, p=0.026. Per protocol analysis showed that the HIV-RNA was 10% improvement in renal function among those with relatively preserved eGFR. However, the switch improved urinary β2 microglobulin, suggesting that discontinuation of TDF might be beneficial in the long-term. RAL+DRV/r showed favorable viral efficacy in patients with suppressed viral load. TRIAL REGISTRATION: ClinicalTrials.gov NCT01294761 http://clinicaltrials.gov/ct2/show/NCT01294761?term=SPARE&rank=2, Umin Clinical Trials Registry UMIN000005116 http://upload.umin.ac.jp/cgi-open-bin/ctr/ctr.cgi?function=brows&action=brows&type=summary&recptno=R000006083&language=J.

  14. Antibody-Mediated Clearance of Alphavirus Infection from Neurons

    Science.gov (United States)

    Levine, Beth; Hardwick, J. Marie; Trapp, Bruce D.; Crawford, Thomas O.; Bollinger, Robert C.; Griffin, Diane E.

    1991-11-01

    Humoral immunity is important for protection against viral infection and neutralization of extracellular virus, but clearance of virus from infected tissues is thought to be mediated solely by cellular immunity. However, in a SCID mouse model of persistent alphavirus encephalomyelitis, adoptive transfer of hyperimmune serum resulted in clearance of infectious virus and viral RNA from the nervous system, whereas adoptive transfer of sensitized T lymphocytes had no effect on viral replication. Three monoclonal antibodies to two different epitopes on the E2 envelope glycoprotein mediated viral clearance. Treatment of alphavirus-infected primary cultured rat neurons with these monoclonal antibodies to E2 resulted in decreased viral protein synthesis, followed by gradual termination of mature infectious virion production. Thus, antibody can mediate clearance of alphavirus infection from neurons by restricting viral gene expression.

  15. Quantitative analysis of viral load per haploid genome revealed the different biological features of Merkel cell polyomavirus infection in skin tumor.

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    Satoshi Ota

    Full Text Available Merkel cell polyomavirus (MCPyV has recently been identified in Merkel cell carcinoma (MCC, an aggressive cancer that occurs in sun-exposed skin. Conventional technologies, such as polymerase chain reaction (PCR and immunohistochemistry, have produced conflicting results for MCPyV infections in non-MCC tumors. Therefore, we performed quantitative analyses of the MCPyV copy number in various skin tumor tissues, including MCC (n = 9 and other sun exposure-related skin tumors (basal cell carcinoma [BCC, n = 45], actinic keratosis [AK, n = 52], Bowen's disease [n = 34], seborrheic keratosis [n = 5], primary cutaneous anaplastic large-cell lymphoma [n = 5], malignant melanoma [n = 5], and melanocytic nevus [n = 6]. In a conventional PCR analysis, MCPyV DNA was detected in MCC (9 cases; 100%, BCC (1 case; 2%, and AK (3 cases; 6%. We then used digital PCR technology to estimate the absolute viral copy number per haploid human genome in these tissues. The viral copy number per haploid genome was estimated to be around 1 in most MCC tissues, and there were marked differences between the MCC (0.119-42.8 and AK (0.02-0.07 groups. PCR-positive BCC tissue showed a similar viral load as MCC tissue (0.662. Immunohistochemistry with a monoclonal antibody against the MCPyV T antigen (CM2B4 demonstrated positive nuclear localization in most of the high-viral-load tumor groups (8 of 9 MCC and 1 BCC, but not in the low-viral-load or PCR-negative tumor groups. These results demonstrated that MCPyV infection is possibly involved in a minority of sun-exposed skin tumors, including BCC and AK, and that these tumors display different modes of infection.

  16. The effect of N-acetylcysteine supplementation upon viral load, CD4, CD8, total lymphocyte count and hematocrit in individuals undergoing antiretroviral treatment.

    Science.gov (United States)

    Spada, Celso; Treitinger, Arício; Reis, Marcellus; Masokawa, Ivete Y; Verdi, Júlio C; Luiz, Magali C; Silveira, Mariete V S; Michelon, Cleonice M; Avila-Junior, Silvio; Gil, lone D O; Ostrowskyl, Stephanie

    2002-05-01

    Individuals infected with the human immunodeficiency virus (HIV-1) present with decreased CD4, a progressive increase in viral load, compromised cell immune defense, and hematologic alterations. The aim of this study was to assess the serum viral load, CD4, CD8, lymphocyte count and hematocrit at the beginning of antiretroviral therapy in individuals who were supplemented with N-acetylcysteine (NAC). Twenty volunteers participated in this double-blind, placebo-controlled 180-day study. Ten participants received 600 mg of NAC per day (NAC group) and the other ten serving as a control group received placebo. The above mentioned parameters were determined before treatment, and after 60, 120 and 180 days. In NAC-treated patients hematocrit remained stable and an increase in CD4 cell count took place earlier than that in the control group.

  17. Syphilis and HIV-1 co-infection: influence on CD4 T cell count, HIV-1 viral load and treatment response

    DEFF Research Database (Denmark)

    Kofoed, Kristian; Gerstoft, Jan; Mathiesen, Lars Reinhardt;

    2006-01-01

    OBJECTIVES: To assess the effect of human immunodeficiency virus (HIV)-1 and syphilis coinfection on HIV-ribonucleic acid (RNA) viral load, CD4 cell count, and the response in rapid plasmin reagin (RPR) to treatment of the syphilis infection. STUDY DESIGN: Cases of syphilis diagnosed during 1 yea...... treated with doxycycline were the same. CONCLUSION: Syphilis was associated with a decrease in CD4 cell counts and an increase in HIV-RNA levels that both improved after treatment of syphilis....

  18. Clinical application of real time-polymerase chain reaction in determining cytomegalovirus viral DNA load in renal transplant recipients

    Institute of Scientific and Technical Information of China (English)

    ZHANG Chuan-bao; LAI Hui-ying; XU Hong-tao; WANG Da-guang; XIAO Fei

    2012-01-01

    Background Cytomegalovirus (CMV) remains a significant clinical problem among immunosuppressed renal transplant patients.Quantitative PCR assays have become the most common methods in the determination of CMV infections in transplant patients.This study was to determine the relationship between CMV infection and the acute rejection of the transplanted kidney.Methods Plasma samples from 77 renal transplant patients that were pre-transplant negative for CMV infection were tested using real-time quantitative PCR and CMV gene-specific primers.The detected viral loads were retrospectively compared with the acute rejection rate and the chronic or mild rejection rates of the renal transplant.Results CMV-DNA was detected in 29 of 77 recipients,yielding a positive rate of detection of 37.7% for this procedure.Twelve of the 21 recipients (57.1%) who suffered acute rejection had positive CMV-DNA.Among the 56 recipients suffered from chronic or mild rejection,17 (30.4%) had positive CMV-DNA plasma.Moreover,of the 29 recipients who had detectable CMV-DNA after transplant,12 (41.4%) suffered from acute rejection; of the 48 recipients with undetectable CMV-DNA,only nine (18.8%) developed acute rejection.Post-transplant patients with acute rejection had a higher rate (57.1% vs.30.4%,P=0.03) of post-transplant CMV infection than those with chronic or mild rejection.Conclusion CMV infection is a risk factor of acute renal transplant rejection and CMV infection should be prevented and treated in renal transplant recipients.Chin Med J 2012; 125(19):3575-3577

  19. Comparison of EBV DNA viral load in whole blood, plasma, B-cells and B-cell culture supernatant.

    Science.gov (United States)

    Ouedraogo, David Eric; Bollore, Karine; Viljoen, Johannes; Foulongne, Vincent; Reynes, Jacques; Cartron, Guillaume; Vendrell, Jean-Pierre; Van de Perre, Philippe; Tuaillon, Edouard

    2014-05-01

    Epstein-Barr virus (EBV) genome quantitation in whole blood is used widely for therapeutic monitoring of EBV-associated disorders in immunosuppressed individuals and in patients with EBV-associated lymphoma. However, the most appropriate biological material to be used for EBV DNA quantitation remains a subject of debate. This study compare the detection rate and levels of EBV DNA from whole blood, plasma, enriched B-cells, and B-cell short-term culture supernatant using quantitative real-time PCR. Samples were collected from 33 subjects with either HIV infection or B-cell lymphoma. Overall, EBV DNA was detected in 100% of enriched B-cell samples, in 82% of B-cell culture supernatants, in 57% of plasma, and 42% of whole blood samples. A significant correlation for EBV viral load was found between enriched B-cell and B-cell culture supernatant material (ρ = 0.92; P cells (ρ = -0.02; P = 0.89), whole blood and plasma (ρ = 0.24; P = 0.24), or enriched B-cells and plasma (ρ = 0.08; P = 0.77). Testing of enriched B-cells appeared to be the most sensitive method for detection of EBV DNA as well as for exploration of the cellular reservoir. Quantitation of EBV DNA in plasma and B-cell culture supernatant may be of interest to assess EBV reactivation dynamics and response to treatment as well as to decipher EBV host-pathogen interactions in various clinical scenarios.

  20. A cluster randomized trial of routine HIV-1 viral load monitoring in Zambia: study design, implementation, and baseline cohort characteristics.

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    John R Koethe

    Full Text Available BACKGROUND: The benefit of routine HIV-1 viral load (VL monitoring of patients on antiretroviral therapy (ART in resource-constrained settings is uncertain because of the high costs associated with the test and the limited treatment options. We designed a cluster randomized controlled trial to compare the use of routine VL testing at ART-initiation and at 3, 6, 12, and 18 months, versus our local standard of care (which uses immunological and clinical criteria to diagnose treatment failure, with discretionary VL testing when the two do not agree. METHODOLOGY: Dedicated study personnel were integrated into public-sector ART clinics. We collected participant information in a dedicated research database. Twelve ART clinics in Lusaka, Zambia constituted the units of randomization. Study clinics were stratified into pairs according to matching criteria (historical mortality rate, size, and duration of operation to limit the effect of clustering, and independently randomized to the intervention and control arms. The study was powered to detect a 36% reduction in mortality at 18 months. PRINCIPAL FINDINGS: From December 2006 to May 2008, we completed enrollment of 1973 participants. Measured baseline characteristics did not differ significantly between the study arms. Enrollment was staggered by clinic pair and truncated at two matched sites. CONCLUSIONS: A large clinical trial of routing VL monitoring was successfully implemented in a dynamic and rapidly growing national ART program. Close collaboration with local health authorities and adequate reserve staff were critical to success. Randomized controlled trials such as this will likely prove valuable in determining long-term outcomes in resource-constrained settings. TRIAL REGISTRATION: Clinicaltrials.gov NCT00929604.

  1. Analysis of hepatitis C viral dynamics using Latin hypercube sampling

    Science.gov (United States)

    Pachpute, Gaurav; Chakrabarty, Siddhartha P.

    2012-12-01

    We consider a mathematical model comprising four coupled ordinary differential equations (ODEs) to study hepatitis C viral dynamics. The model includes the efficacies of a combination therapy of interferon and ribavirin. There are two main objectives of this paper. The first one is to approximate the percentage of cases in which there is a viral clearance in absence of treatment as well as percentage of response to treatment for various efficacy levels. The other is to better understand and identify the parameters that play a key role in the decline of viral load and can be estimated in a clinical setting. A condition for the stability of the uninfected and the infected steady states is presented. A large number of sample points for the model parameters (which are physiologically feasible) are generated using Latin hypercube sampling. An analysis of the simulated values identifies that, approximately 29.85% cases result in clearance of the virus during the early phase of the infection. Results from the χ2 and the Spearman's tests done on the samples, indicate a distinctly different distribution for certain parameters for the cases exhibiting viral clearance under the combination therapy.

  2. Association between HSV-2 and HIV-1 viral load in semen, cervico-vaginal secretions and genital ulcers of Thai men and women.

    Science.gov (United States)

    Chu, Kathryn; Jiamton, Sukhum; Pepin, Jacques; Cowan, Frances; Mahakkanukrauh, Bussakorn; Suttent, Ruengpung; Robinson, Noah J; Deslandes, Sylvie; Frost, Eric; Chaisilwattana, Pongsakdi; Suthipinittharm, Puan; Grosskurth, Heiner; Brown, David; Jaffar, Shabbar

    2006-10-01

    We studied the association between herpes simplex virus type-2 (HSV-2) and HIV-1 viralload in plasma, semen, cervico-vaginal secretions and genital ulcers. Forty-seven (68%) men and 57 (80%) women were HSV-2 antibody positive, of whom 12 (26%, 95% confidence interval [CI] 20, 32) and five (8%, 95% CI 4, 12), respectively, had HSV-2 genital shedding detected by polymerase chain reaction. The mean HIV-1 seminal and cervico-vaginal viral loads did not differ significantly according to the presence of HSV-2 shedding. Eleven men and 15 women presented with genital ulcers; all ulcers were due to HSV-2. Ten men and nine women were followed up over six days: the mean (95% CI) HIV-1 log viral load copies/mL in the genital ulcers at baseline and final visits were 2.5 (2.3, 2.7) and 3.1 (2.0, 4.2) for men and 3.0 (2.6, 3.4) and 2.7 (2.3, 3.1) for women. These findings do not support the hypothesis that HSV-2 increases the HIV-1 viral load in genital secretions.

  3. 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

  4. 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.

  5. Comparative evaluation of the performance of the Abbott RealTime HIV-1 assay for measurement of HIV-1 plasma viral load on genetically diverse samples from Greece

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    Paraskevis Dimitrios

    2011-01-01

    Full Text Available Abstract Background HIV-1 is characterized by increased genetic heterogeneity which tends to hinder the reliability of detection and accuracy of HIV-1 RNA quantitation assays. Methods In this study, the Abbott RealTime HIV-1 (Abbott RealTime assay was compared to the Roche Cobas TaqMan HIV-1 (Cobas TaqMan and the Siemens Versant HIV-1 RNA 3.0 (bDNA 3.0 assays, using clinical samples of various viral load levels and subtypes from Greece, where the recent epidemiology of HIV-1 infection has been characterized by increasing genetic diversity and a marked increase in subtype A genetic strains among newly diagnosed infections. Results A high correlation was observed between the quantitative results obtained by the Abbott RealTime and the Cobas TaqMan assays. Viral load values quantified by the Abbott RealTime were on average lower than those obtained by the Cobas TaqMan, with a mean (SD difference of -0.206 (0.298 log10 copies/ml. The mean differences according to HIV-1 subtypes between the two techniques for samples of subtype A, B, and non-A/non-B were 0.089, -0.262, and -0.298 log10 copies/ml, respectively. Overall, differences were less than 0.5 log10 for 85% of the samples, and >1 log10 in only one subtype B sample. Similarly, Abbott RealTime and bDNA 3.0 assays yielded a very good correlation of quantitative results, whereas viral load values assessed by the Abbott RealTime were on average higher (mean (SD difference: 0.160 (0.287 log10 copies/ml. The mean differences according to HIV-1 subtypes between the two techniques for subtype A, B and non-A/non-B samples were 0.438, 0.105 and 0.191 log10 copies/ml, respectively. Overall, the majority of samples (86% differed by less than 0.5 log10, while none of the samples showed a deviation of more than 1.0 log10. Conclusions In an area of changing HIV-1 subtype pattern, the Abbott RealTime assay showed a high correlation and good agreement of results when compared both to the Cobas TaqMan and bDNA 3

  6. Hepatitis C seroprevalence and correlation between viral load and viral genotype among primary care clients in Mexico Seroprevalencia de hepatitis C y correlación entre la carga viral y el genotipo viral en asistentes al nivel primario de atención enMéxico

    Directory of Open Access Journals (Sweden)

    Ana I Burguete-Garcia

    2011-01-01

    Full Text Available OBJECTIVE: To measure hepatitis C virus (HCV sero-prevalence, prevalence, hepatitis risk characteristics frequency, and genotype correlation with viral load among clients attending health care clinics. MATERIAL AND METHODS: Venous blood samples from l12 226 consecutive consenting adults were collected from January 2006 through December 2009. HCV antibodies were detected by immunoassay. HCV RNA was detected by qRT-PCR and viral genotype was performed by PCR and LIPA test. RESULTS: The HCV seroprevalence observed was l.5 % (C.I. 95% l.3-l.7, from seropositive individuals 60.9 % reported previous blood transfusion, 28.3% declared to have relatives with cirrhosis, 25.2% had tattoos or piercings, and 6.9% referred to have used drugs. Male gender and transfusion (pOBJETIVO: Medir la seroprevalencia y prevalencia del virus de hepatitis C (VHC, la frecuencia de caracteristicas de riesgo y la correlacion genotipica con la carga viral en sujetos asistentes a clinicas de medicina familiar. MATERIAL Y METODOS: muestras de sangre venosa se colectaron de l12 226 adultos, previo consentimiento informado, de enero 2006 hasta diciembre 2009, para la deteccion de anticuerpos contra VHC por ELISA. La deteccion de RNA-VHC y el genotipo viral se realizo mediante qRT-PCR. RESULTADOS: La seroprevalencia de VHC fue l.5 % (C.I. 95% l.3-l.7, 60.9% reportaron transfusion sanguinea previa, 28.3% dijo tener familiares cercanos con cirrosis, 25.2% tenian tatuajes o piercing y 6.9% refirio ser usuario de drogas intravenosas. El ser hombre, el antecedente de transfusiones y el uso de drogas (p<0.00l, fueron los factores con mayor frecuencia en el grupo VHC seropositivo. La prevalencia del RNA-VHC en seropositivos fue de 48.3%. El genotipo mas frecuente en todas las areas geograficas de Mexico fue el l (subtipo lA, 33%; subtipo lB, 21.4% seguido por el genotipo 2 (subtipo 2A, 8.50%. Se observó una correlación positiva de 51% con la carga viral más alta y el genotipo viral 1A

  7. Use of maraviroc in patients with undetectable viral load: efficacy, tolerance and predictors of viral response in MARAVIROC-cohort study

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    María Jesús Pérez Elías

    2014-11-01

    Full Text Available Introduction: No controlled clinical trials had studied the role of maraviroc (MRV in fully suppressed patients (1. Materials and Methods: MRV-cohort is an observational, retrospective, multicentric (27 sites large cohort study of patients starting MRV in clinical practice under different circumstances, with at least 48 weeks of follow-up. For the present analysis we selected all those patients starting with an HIV-RNA<50 copies/mL. Demographics, baseline CD4 cell count, past history of antiretroviral treatment (ART, tropism, reasons for MRV use, MRV based therapy and change/end of MRV use were assessed. Paired analysis of lipid, hepatic and kidney profile changes and univariate and multivariate analyses of HIV-RNA<50 copies/mL at 48 weeks were explored. Results: We included 247 out of 667 subjects from the entire cohort. At study entry, their median age was 47 years, 23% were women, 31% MSM, 49% had CDC category C, median CD4+ counts were 468 cells/mm3, 46% were HCV+ and 4.5% AgHBs+. Tropism information was available in 197 (94% R5. Median length of prior ARTV was 10.7 years, with exposure to a median of three drug families. Main reasons for prescribing MRV were: toxicity 38%, inmunodiscordance 23%, simplification 19% and admission in a clinical trial 10.4%. MRV based therapies used were MRV+2NRTIs 9%, MRV+PI 46%, MRV+PI+other 40% and MRV+other 5%. At 48 weeks, 23% of patients had changed or finished MRV therapy due to toxicity 2.4%, virological failure 2%, immunological failure 1.2%, simplification 3,2%, trial requirement 9.7%, medical decision 2.8%, treatment suspension 1.2% and unknown 0.4%. At 48 weeks, no significant changes were observed in lipid, hepatic or kidney profiles, and 85% of patients remained with HIV-RNA<50 copies/mL. Focusing on viral response univariate and multivariate models did not show any significant baseline variable explaining viral failure. Conclusions: In clinical practice MRV was used, mostly in R5 positive

  8. The contribution of Ebola viral load at admission and other patient characteristics to mortality in a Médecins Sans Frontières (MSF) Ebola Case Management Centre (CMC), Kailahun, Sierra Leone, June -October, 2014.

    LENUS (Irish Health Repository)

    Fitzpatrick, Gabriel

    2015-05-22

    This paper describes patient characteristics, including Ebola viral load, associated with mortality in an MSF Ebola case management centre. Out of 780 admissions between June and October 2014, 525 (67%) were positive for Ebola with a known outcome. The crude mortality rate was 51% (270\\/525). Ebola viral load (whole blood sample) data was available on 76% (397\\/525) of patients. Univariate analysis indicated viral load at admission, age, symptom duration prior to admission and distance travelled to the CMC were associated with mortality (p value<0.05). The multivariable model predicted mortality in those with a viral load at admission greater than 10 million copies per millilitre (p value<0.05, Odds Ratio>10), aged 50 years or more (p value=0.08, Odds Ratio=2) and symptom duration prior to admission less than 5 days (p value=0.14). The presence of confusion, diarrhoea and conjunctivitis were significantly higher (p value<0.05) in Ebola patients who died. These findings highlight the importance viral load at admission has on mortality outcomes and could be used to cohort cases with viral loads greater than 10 million copies into dedicated wards with more intensive medical support to further reduce mortality.

  9. Vacinação contra influenza em crianças infectadas pelo HIV: alterações imunológicas e na carga viral Influenza vaccination in HIV infected children: immunologic and viral load changes

    Directory of Open Access Journals (Sweden)

    Aroldo P. de Carvalho

    2003-02-01

    ças com condição clínica e imunológica não estável, principalmente se essas não estiverem sob terapêutica anti-retroviral eficaz.Objective: to identify whether influenza immunization in HIV infected children could increase HIV viral load and decrease CD4+ lymphocytes count as a consequence of the response induced by a T cell-dependent antigen. Methods: prospective, descriptive study, with 51 HIV infected children, vaccinated against influenza in 1999, in Florianópolis, Brazil. Blood samples were collected at three different moments: on the immunization day; between 14 and 20 days later; between 60 and 90 days later. Plasma levels of HIV viral load and CD4+ lymphocytes count were determined. Friedman ANOVA test, Student t-test for dependent samples, Bonferroni correction, and Wilcoxon matched test were performed for statistic analysis. Results: children's mean age was 6.08 years (1 to 12.9 years. The medians of CD4+ lymphocyte count on vaccination day and at the other two moments were 789, 645 and 768 cells/mm³, respectively. A significant reduction was observed in the CD4+ lymphocyte count between the first and the second analyses, but the same did not happen between the first and the third analyses. There was no significant difference of CD4+ lymphocyte percentage between the first and the second analyses. The median of HIV viral load values in log10 copies/ml was 4.38, 4.30 and 4.25, at the three moments respectively. Eight out of 44 patients (18.2% showed increase > 0.5 log10 copies/ml in HIV viral load between the first and the second analyses and among these, four returned to levels close to their base levels in the third analysis. Conclusion: there was no significant change in the CD4+ lymphocyte percentage, in spite of a transitory increase in HIV viral load after influenza vaccination. Caution should be used when administering vaccine against flu to children with no stable clinical and immunological conditions, mainly if they are not under effective anti

  10. Patients infected with CRF07_BC have significantly lower viral loads than patients with HIV-1 subtype B: mechanism and impact on disease progression.

    Directory of Open Access Journals (Sweden)

    Szu-Wei Huang

    Full Text Available The circulating recombinant form (CRF 07_BC is the most prevalent HIV-1 strain among injection drug users (IDUs in Taiwan. It contains a 7 amino-acid deletion in its p6gag. We conducted a cohort study to compare viral loads and CD4 cell count changes between patients infected with subtype B and CRF07_BC and to elucidate its mechanism. Twenty-one patients infected with CRF07_BC and 59 patients with subtype B were selected from a cohort of 667 HIV-1/AIDS patients whom have been followed up for 3 years. Generalized estimated equation was used to analyze their clinical data and the results showed that patients infected with CRF07_BC had significantly lower viral loads (about 58,000 copies per ml less than patients with subtype B infection (p = 0.002. The replicative capacity of nine CRF07_BC and four subtype B isolates were compared and the results showed that the former had significantly lower replicative capacity than the latter although all of them were CCR5- tropic and non-syncytium inducing viruses. An HIV-1-NL4-3 mutant virus which contains a 7 amino-acid deletion in p6gag (designated as 7d virus was generated and its live cycle was investigated. The results showed that 7d virus had significantly lower replication capacity, poorer protease-mediated processing and viral proteins production. Electron microscopic examination of cells infected with wild-type or 7d virus demonstrated that the 7d virus had poorer and slower viral maturation processes: more viruses attached to the cell membrane and higher proportion of immature virions outside the cells. The interaction between p6gag and Alix protein was less efficient in cells infected with 7d virus. In conclusion, patients infected with CRF07_BC had significantly lower viral loads than patients infected with subtype B and it may due to the deletion of 7 amino acids which overlaps with Alix protein-binding domain of the p6gag.

  11. Effect of mild-to-moderate smoking on viral load, cytokines, oxidative stress, and cytochrome P450 enzymes in HIV-infected individuals.

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    Anusha Ande

    Full Text Available Mild-to-moderate tobacco smoking is highly prevalent in HIV-infected individuals, and is known to exacerbate HIV pathogenesis. The objective of this study was to determine the specific effects of mild-to-moderate smoking on viral load, cytokine production, and oxidative stress and cytochrome P450 (CYP pathways in HIV-infected individuals who have not yet received antiretroviral therapy (ART. Thirty-two human subjects were recruited and assigned to four different cohorts as follows: a HIV negative non-smokers, b HIV positive non-smokers, c HIV negative mild-to-moderate smokers, and d HIV positive mild-to-moderate smokers. Patients were recruited in Cameroon, Africa using strict selection criteria to exclude patients not yet eligible for ART and not receiving conventional or traditional medications. Those with active tuberculosis, hepatitis B or with a history of substance abuse were also excluded. Our results showed an increase in the viral load in the plasma of HIV positive patients who were mild-to-moderate smokers compared to individuals who did not smoke. Furthermore, although we did not observe significant changes in the levels of most pro-inflammatory cytokines, the cytokine IL-8 and MCP-1 showed a significant decrease in the plasma of HIV-infected patients and smokers compared with HIV negative non-smokers. Importantly, HIV-infected individuals and smokers showed a significant increase in oxidative stress compared with HIV negative non-smoker subjects in both plasma and monocytes. To examine the possible pathways involved in increased oxidative stress and viral load, we determined the mRNA levels of several antioxidant and cytochrome P450 enzymes in monocytes. The results showed that the levels of most antioxidants are unaltered, suggesting their inability to counter oxidative stress. While CYP2A6 was induced in smokers, CYP3A4 was induced in HIV and HIV positive smokers compared with HIV negative non-smokers. Overall, the findings suggest

  12. Longitudinal comparison between plasma and seminal HIV-1 viral loads during antiretroviral treatment Comparação longitudinal entre cargas virais seminais e plasmáticas do HIV-1 durante terapia anti-retroviral

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    Lauro Ferreira da Silva Pinto Neto

    2003-12-01

    Full Text Available This study was designed to investigate the impact of anti-retroviral therapy on both plasma and seminal HIV-1 viral loads and the correlation between viral loads in these compartments after treatment. Viral load, CD4+ and CD8+ T-cell counts were evaluated in paired plasma and semen samples from 36 antiretroviral therapy-naïve patients at baseline and on days 45, 90, and 180 of treatment. Slopes for blood and seminal viral loads in all treated patients were similar (p = 0.21. Median HIV-1 RNA titers in plasma and semen at baseline were 4.95 log10 and 4.48 log10 copies/ml, respectively. After 180 days of therapy, the median viral load declined to 3.15 log10 copies/ml (plasma and 3.2 log10 copies/ml (semen. At this timepoint 22 patients presented HIV-1 viral load below 400 copies/ml in either plasma or semen, but only 9 had viral loads below 400 copies/ml in both compartments.Este estudo foi desenhado para investigar o impacto do tratamento com anti-retrovirais na evolução das cargas virais plasmáticas e seminais do HIV-1. A carga viral do HIV-1 e a contagem de linfócitos T CD4+ e CD8+ foi determinada em amostras pareadas de sangue e sêmen de 36 pacientes virgem de tratamento nos dias 0, 45, 90 e 180 após o início da terapia. As curvas de declínio das cargas virais plasmática e seminal foram semelhantes (p= 0.21. As medianas da carga viral plasmática e seminal no pré-tratamento (dia 0 foram 4.95 e 4.48 log10 cópias/ml, respectivamente. Seis meses após o início da terapia, a mediana da carga viral plasmática era 3.15 log10 cópias/ml e a seminal 3.2 log10 cópias/ml. Neste mesmo periodo, 22 pacientes apresentavam carga viral abaixo de 400 cópias/ml no plasma e/ou sêmen, enquanto apenas 9 pacientes apresentavam carga viral abaixo do limite de detecção nos dois compartimentos.

  13. MRKAd5 HIV-1 Gag/Pol/Nef vaccine-induced T-cell responses inadequately predict distance of breakthrough HIV-1 sequences to the vaccine or viral load.

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    Holly Janes

    Full Text Available BACKGROUND: The sieve analysis for the Step trial found evidence that breakthrough HIV-1 sequences for MRKAd5/HIV-1 Gag/Pol/Nef vaccine recipients were more divergent from the vaccine insert than placebo sequences in regions with predicted epitopes. We linked the viral sequence data with immune response and acute viral load data to explore mechanisms for and consequences of the observed sieve effect. METHODS: Ninety-one male participants (37 placebo and 54 vaccine recipients were included; viral sequences were obtained at the time of HIV-1 diagnosis. T-cell responses were measured 4 weeks post-second vaccination and at the first or second week post-diagnosis. Acute viral load was obtained at RNA-positive and antibody-negative visits. FINDINGS: Vaccine recipients had a greater magnitude of post-infection CD8+ T cell response than placebo recipients (median 1.68% vs 1.18%; p = 0·04 and greater breadth of post-infection response (median 4.5 vs 2; p = 0·06. Viral sequences for vaccine recipients were marginally more divergent from the insert than placebo sequences in regions of Nef targeted by pre-infection immune responses (p = 0·04; Pol p = 0·13; Gag p = 0·89. Magnitude and breadth of pre-infection responses did not correlate with distance of the viral sequence to the insert (p>0·50. Acute log viral load trended lower in vaccine versus placebo recipients (estimated mean 4·7 vs 5·1 but the difference was not significant (p = 0·27. Neither was acute viral load associated with distance of the viral sequence to the insert (p>0·30. INTERPRETATION: Despite evidence of anamnestic responses, the sieve effect was not well explained by available measures of T-cell immunogenicity. Sequence divergence from the vaccine was not significantly associated with acute viral load. While point estimates suggested weak vaccine suppression of viral load, the result was not significant and more viral load data would be needed to detect

  14. 前掠对高负荷风扇转子泄漏涡结构的影响%Numerically Investigating Effects of Highly-loaded and Forward-swept Fan Rotor on Tip Clearance Vortex

    Institute of Scientific and Technical Information of China (English)

    王雷; 刘波; 赵鹏程

    2012-01-01

    We numerically calculate the three-dimensional viscous flow field near the blade tip region at the near stall margin of a highly-loaded and forward-swept fan rotor. We compare the effects of the forward-swept fan rotor on the tip clearance vortex structure with those of a conventionally stacked radial rotor that has aerodynamically equal performance. The comparison results show that both the stall margin of the forward-swept fan rotor and the distribu- tion of its aerodynamic tip loading are improved. Our detailed analysis of its flow field reveals that the tip clearance vortex of the forward-swept fan rotor does not break under the near stall condition, thus providing a novel explanation why the tip clearance vortex structure of a forward-swept fan rotor is different from that of a conventional fan rotor.%以高负荷两级风扇第一级前掠转子为研究对象,通过数值模拟手段对近失速点叶尖流场进行了深入分析。为比较前掠对泄漏涡结构的影响,与同等气动性能下的常规转子进行了对比。结果表明前掠转子在近失速工况下泄漏涡涡心并未发生破碎,气动负荷展向分布更加均匀。对前掠转子不同于常规转子的叶尖泄漏涡结构产生机理提出了新的解释。

  15. HPV prophylactic vaccination in males improves the clearance of semen infection.

    Science.gov (United States)

    Foresta, Carlo; Garolla, Andrea; Parisi, Saverio; Ghezzi, Marco; Bertoldo, Alessandro; Di Nisio, Andrea; De Toni, Luca

    2015-10-01

    •We evaluated whether seroconversion in males influences HPV semen infection.•Naturally seroconverted patients showed reduced prevalence of HPV semen infection.•Naturally seroconverted patients also showed virtual absence of HPV multiple infection.•Prophylactic HPV vaccination induced clearance within 12 months from recruitment.•Seroconversion represents a key process involved in the clearance of the HPV.Available prophylactic vaccinations are considered of protective value for genital condyloma and precancerous lesions in female, but cost-effectiveness of the use of HPV vaccine in males is largely underinvestigated. HPV detection in semen is also an emerging problem in couples eligible for assisted reproduction techniques, since persistent infections are not compatible with repeated 6-months counselling-cycles to allow any spontaneous clearance of the virus in older infertile couples.In this study, we provide evidence that the development of seroconversion in human males affected by HPV infection in the genito-urinary tract, detected by HPV-DNA presence in the semen, has beneficial effects on the clearance of a viral load. Moreover, administration of prophylactic vaccination to HPV infected-seronegative patients induced seroconversion within 6 months from the first dosage administration, achieving 10 folds-higher antibody titre compared to natural seroconversion. If vaccine administration ameliorates the clearance of HPV semen infection, this could be a potential benefit to overcome fertility problems related to persistent HPV infections in males, after an obvious cost-effectiveness analysis.

  16. Generation of HIV-1 and Internal Control Transcripts as Standards for an In-House Quantitative Competitive RT-PCR Assay to Determine HIV-1 Viral Load

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    Anny Armas Cayarga

    2011-01-01

    Full Text Available Human immunodeficiency virus type-1 (HIV-1 viral load is useful for monitoring disease progression in HIV-infected individuals. We generated RNA standards of HIV-1 and internal control (IC by in vitro transcription and evaluated its performance in a quantitative reverse transcription polymerase chain reaction (qRT-PCR assay. HIV-1 and IC standards were obtained at high RNA concentrations, without DNA contamination. When these transcripts were included as standards in a qRT-PCR assay, it was obtained a good accuracy (±0.5 log10 unit of the expected results in the quantification of the HIV-1 RNA international standard and controls. The lower limit detection achieved using these standards was 511.0 IU/mL. A high correlation (=0.925 was obtained between the in-house qRT-PCR assay and the NucliSens easyQ HIV-1 test (bioMerieux for HIV-1 RNA quantitation with clinical samples (=14. HIV-1 and IC RNA transcripts, generated in this study, proved to be useful as standards in an in-house qRT-PCR assay for determination of HIV-1 viral load.

  17. Valine, a Branched-Chain Amino Acid, Reduced HCV Viral Load and Led to Eradication of HCV by Interferon Therapy in a Decompensated Cirrhotic Patient

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    Takumi Kawaguchi

    2012-10-01

    Full Text Available A decreased serum level of branched-chain amino acid (BCAA is a distinctive metabolic disorder in patients with liver cirrhosis. Recently, BCAA has been reported to exert various pharmacological activities, and valine, which is a BCAA, has been shown to affect lipid metabolism and the immune system in in vivo experiments. However, the clinical impact of valine supplementation on viral hepatitis C virus (HCV load has never been reported. Here, we first describe a case of HCV-related advanced liver cirrhosis that was treated by an oral valine agent. The administration of valine resulted in an improvement of fatigue and a reduction in hepatic fibrosis indexes as well as serum α-fetoprotein level. Furthermore, a marked reduction in HCV RNA levels was seen after valine treatment. The patient was then treated by interferon β, resulting in the successful eradication of chronic HCV infection. Thus, valine may be involved in the reduction of HCV viral load and could support a sustained virologic response to interferon therapy.

  18. Progress realized: trends in HIV-1 viral load and CD4 cell count in a tertiary-care center from 1999 through 2011.

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    Howard B Gale

    Full Text Available BACKGROUND: HIV-1 RNA and CD4 cell counts are important parameters for HIV care. The objective of this study was to assess the overall trends in HIV-1 viral load and CD4 cell counts within our clinic. METHODS: Patients with at least one of each test performed by the Infectious Diseases Laboratory from 1999 through 2011 were included in this analysis. By adapting a novel statistical model, log(10 HIV-1 RNA means were estimated by month, and log(10-transformed HIV-1 RNA means were estimated by calendar year. Geometric means were calculated for CD4 cell counts by month and calendar year. Log(10 HIV-1 RNA and CD4 cell count monthly means were also examined with polynomial regression. RESULTS: There were 1,814 individuals with approximately 25,000 paired tests over the 13-year observation period. Based on each patient's final value of the year, the percentage of patients with viral loads below the lower limit of quantitation rose from 29% in 1999 to 72% in 2011, while the percentage with CD4 counts <200 cells/µL fell from 31% to 11%. On average annually, the mean HIV-1 RNA decreased by 86 copies/mL and the mean CD4 counts increased by 16 cells/µL. For the monthly means, the correlations (R(2 from second-order polynomial regressions were 0.944 for log(10 HIV-1 RNA and 0.840 for CD4 cell counts. CONCLUSIONS: Marked improvements in HIV-1 RNA suppression and CD4 cell counts were achieved in a large inner-city population from 1999 through 2011. This success demonstrates that sustained viral control with improved immunologic status can be a realistic goal for most individuals in clinical care.

  19. The Contribution of Ebola Viral Load at Admission and Other Patient Characteristics to Mortality in a Médecins Sans Frontières Ebola Case Management Centre, Kailahun, Sierra Leone, June-October 2014.

    Science.gov (United States)

    Fitzpatrick, Gabriel; Vogt, Florian; Moi Gbabai, Osman B; Decroo, Tom; Keane, Marian; De Clerck, Hilde; Grolla, Allen; Brechard, Raphael; Stinson, Kathryn; Van Herp, Michel

    2015-12-01

    This paper describes patient characteristics, including Ebola viral load, associated with mortality in a Médecins Sans Frontières Ebola case management centre (CMC).Out of 780 admissions between June and October 2014, 525 (67%) were positive for Ebola with a known outcome. The crude mortality rate was 51% (270/525). Ebola viral load (whole-blood sample) data were available on 76% (397/525) of patients. Univariate analysis indicated viral load at admission, age, symptom duration prior to admission, and distance traveled to the CMC were associated with mortality (P 10), aged ≥ 50 years (P = .08, odds ratio = 2) and symptom duration prior to admission less than 5 days (P = .14). The presence of confusion, diarrhea, and conjunctivitis were significantly higher (P Ebola patients who died.These findings highlight the importance viral load at admission has on mortality outcomes and could be used to cohort cases with viral loads greater than 10 million copies into dedicated wards with more intensive medical support to further reduce mortality.

  20. 新型甲型H1N1流感患者体内病毒载量与胸部CT表现的关系%The relationship between chest CT findings and viral load in patients with novel influenza A( H1N1 )

    Institute of Scientific and Technical Information of China (English)

    陆普选; 叶如馨; 单万水; 周伯平; 邓莹莹; 杨桂林; 刘映霞; 干芸根; 李国保; 刘威龙; 刘艳; 张晶

    2010-01-01

    -pneumonia group (n = 20). The relationship between chest CT changes and viral load was observed and analyzed statistically using SPSS 10. 5 software. Results Patchy consolidations of lungs were the main findings in pneumonia group with influenza A( H1N1 )infection, and ground-glass opacities were the main CT findings at acute and convalescent phases.Lobular and segmental shadows of the lungs were diffusely distributed, mostly found in lower lungs,especially the left lung. In some cases, the lung diseases were accompanied with mediastinal lymphadenopathy. Co-existence of pulmonary parenchymal, interstitial and pleural diseases was observed.Peak viral load occurred at the early phase of illness, with the mean initial viral load being 7.7 copies/ml and 4. 2 copies/ml in the pneumonia and the non-pneumonia groups respectively. The viral nucleic acid became negative 4 days after antiviral treatment (course of 6 days). Dynamic observation of 3 patients with novel influenza A (H1N1 ) pneumonia showed that, the viral clearance period preceded the absorption of lung lesions in 2 cases, but viral clearance period of a young patient was significantly prolonged. ConclusionIn patients with the novel influenza A (H1N1) infection, the viral load in the pneumonia group was significantly higher than that in the group with normal chest imaging. Dynamic observation on chest imaging and viral load may be beneficial for clinicians to start prompt and effective treatment.

  1. Association of core promoter mutations of hepatitis B virus and viral load is different in HBeAg(+) and HBeAg(-) patients

    Institute of Scientific and Technical Information of China (English)

    Andi Utama; Benyamin Lukito; Tantoro Harmono; Nasrul Zubir; Julius; Soewignjo Soemohardjo; Laurentius Adrianus Lesmana; Ali Sulaiman; Susan Tai; Marlinang Diarta Siburian; Sigit Purwantomo; Mariana Destila Bayu Intan; Tri Shinta Kurniasih; Rino Alvani Gani; Wenny Astuti Achwan; Arnelis; Syafruddin AR Lelosutan

    2011-01-01

    AIM: To identify the prevalence of hepatitis B e antigen (HBeAg) and to assess the association of hepatitis B virus (HBV) core promoter mutations and viral load in Indonesian patients.METHODS: Sixty-four patients with chronic hepatitis,65 with liver cirrhosis and 50 with hepatocellular carcinoma were included in this study. HBeAg and hepatitis B e antibody (HBeAb) tests were performed using enzyme-linked immunosorbent assay and the mutations were analyzed by sequencing. Viral load was measured by real-time polymerase chain reaction.RESULTS: Of 179 patients, 108 (60.3%) were HBeAg(-) and 86 (79.6%) of these HBeAg(-) patients had been seroconverted. The A1896 mutation was not found in HBeAg(+) patients, however, this mutation was detected in 70.7% of HBeAg(-) patients. This mutation was frequently found when HBeAg was not expressed (87.7%), compared to that found in HBeAg seroconverted patients (65.1%). The A1899 mutation was also more prevalent in HBeAg(-) than in HBeAg(+) patients (P = 0.004). The T1762/A1764 mutation was frequently found in both HBeAg(+) and HBeAg(-) patients, however,the prevalence of this mutation did not significantly differ among the two groups (P = 0.054). In HBeAg(+)patients, the T1762/A1764 mutation was correlated with lower HBV DNA (P < 0.001). The A1899 mutation did not correlate with HBV DNA (P = 0.609). In HBeAg(-)patients, the T1762/A1764 mutation alone was not correlated with HBV DNA (P = 0.095), however, the presence of either the T1762/A1764 or A1896 mutations was associated with increased HBV DNA (P < 0.001).CONCLUSION: The percentage of HBeAg(-) patients is high in Indonesia, and most of the HBeAg(-) patients had been seroconverted. The A1896 mutation was most likely the major cause of HBeAg loss. The T1762/A1764 mutation alone was associated with lower viral loads in HBeAg(+) patients, but not in HBeAg(-) patients.

  2. Local immunosuppression induced by high viral load of human papillomavirus: characterization of cellular phenotypes producing interleukin-10 in cervical neoplastic lesions.

    Science.gov (United States)

    Prata, Thiago Theodoro Martins; Bonin, Camila Mareti; Ferreira, Alda Maria Teixeira; Padovani, Cacilda Tezelli Junqueira; Fernandes, Carlos Eurico dos Santos; Machado, Ana Paula; Tozetti, Inês Aparecida

    2015-09-01

    A specific immune response to human papillomavirus (HPV) in the cervical microenvironment plays a key role in eradicating infection and eliminating mutated cells. However, high-risk HPVs modulate immune cells to create an immunosuppressive microenvironment, and induce these immune cells to produce interleukin 10 (IL-10). This production of IL-10, in conjunction with HPV infection, contributes to the appearance of cervical neoplastic lesions. We sought to characterize the IL-10-producing cellular phenotype, and investigate the influence of host and HPV factors upon the induction of an immunosuppressive microenvironment. Immunohistochemical analysis demonstrated an increase in IL-10 production by keratinocytes, macrophages and Langerhans cells in high-grade cervical lesions and cervical cancer. This increase was more pronounced in patients older than 30 years, and was also correlated with high viral load, and infection with a single HPV type, particularly high-risk HPVs. Our results indicate the existence of a highly immunosuppressive microenvironment composed of different IL-10-producing cellular phenotypes in cervical cancer samples, and samples classified as high-grade cervical lesions (cervical intraepithelial neoplasia stages II and III). The immunosuppressive microenvironment that developed for these different cellular phenotypes favours viral persistence and neoplastic progression.

  3. Determination of HPV DNA viral load by hybrid capture assay and its association with cytological findings Determinação da carga viral de DNA de HPV pelo ensaio de captura híbrida e sua associação com achados citológicos

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    Inês Aparecida Tozetti

    2006-12-01

    Full Text Available OBJECTIVE: To compare the relation between HPV viral load by hybrid capture II test (HCII and cytological findings. METHODS: Three hundred sixty-two reagent samples to HPV DNA by HCII had their viral loads classified in four categories and correlated to cytological results. RESULTS: Twenty-two samples (6.1% were reagent only to low-risk oncogenic types (group A and 340 (93.9% were reagent to high-risk oncogenic types (group B. The correlation between viral load for the reagent samples to group A and cytological results showed low-grade squamous intraepithelial lesion (LSIL predominance (50%. Most of this group samples had viral load between 1 to OBJETIVO: Comparar a relação entre a carga viral do HPV por captura híbrida II (HCII e os achados citológicos. METODOS: Trezentas e sessenta e duas amostras reagentes para DNA de HPV por HCII tiveram suas cargas virais classificadas em quatro categorias e correlacionadas aos resultados citológicos. RESULTADOS: Vinte e duas amostras (6,1% foram reagentes somente para os tipos de baixo risco oncogênico (grupo A e 340 (93,9% foram reagentes para os tipos de alto risco oncogênico (grupo B. A correlação entre carga viral das amostras reagentes para o grupo A e resultados citológicos mostrou predominância (50% de lesão escamosa intraepitelial de baixo grau (LSIL. A maioria das amostras desse grupo teve carga viral entre 1 e < 10RLU/PCA. Nos pacientes reagentes para o grupo B observamos que 52,1% tiveram citologia LSIL e 38,2% tiveram citologia negativa para lesão intraepitelial e malignidade (NILM. Os pacientes com LSIL tiveram a carga viral bem distribuída, com ligeira predominância da categoria de 100 a < 1.000RLU/PCB. As amostras com carga viral entre 1 e < 10RLU/PCB mostraram predominância de citologia NILM (48.1%. Lesões escamosas de alto grau (3,4% foram presentes nas amostras com carga viral entre 100 e < 1.000RLU/PCB (p = 0,023. Houve correlação entre a mediana da carga viral para o

  4. Analysis of virological efficacy in trials of antiretroviral regimens: drawbacks of not including viral load measurements after premature discontinuation of therapy

    DEFF Research Database (Denmark)

    Kirk, Ole; Pedersen, Court; Law, Matthew;

    2002-01-01

    OBJECTIVES: To compare two analytic approaches to assess the virological effect of HAART according to the intention-to-treat (ITT) principle. MATERIAL: Data from 2318 patients enrolled in 10 randomised clinical trials (RCTs) and from 3091 patients followed in an observation cohort (Euro......SIDA) starting their first HAART regimen. METHODS: Two classifications of defining virological response 48 weeks after starting the therapy to be evaluated were compared: 1) only patients remaining on the therapy and having a plasma viral load (pVL) below a given cut-off level at week 48 were classified...... to ITT/s=f, 22-70% of the patients starting a HAART regimen in a RCT experienced a virological response at week 48. Only two RCTs had complete follow-up data (n=424): between 29 and 62% achieved a virological response at week 48 in the six treatment arms evaluated in the studies according to ITT...

  5. Creatinine clearance test

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/article/003611.htm Creatinine clearance test To use the sharing features on this page, please enable JavaScript. The creatinine clearance test helps provide information about how well the ...

  6. Prevalence and risk factors associated to chronic kidney disease in HIV-infected patients on HAART and undetectable viral load in Brazil.

    Directory of Open Access Journals (Sweden)

    Andréia M Menezes

    Full Text Available BACKGROUND: To determine the prevalence and associated factors with chronic kidney disease (CKD in a cohort of HIV-positive individuals with undetectable viral load on HAART. METHODS: From March, 2009 to September 2009, 213 individuals between 18-70 years, period on HAART ≥12 months, viral load < 50 copies/mm(3, and CD4 ≥ 200 cells/mm(3, were consecutively enrolled at the outpatient clinic of Hospital de Clínicas, Porto Alegre, Brazil. Exclusion criteria were obesity, malnourishment, amputee, paraplegic, previous history of renal disease, pregnancy and hepatic insufficiency. Renal function was determined by estimated glomerular filtration rate (eGFR assessed by the modification of diet in renal disease. CKD was defined as an eGFR less or equal than 60 ml/min/1.73 m(2, for a period of at least 3 months. Poisson regression was used to determine factors associated with CKD. RESULTS: CKD was diagnosed in 8.4% of the population, and after adjustment, the risk factors were hypertension (RR = 3.88, 95%CI, 1.84-8.16, time on HAART (RR = 1.15, 95%CI,1.03-1.27 and tenofovir exposure (RR = 2.25, 95%CI, 1.04-4.95. Higher weight (RR = 0.88 95%CI, 0.82-0.96 was associated to normal function. CONCLUSIONS: CKD was a common finding in this cohort of patients and was related to hypertension, time on HAART and tenofovir exposure. We suggest a more frequent monitoring of renal function, especially for those with risk factors to early identify renal impairment.

  7. T cell activation but not polyfunctionality after primary HIV infection predicts control of viral load and length of the time without therapy.

    Directory of Open Access Journals (Sweden)

    Andrea Cossarizza

    Full Text Available OBJECTIVE: Immune changes occurring after primary HIV infection (PHI have a pivotal relevance. Our objective was to characterize the polyfunctionality of immune response triggered by PHI, and to characterize immune activation and regulatory T cells, correlating such features to disease progression. PATIENTS AND METHODS: We followed 11 patients experiencing PHI for 4 years. By polychromatic flow cytometry, we studied every month, for the first 6 months, T lymphocyte polyfunctionality after cell stimulation with peptides derived from HIV-1 gag and nef. Tregs were identified by flow cytometry, and T cell activation studied by CD38 and HLA-DR expression. RESULTS: An increase of anti-gag and anti-nef CD8+ specific T cells was observed 3 months after PHI; however, truly polyfunctional T cells, also able to produce IL-2, were never found. No gross changes in Tregs were present. T lymphocyte activation was maximal 1 and 2 months after PHI, and significantly decreased in the following period. The level of activation two months after PHI was strictly correlated to the plasma viral load 1 year after infection, and significantly influenced the length of period without therapy. Indeed, 80% of patients with less than the median value of activated CD8+ (15.5% or CD4+ (0.9% T cells remained free of therapy for >46 months, while all patients over the median value had to start treatment within 26 months. CONCLUSIONS: T cell activation after PHI, more than T cell polyfunctionality or Tregs, is a predictive marker for the control of viral load and for the time required to start treatment.

  8. Pregnant women with HIV on ART in Europe: how many achieve the aim of undetectable viral load at term and are able to deliver vaginally?

    Directory of Open Access Journals (Sweden)

    Aebi-Popp K

    2012-11-01

    Full Text Available Purpose of the study Mother-to-child transmission rates in Europe are below 1% in HIV-infected women on successful combined antiretroviral therapy (cART irrespective of mode of delivery. Consequently, most national guidelines updated between 2001 and 2009 recommended vaginal deliveries for women with undetectable or very low viral load (VL. The aim of this study was to explore the impact of these new guidelines on the rates of vaginal deliveries following complete viral suppression on cART. Methods A pooled analysis of data on HIV-1-positive women enrolled in the Swiss Mother & Child HIV Cohort Study and the European Collaborative Study with a live birth between 2000 and 2010 was carried out. Deliveries were classified as occurring pre- or post-publication of national guidelines recommending vaginal delivery in women with low/ undetectable VL for each country. Summary of results Overall, 2527 mothers, 2848 deliveries and 2903 births were included from 10 countries. The women were mostly Caucasian (44% or black (47% and had a median age of 31 at the time of delivery. They were diagnosed with HIV a median of 3.3 years before pregnancy and 84% were CDC stage A with a median CD4 cell count of 450 cells/mm3. 17% reported a history of injecting-drug use (IDU and 3% current IDU. 29% of women conceived on cART, 63% started in pregnancy and 8% received no antenatal ART. The most common regimen used was PI based cART (50%. Of the deliveries, elective caesarean section (CS was carried out in 58%, emergency CS in 17% and vaginal delivery in 23%. Of 1869 women with a VL measure within the last trimester of pregnancy, only 65% had undetectable HIV-RNA. Overall, 21% of all deliveries occurring before the guideline change were vaginal, increasing to 48% subsequently. The proportion of women with undetectable VL having a CS decreased from 29% before to 13% after the guidelines update. Conclusions Nearly half of all deliveries subsequent to European guideline

  9. Turbomachinery Clearance Control

    Science.gov (United States)

    Chupp, Raymond E.; Hendricks, Robert C.; Lattime, Scott B.; Steinetz, Bruce M.; Aksit, Mahmut F.

    2007-01-01

    Controlling interface clearances is the most cost effective method of enhancing turbomachinery performance. Seals control turbomachinery leakages, coolant flows and contribute to overall system rotordynamic stability. In many instances, sealing interfaces and coatings are sacrificial, like lubricants, giving up their integrity for the benefit of the component. They are subjected to abrasion, erosion, oxidation, incursive rubs, foreign object damage (FOD) and deposits as well as extremes in thermal, mechanical, aerodynamic and impact loadings. Tribological pairing of materials control how well and how long these interfaces will be effective in controlling flow. A variety of seal types and materials are required to satisfy turbomachinery sealing demands. These seals must be properly designed to maintain the interface clearances. In some cases, this will mean machining adjacent surfaces, yet in many other applications, coatings are employed for optimum performance. Many seals are coating composites fabricated on superstructures or substrates that are coated with sacrificial materials which can be refurbished either in situ or by removal, stripping, recoating and replacing until substrate life is exceeded. For blade and knife tip sealing an important class of materials known as abradables permit blade or knife rubbing without significant damage or wear to the rotating element while maintaining an effective sealing interface. Most such tip interfaces are passive, yet some, as for the high-pressure turbine (HPT) case or shroud, are actively controlled. This work presents an overview of turbomachinery sealing. Areas covered include: characteristics of gas and steam turbine sealing applications and environments, benefits of sealing, types of standard static and dynamics seals, advanced seal designs, as well as life and limitations issues.

  10. Virological profile of pregnant HIV positive women with high levels of CD4 count in low income settings: Can viral load help as eligibility criteria for maternal triple ARV prophylaxis (WHO 2010 option B?

    Directory of Open Access Journals (Sweden)

    Anne Esther Njom Nlend

    2011-10-01

    Full Text Available INTRODUCTION: The objective of the study was to determine HIV-1 RNA load profile during pregnancy and assess the eligibility for the maternal triple antiretroviral prophylaxis. It was an observational cohort of pregnant HIV positive women ignorant of antiretroviral therapy with CD4 cell count of > 350/mm3. METHODS:Routine CD4 cell count assessment in HIV positive pregnant women completed by non exclusive measurement of the viral load by PCR /ARN in those with CD4 cell count > 350/mm3. Exclusion criteria: highly active antiretroviral therapy prior to pregnancy. RESULTS:Between January and December 2010, CD4 cell count was systematically performed in all pregnant women diagnosed as HIV-infected (n=266 in a referral center of 25 antenatal clinics. 63% (N=170 had CD4 cell count > 350/mm3, median: 528 (IQR: 421-625. 145 underwent measurement of viral load by PCR/RNA at a median gestational of 23 weeks of pregnancy (IQR: 19-28. Median viral load 4.4log10/ml, IQR (3.5-4.9.19/145(13% had an undetectable viral load of=1.8log10/ml. 89/145(61% had a viral load of = 4 log10/ml and were eligible for maternal triple ARV prophylaxis. CONCLUSION: More than 6 in 10 pregnant HIV positive women with CD4 cell count of > 350/mm3 may require triple antiretroviral for prophylaxis of MTCT. Regardless of cost, such results are conclusive and may be considered in HIV high burden countries for universal access to triple antiretroviral prophylaxis in order to move towards virtual elimination of HIV MTCT.

  11. [Parameters of the CD4-Cell count and viral load in human immunodeficiency virus type 1 (HIV-1) infected patients].

    Science.gov (United States)

    Selimova, L M; Serebrovskaya, L V; Ivanova, L A; Kravchenko, A V; Buravtsova, E V

    2015-01-01

    In this work the specific features of parameters of plasma CD4 T-lymphocytes count and level virus RNA in the HIV-infected patients were studied. 22% correlation between reduction of CD4 cell count and an increase in virus RNA level was observed in persons that did not receive antiretroviral treatment during the third HIV-infection phase. During this phase of infection patients exhibited a growth of the median value of virus load in cases of both rise as decline in CD4 cell count during long observation period. In addition, towards the end of the observation period, the percentage of patients with virus load > 3.3 Ig copies/ml considerably expanded. 43% correlation between CD4 cell count and duration of the HIV-infection was detected during the fourth infection phase in persons that did not receive antiretroviral treatment. Most of the patients in the third and the fourth infection phases had essential CD4 cell count growth during antiretroviral treatment. Best values were observed in patients with the initial value of CD4 > 400 cells/μl belonging to the third HIV-infection phase.

  12. Interferon Alpha Induces Sustained Changes in NK Cell Responsiveness to Hepatitis B Viral Load Suppression In Vivo

    Science.gov (United States)

    Gill, Upkar S.; Peppa, Dimitra; Micco, Lorenzo; Singh, Harsimran D.; Carey, Ivana; Foster, Graham R.; Maini, Mala K.; Kennedy, Patrick T. F.

    2016-01-01

    NK cells are important antiviral effectors, highly enriched in the liver, with the potential to regulate immunopathogenesis in persistent viral infections. Here we examined whether changes in the NK pool are induced when patients with eAg-positive CHB are ‘primed’ with PegIFNα and importantly, whether these changes are sustained or further modulated long-term after switching to nucleos(t)ides (sequential NUC therapy), an approach currently tested in the clinic. Longitudinal sampling of a prospectively recruited cohort of patients with eAg+CHB showed that the cumulative expansion of CD56bright NK cells driven by 48-weeks of PegIFNα was maintained at higher than baseline levels throughout the subsequent 9 months of sequential NUCs. Unexpectedly, PegIFNα-expanded NK cells showed further augmentation in their expression of the activating NK cell receptors NKp30 and NKp46 during sequential NUCs. The expansion in proliferating, functional NK cells was more pronounced following sequential NUCs than in comparison cohorts of patients treated with de novo NUCs or PegIFNα only. Reduction in circulating HBsAg concentrations, a key goal in the path towards functional cure of CHB, was only achieved in those patients with enhancement of NK cell IFNγ and cytotoxicity but decrease in their expression of the death ligand TRAIL. In summary, we conclude that PegIFNα priming can expand a population of functional NK cells with an altered responsiveness to subsequent antiviral suppression by NUCs. Patients on sequential NUCs with a distinct NK cell profile show a decline in HBsAg, providing mechanistic insights for the further optimisation of treatment strategies to achieve sustained responses in CHB. PMID:27487232

  13. Dynamic analysis of double-row self-aligning ball bearings due to applied loads, internal clearance, surface waviness and number of balls

    Science.gov (United States)

    Zhuo, Yaobin; Zhou, Xiaojun; Yang, Chenlong

    2014-11-01

    In this paper, a three degrees of freedom (dof) model was established for a double-row self-aligning ball bearing (SABB) system, and was applied to study the dynamic behavior of the system during starting process and constant speed rotating process. A mathematical model was developed concerning stiffness and damping characteristics of the bearing, as well as three-dimensional applied load, rotor centrifugal force, etc. Balls and races were all considered as nonlinear springs, and the contact force between ball and race was calculated based on classic Hertzian elastic contact deformation theory and deformation compatibility theory. The changes of each ball's contact force and loaded angle of each row were taken into account. In order to solve the nonlinear dynamical equilibrium equations of the system, these equations were rewritten as differential equations and the fourth order Runge-Kutta method was used to solve the equations iteratively. In order to verify accuracy of the dynamical model and correctness of the numerical solution method, a kind of SABB-BRF30 was chosen for case studies. The effects of several important governing parameters, such as radial and axial applied loads, normal internal, inner and outer races waviness, and number of balls were investigated. These parametric studies led to a complete characterization of the shaft-bearing system vibration transmission. The research provided a theoretical reference for new type bearing design, shaft-bearing system kinetic analysis, optimal design, etc.

  14. Viral Hepatitis

    Science.gov (United States)

    ... Public Home » For Veterans and the Public Viral Hepatitis Menu Menu Viral Hepatitis Viral Hepatitis Home For ... the Public Veterans and Public Home How is Hepatitis C Treated? Find the facts about the newest ...

  15. Evaluation of the Whole-Blood Alere Q NAT Point-of-Care RNA Assay for HIV-1 Viral Load Monitoring in a Primary Health Care Setting in Mozambique.

    Science.gov (United States)

    Jani, Ilesh V; Meggi, Bindiya; Vubil, Adolfo; Sitoe, Nádia E; Bhatt, Nilesh; Tobaiwa, Ocean; Quevedo, Jorge I; Loquiha, Osvaldo; Lehe, Jonathan D; Vojnov, Lara; Peter, Trevor F

    2016-08-01

    Viral load testing is the WHO-recommended monitoring assay for patients on HIV antiretroviral therapy (ART). Point-of-care (POC) assays may help improve access to viral load testing in resource-limited settings. We compared the performance of the Alere Q NAT POC viral load technology (Alere Technologies, Jena, Germany), measuring total HIV RNA using finger prick capillary whole-blood samples collected in a periurban health center, with that of a laboratory-based plasma RNA test (Roche Cobas Ampliprep/Cobas TaqMan v2) conducted on matched venous blood samples. The whole-blood Alere Q NAT POC assay produced results with a bias of 0.8593 log copy/ml compared to the laboratory-based plasma assay. However, at above 10,000 copies/ml, the bias was 0.07 log copy/ml. Using the WHO-recommended threshold to determine ART failure of 1,000 copies/ml, the sensitivity and specificity of the whole-blood Alere Q NAT POC assay were 96.83% and 47.80%, respectively. A cutoff of 10,000 copies/ml of whole blood with the Alere Q NAT POC assay appears to be a better predictor of ART failure threshold (1,000 copies/ml of plasma), with a sensitivity of 84.0% and specificity of 90.3%. The precision of the whole-blood Alere Q NAT POC assay was comparable to that observed with the laboratory technology (5.4% versus 7.5%) between detectable paired samples. HIV POC viral load testing is feasible at the primary health care level. Further research on the value of whole-blood viral load to monitor antiretroviral therapy is warranted.

  16. Relationship of peripheral blood T cell subset levels and PD-1/PD-L1 expression levels with viral load in patients with asymptomatic HIV infection

    Institute of Scientific and Technical Information of China (English)

    Xi-Li Miao; Si-Qing Mei; Gui-Min Gao

    2016-01-01

    Objective:To study the relationship of different T cell subset levels and PD-1/PD-L1 expression levels in peripheral blood with viral load in patients with asymptomatic HIV infection.Methods:Patients with asymptomatic HIV infection treated in our hospital from April 2012 to October 2015 were selected as the HIV group of the study, healthy subjects during the same period were selected as the control group, and peripheral blood was collected to detect CD3+CD4+CD8-, CD3+CD4-CD8+, CD4+CD25+Foxp3+ and CD4+CD25+CD127low/-cell levels as well as PD-1/PD-L1 expression levels.Results:The number and percentage of CD3+CD4+CD8- cells as well as the number of CD4+CD25+Foxp3+ and CD4+CD25+CD127low/-cells in peripheral blood of HIV group were significantly lower than those of control group, the number and percentage of CD3+CD4-CD8+ cells, the percentage of CD4+CD25+Foxp3+and CD4+CD25+CD127low/- cells as well as the expression levels of PD-L1 and PD-1 on CD4+T cell surface were significantly higher than those of control group, and the expression levels of PD-L1 and PD-1 on CD8+T cell surface were not significantly different from those of control group; the greater the viral load in HIV group, the lower the percentage of CD3+CD4+CD8-, and the higher the percentage of CD3+CD4-CD8+, CD4+CD25+Foxp3+ and CD4+CD25+CD127low/-cells as well the PD-1/PD-L1 positive percentage on CD4+T cell surface in peripheral blood. Conclusions:The immune characteristics of patients with asymptomatic HIV infection are the decreased number of CD4+T cells and the increased number of CD8+T cells as well as the decreased absolute content and increased relative content of CD4+CD25+Treg cells, and PD-1/PD-L1 pathway is the molecular mechanism of HIV to act on CD4+T cells.

  17. Switching HIV treatment in adults based on CD4 count versus viral load monitoring: a randomized, non-inferiority trial in Thailand.

    Directory of Open Access Journals (Sweden)

    Gonzague Jourdain

    2013-08-01

    Full Text Available BACKGROUND: Viral load (VL is recommended for monitoring the response to highly active antiretroviral therapy (HAART but is not routinely available in most low- and middle-income countries. The purpose of the study was to determine whether a CD4-based monitoring and switching strategy would provide a similar clinical outcome compared to the standard VL-based strategy in Thailand. METHODS AND FINDINGS: The Programs for HIV Prevention and Treatment (PHPT-3 non-inferiority randomized clinical trial compared a treatment switching strategy based on CD4-only (CD4 monitoring versus viral-load (VL. Consenting participants were antiretroviral-naïve HIV-infected adults (CD4 count 50-250/mm(3 initiating non-nucleotide reverse transcriptase inhibitor (NNRTI-based therapy. Randomization, stratified by site (21 public hospitals, was performed centrally after enrollment. Clinicians were unaware of the VL values of patients randomized to the CD4 arm. Participants switched to second-line combination with confirmed CD4 decline >30% from peak (within 200 cells from baseline in the CD4 arm, or confirmed VL >400 copies/ml in the VL arm. Primary endpoint was clinical failure at 3 years, defined as death, new AIDS-defining event, or CD4 400 copies/ml at switch was 7.2 months (5.8-8.0 in VL versus 15.8 months (8.5-20.4 in CD4 (p=0.002. FDO scores were not significantly different at time of switch. No adverse events related to the monitoring strategy were reported. CONCLUSIONS: The 3-year rates of clinical failure and loss of treatment options did not differ between strategies although the longer-term consequences of CD4 monitoring would need to be investigated. These results provide reassurance to treatment programs currently based on CD4 monitoring as VL measurement becomes more affordable and feasible in resource-limited settings. TRIAL REGISTRATION: ClinicalTrials.govNCT00162682 Please see later in the article for the Editors' Summary.

  18. Complement lysis activity in autologous plasma is associated with lower viral loads during the acute phase of HIV-1 infection.

    Directory of Open Access Journals (Sweden)

    Michael Huber

    2006-11-01

    Full Text Available BACKGROUND: To explore the possibility that antibody-mediated complement lysis contributes to viremia control in HIV-1 infection, we measured the activity of patient plasma in mediating complement lysis of autologous primary virus. METHODS AND FINDINGS: Sera from two groups of patients-25 with acute HIV-1 infection and 31 with chronic infection-were used in this study. We developed a novel real-time PCR-based assay strategy that allows reliable and sensitive quantification of virus lysis by complement. Plasma derived at the time of virus isolation induced complement lysis of the autologous virus isolate in the majority of patients. Overall lysis activity against the autologous virus and the heterologous primary virus strain JR-FL was higher at chronic disease stages than during the acute phase. Most strikingly, we found that plasma virus load levels during the acute but not the chronic infection phase correlated inversely with the autologous complement lysis activity. Antibody reactivity to the envelope (Env proteins gp120 and gp41 were positively correlated with the lysis activity against JR-FL, indicating that anti-Env responses mediated complement lysis. Neutralization and complement lysis activity against autologous viruses were not associated, suggesting that complement lysis is predominantly caused by non-neutralizing antibodies. CONCLUSIONS: Collectively our data provide evidence that antibody-mediated complement virion lysis develops rapidly and is effective early in the course of infection; thus it should be considered a parameter that, in concert with other immune functions, steers viremia control in vivo.

  19. Multicenter Evaluation of Whole-Blood Epstein-Barr Viral Load Standardization Using the WHO International Standard

    Science.gov (United States)

    Semenova, Touyana; Lupo, Julien; Alain, Sophie; Perrin-Confort, Gwladys; Grossi, Laurence; Dimier, Julie; Epaulard, Olivier; Morand, Patrice

    2016-01-01

    The first WHO international standard for Epstein-Barr virus (EBV) (WHO EBV standard) for nucleic acid amplification technology (NAT)-based assays was commercialized in January 2012 by the National Institute for Biological Standards and Control. In the study reported here, we compared whole-blood EBV DNA load (EDL) results from 12 French laboratories for seven samples (Quality Controls for Molecular Diagnostics 2013 proficiency panel) in order to determine whether expression in international units reduces interlaboratory variability in whole-blood EDLs. Each testing laboratory used a conversion factor to convert EDL results from copies per milliliter to international units per milliliter. This conversion factor was calculated from the WHO EBV standard according to the protocol described in this study (nine laboratories) or the recommendations of the PCR kit suppliers (three laboratories). The interlaboratory variability in whole-blood EDL results was reduced after standardization of the results using the WHO EBV standard. For the seven samples tested, standard deviations (SD) ranged from 0.41 to 0.55 when the results were expressed in log copies per milliliter, whereas the SD ranged from 0.17 to 0.32 when results were given in log international units per milliliter. Comparing the variance data (F test), we showed that the dispersion of whole-blood EDL results was significantly lower when they were expressed in log international units per milliliter (P < 0.001 for six of seven samples and P < 0.05 for one sample with a low mean EDL of 2.62 log IU/ml). This study showed that the use of the WHO EBV standard could improve the homogeneity of whole-blood EDL results between laboratories as well as the monitoring of patients at high risk of posttransplant lymphoproliferative disorders or other EBV-associated diseases. PMID:27076661

  20. Multicenter Evaluation of Whole-Blood Epstein-Barr Viral Load Standardization Using the WHO International Standard.

    Science.gov (United States)

    Semenova, Touyana; Lupo, Julien; Alain, Sophie; Perrin-Confort, Gwladys; Grossi, Laurence; Dimier, Julie; Epaulard, Olivier; Morand, Patrice; Germi, Raphaële

    2016-07-01

    The first WHO international standard for Epstein-Barr virus (EBV) (WHO EBV standard) for nucleic acid amplification technology (NAT)-based assays was commercialized in January 2012 by the National Institute for Biological Standards and Control. In the study reported here, we compared whole-blood EBV DNA load (EDL) results from 12 French laboratories for seven samples (Quality Controls for Molecular Diagnostics 2013 proficiency panel) in order to determine whether expression in international units reduces interlaboratory variability in whole-blood EDLs. Each testing laboratory used a conversion factor to convert EDL results from copies per milliliter to international units per milliliter. This conversion factor was calculated from the WHO EBV standard according to the protocol described in this study (nine laboratories) or the recommendations of the PCR kit suppliers (three laboratories). The interlaboratory variability in whole-blood EDL results was reduced after standardization of the results using the WHO EBV standard. For the seven samples tested, standard deviations (SD) ranged from 0.41 to 0.55 when the results were expressed in log copies per milliliter, whereas the SD ranged from 0.17 to 0.32 when results were given in log international units per milliliter. Comparing the variance data (F test), we showed that the dispersion of whole-blood EDL results was significantly lower when they were expressed in log international units per milliliter (P < 0.001 for six of seven samples and P < 0.05 for one sample with a low mean EDL of 2.62 log IU/ml). This study showed that the use of the WHO EBV standard could improve the homogeneity of whole-blood EDL results between laboratories as well as the monitoring of patients at high risk of posttransplant lymphoproliferative disorders or other EBV-associated diseases.

  1. Security Clearance Tracking System

    Data.gov (United States)

    National Archives and Records Administration — SCTS supports the adjudication process of private background investigations and clearances for potential employees, contractors, interns and student workers.

  2. Restoration of Innate and Adaptive Immune Responses by HCV Viral Inhibition with an Induction Approach Using Natural Interferon-Beta in Chronic Hepatitis C

    Directory of Open Access Journals (Sweden)

    Y. Kishida

    2012-01-01

    Full Text Available Chronic hepatitis C (CHC is a serious medical problem necessitating more effective treatment. This study investigated the hypothesis that an induction approach with nIFN-beta for 24 weeks followed by PEG-IFN-alpha+ribavirin (standard of care: SOC for 48 weeks (novel combination treatment: NCT would increase the initial virologic response rate and restore innate and adaptive immune responses in CHC. Seven CHC patients with a high viral load and genotype 1b were treated with NCT. Serum cytokine and chemokine levels were evaluated during NCT. NCT prevented viral escape and breakthrough resulting in persistent viral clearance of HCVRNA. IL-15 was increased at the end of induction therapy in both early virologic responders (EAVRs and late virologic responders (LAVRs; CXCL-8, CXCL-10, and CCL-4 levels were significantly decreased (<0.05 in EAVR but not in LAVR during NCT, and IL-12 increased significantly (<0.05 and CXCL-8 decreased significantly (<0.05 after the end of NCT in EAVR but not in LAVR. NCT prevented viral breakthrough with viral clearance leading to improvement of innate and adaptive immunity resulting in a sustained virologic response (SVR. NCT (=8 achieved a higher SVR rate than SOC (=8 in difficult-to-treat CHC patients with genotype 1 and high viral loads.

  3. Analysis of virological efficacy in trials of antiretroviral regimens: drawbacks of not including viral load measurements after premature discontinuation of therapy

    DEFF Research Database (Denmark)

    Kirk, Ole; Pedersen, Court; Law, Matthew;

    2002-01-01

    OBJECTIVES: To compare two analytic approaches to assess the virological effect of HAART according to the intention-to-treat (ITT) principle. MATERIAL: Data from 2318 patients enrolled in 10 randomised clinical trials (RCTs) and from 3091 patients followed in an observation cohort (EuroSIDA) star......OBJECTIVES: To compare two analytic approaches to assess the virological effect of HAART according to the intention-to-treat (ITT) principle. MATERIAL: Data from 2318 patients enrolled in 10 randomised clinical trials (RCTs) and from 3091 patients followed in an observation cohort (Euro......SIDA) starting their first HAART regimen. METHODS: Two classifications of defining virological response 48 weeks after starting the therapy to be evaluated were compared: 1) only patients remaining on the therapy and having a plasma viral load (pVL) below a given cut-off level at week 48 were classified...... to ITT/s=f, 22-70% of the patients starting a HAART regimen in a RCT experienced a virological response at week 48. Only two RCTs had complete follow-up data (n=424): between 29 and 62% achieved a virological response at week 48 in the six treatment arms evaluated in the studies according to ITT...

  4. A Self-Reported Adherence Measure to Screen for Elevated HIV Viral Load in Pregnant and Postpartum Women on Antiretroviral Therapy

    Science.gov (United States)

    Brittain, Kirsty; Mellins, Claude A.; Zerbe, Allison; Remien, Robert H.; Abrams, Elaine J.; Myer, Landon; Wilson, Ira B.

    2016-01-01

    Maternal adherence to antiretroviral therapy (ART) is a concern and monitoring adherence presents a significant challenge in low-resource settings. We investigated the association between self-reported adherence, measured using a simple three-item scale, and elevated viral load (VL) among HIV-infected pregnant and postpartum women on ART in Cape Town, South Africa. This is the first reported use of this scale in a non-English speaking setting and it achieved good psychometric characteristics (Cronbach α = 0.79). Among 452 women included in the analysis, only 12 % reported perfect adherence on the self-report scale, while 92 % had a VL <1000 copies/mL. Having a raised VL was consistently associated with lower median adherence scores and the area under the curve for the scale was 0.599, 0.656 and 0.642 using a VL cut-off of ≥50, ≥1000 and ≥10000 copies/mL, respectively. This simple self-report adherence scale shows potential as a first-stage adherence screener in this setting. Maternal adherence monitoring in low resource settings requires attention in the era of universal ART, and the value of this simple adherence scale in routine ART care settings warrants further investigation. PMID:27278548

  5. Effect of a CCR5 inhibitor on viral loads in macaques dual-infected with R5 and X4 primate immunodeficiency viruses.

    Science.gov (United States)

    Wolinsky, Steven M; Veazey, Ronald S; Kunstman, Kevin J; Klasse, Per Johan; Dufour, Jason; Marozsan, Andre J; Springer, Martin S; Moore, John P

    2004-10-10

    Human immunodeficiency virus type 1 (HIV-1) fusion with its target cells is initiated by sequential interactions between its envelope glycoprotein, CD4, and a co-receptor, usually CCR5 or CXCR4. Small molecules that bind to CCR5 and prevent its use by R5 HIV-1 strains are now being developed clinically as antiviral drugs. To test whether a block to CCR5 promotes the replication of viruses that enter cells via CXCR4 and are associated with accelerated disease progression, we administered a small molecule CCR5 inhibitor, CMPD 167, to three macaques dual-infected with both R5 (SIVmac251) and X4 (SHIV-89.6P) viruses. CMPD 167 caused a rapid and substantial (on average, 50-fold) suppression of R5 virus replication in each animal. In two of the animals, but not in the third, a rapid, transient, 8- to 15-fold increase in the amount of plasma X4 virus occurred. In neither animal was the increase in X4 viral load sustained throughout therapy, however. These observations may have relevance for the development of CCR5 inhibitors for treatment of HIV-1 infection of humans.

  6. Joint longitudinal hurdle and time-to-event models: an application related to viral load and duration of the first treatment regimen in patients with HIV initiating therapy.

    Science.gov (United States)

    Brilleman, Samuel L; Crowther, Michael J; May, Margaret T; Gompels, Mark; Abrams, Keith R

    2016-09-10

    Shared parameter joint models provide a framework under which a longitudinal response and a time to event can be modelled simultaneously. A common assumption in shared parameter joint models has been to assume that the longitudinal response is normally distributed. In this paper, we instead propose a joint model that incorporates a two-part 'hurdle' model for the longitudinal response, motivated in part by longitudinal response data that is subject to a detection limit. The first part of the hurdle model estimates the probability that the longitudinal response is observed above the detection limit, whilst the second part of the hurdle model estimates the mean of the response conditional on having exceeded the detection limit. The time-to-event outcome is modelled using a parametric proportional hazards model, assuming a Weibull baseline hazard. We propose a novel association structure whereby the current hazard of the event is assumed to be associated with the current combined (expected) outcome from the two parts of the hurdle model. We estimate our joint model under a Bayesian framework and provide code for fitting the model using the Bayesian software Stan. We use our model to estimate the association between HIV RNA viral load, which is subject to a lower detection limit, and the hazard of stopping or modifying treatment in patients with HIV initiating antiretroviral therapy. Copyright © 2016 John Wiley & Sons, Ltd.

  7. 母乳喂养对婴儿唾液巨细胞病毒载量的影响%Effect of breastfeeding on infant cytomegalovirus viral load

    Institute of Scientific and Technical Information of China (English)

    张琳; 王淮燕; 梅涛; 杨利民; 史烨; 虞斌

    2014-01-01

    目的 对先天性巨细胞病毒(CMV)感染的新生儿进行随访监测,探讨母乳喂养对CMV载量变化的影响.方法 采集2010年11月至2012年2月在常州市妇幼保健院山生的新生儿唾液进行CMV感染筛查,排除早产、严重感染性疾病或畸形等,对阳性感染且.无症状的足月新生儿根据母亲自主选择分成人工喂养组及母乳喂养组,随访至6个月,分别在出生1个月内、3个月、6个月采集唾液及母乳,采取实时荧光定量PCR法检测CMV-DNA的载量变化,同时行体格检查、头颅B超检查、耳声发射听力筛查、肝功能、血常规分析等检查.结果 30例婴儿在随访的6个月中均末发现有CMV感染性疾病的表现.人工喂养组与母乳喂养组婴儿在出生1个月内、3个月、6个月唾液巨细胞DNA载量末见明显变化(t=2.832、3.161、3.475,P均>0.05).母乳喂养组乳汁在山生1个月内、3个月、6个月CMV-DNA载量分别为3.125×103±2.017×102、2.688×103±2.251×102、3.016×103 ±2.613×102,三者比较差异无统计学意义(F=1.725,P=0.667).头颅B超检查、耳声发射听力筛查、肝功能、血常规分析等检查末见明显异常.结论 CMV感染的足月无症状新生儿,即便母乳中CMV 阳性,继续母乳喂养后婴儿体内的病毒载量也不会增加,也末发现继发性的症状感染.%Objective Follow-up monitoring was carried out in infants infected with cytomegalovirus (CMV) so as to find out whether breastfeeding could bring about changes of CMV viral load.Methods Saliva of the neonates born in Changzhou Maternal and Child Health Hospital from Nov.2010 to Feb.2012,was collected for CMV screening.Premature infants,or the infants with seriously infectious diseases and deformities were excluded,such as severe intrauterine infection,congenital immune deficiency disease and so on.The full-term infants with aymptomatic infection were divided into the artificial feeding group and the breastfeeding group

  8. Avaliação de ensaio molecular para determinação de carga viral em indivíduos sorologicamente negativos para o HIV-1 Evaluation of a molecular assay for determining viral load on HIV-1 antibody negative patients

    Directory of Open Access Journals (Sweden)

    José Moreira Pereira

    2002-01-01

    Full Text Available O teste de carga viral foi concebido para acompanhar a evolução e o tratamento do paciente com diagnóstico confirmado de HIV-1. Contudo, sua especificidade diagnóstica não foi ainda avaliada em pessoas que apresentam um teste sorológico negativo. Mesmo assim, ele tem sido erroneamente utilizado para o diagnóstico da infecção primária pelo HIV-1. Este trabalho relata quatro pacientes em que a carga viral plasmática NucliSens (Organon Teknika foi repetidamente positiva na ausência de anticorpos para HIV e chama atenção para o fato de que a carga viral abaixo de 10 mil cópias/ml é de difícil interpretação, como tem sido assinalado em numerosos artigos, em que foram utilizadas outras metodologias.The plasma viral load test for HIV-1,a exquisitely high sensitive assay, were neither developed nor evaluated for the diagnosis of primary HIV infection; therefore, their diagnostic specificity is not well delineated when applied to persons who are negative for HIV antibody. This article reported four cases of false positive results obtained by using NucliSens viral load assay (Organon Teknika and emphasize the importance that low positive plasma viral load (< 10 000 copies/ml may be difficult to interpret how has been assinalated in numerous articles in the medical literature, using other methodologies.

  9. Post-renal-transplant hypertension. Urine volume, free water clearance and plasma concentrations of arginine vasopressin, angiotensin II and aldosterone before and after oral water loading in hypertensive and normotensive renal transplant recipients.

    Science.gov (United States)

    Pedersen, E B; Danielsen, H; Knudsen, F; Nielsen, A H; Jensen, T; Kornerup, H J; Madsen, M

    1986-09-01

    Urine volume (V), free water clearance (CH2O) and plasma concentrations of arginine vasopressin (AVP), angiotensin II (A II) and aldosterone (Aldo) were determined before and three times during the first 5 h after an oral water load of 20 ml/kg body wt in 19 patients with post-renal-transplant hypertension (group I), in 13 normotensive renal transplant recipients (group II) and in 20 control subjects (group III). Both V and CH2O increased significantly in all groups, but considerably less in groups I and II than in group III. When CH2O was related to glomerular filtration rate no differences existed between patients and control subjects. Basal AVP was the same in groups I (3.3 pmol/l, median) and II (3.0 pmol/l), but significantly (p less than 0.01) higher than in group III (1.9 pmol/l). Basal A II was significantly (p less than 0.01) elevated in group I (18 pmol/l) when compared to both groups II (10 pmol/l) and III (11 pmol/l), and the level was independent of the presence of native kidneys. Basal Aldo was the same in all groups. During loading, AVP was reduced in all groups, A II was almost unchanged, and Aldo was increased in groups I and II and reduced in group III depending on alterations in serum potassium. Thus urinary diluting ability is reduced in renal transplant recipients due to a reduced glomerular filtration rate. The enhanced A II in hypertensive renal transplant recipients gives further evidence for the point of view that hypertension is angiotensin-dependent in most of these patients.

  10. Viral marketing

    OpenAIRE

    Král, Jiří

    2015-01-01

    Bachelor's Thesis deals with effective promotional tools called viral marketing. The main contribution of the thesis is the definition and history of viral marketing, making analysis of process of viral marketing, progresses definition and rules for creating a viral campaign. And also aspects are necessary for a successful viral spread. There are analysis of the characteristics of social media which are dividing according to the orientation and marketing tactics. Thesis is especially about so...

  11. A novel, Q-PCR based approach to measuring endogenous retroviral clearance by capture protein A chromatography.

    Science.gov (United States)

    Zhang, Min; Lute, Scott; Norling, Lenore; Hong, Connie; Safta, Aurelia; O'Connor, Deborah; Bernstein, Lisa J; Wang, Hua; Blank, Greg; Brorson, Kurt; Chen, Qi

    2009-04-01

    Quantification of virus removal by the purification process during production is required for clinical use of biopharmaceuticals. The current validation approach for virus removal by chromatography steps typically involves time-consuming spiking experiments with expensive model viruses at bench scale. Here we propose a novel, alternative approach that can be applied in at least one instance: evaluating retroviral clearance by protein A chromatography. Our strategy uses a quantitative PCR (Q-PCR) assay that quantifies the endogenous type C retrovirus-like particle genomes directly in production Chinese Hamster Ovary (CHO) cell culture harvests and protein A pools. This eliminates the need to perform spiking with model viruses, and measures the real virus from the process. Using this new approach, clearance values were obtained that was comparable to those from the old model-virus spike/removal approach. We tested the concept of design space for CHO retrovirus removal using samples from a protein A characterization study, where a wide range of chromatographic operating conditions were challenged, including load density, flow rate, wash, pooling, temperature, and resin life cycles. Little impact of these variables on CHO retrovirus clearance was found, arguing for implementation of the design space approach for viral clearance to support operational ranges and manufacturing excursions. The viral clearance results from Q-PCR were confirmed by an orthogonal quantitative product-enhanced reverse transcriptase (Q-PERT) assay that quantifies CHO retrovirus by their reverse transcriptase (RT) enzyme activity. Overall, our results demonstrate that protein A chromatography is a robust retrovirus removal step and CHO retrovirus removal can be directly measured at large scale using Q-PCR assays.

  12. Long-term risk of cervical intraepithelial neoplasia grade 3 or worse according to high-risk human papillomavirus genotype and semi-quantitative viral load among 33,288 women with normal cervical cytology

    DEFF Research Database (Denmark)

    Thomsen, Louise T; Frederiksen, Kirsten; Munk, Christian;

    2014-01-01

    In this prospective cohort study, we estimated the long-term risk of cervical intraepithelial neoplasia grade 3 or cancer (CIN3+) by high-risk human papillomavirus (hrHPV) genotype and semi-quantitative viral load at baseline among 33,288 women aged 14-90 years with normal baseline cytology. During...... 2002-2005, residual liquid-based cervical cytology samples were collected from women screened for cervical cancer in Copenhagen, Denmark. Samples were HPV-tested with Hybrid Capture 2 (HC2) and genotyped with INNO-LiPA. Semi-quantitative viral load was measured by HC2 relative light units in women......HPV genotyping during cervical cancer screening may help identify women at highest risk of CIN3+....

  13. Viral encephalitis

    Directory of Open Access Journals (Sweden)

    Marcus Tulius T Silva

    2013-09-01

    Full Text Available While systemic viral infections are exceptionally common, symptomatic viral infections of the brain parenchyma itself are very rare, but a serious neurologic condition. It is estimated that viral encephalitis occurs at a rate of 1.4 cases per 100.000 inhabitants. Geography is a major determinant of encephalitis caused by vector-borne pathogens. A diagnosis of viral encephalitis could be a challenge to the clinician, since almost 70% of viral encephalitis cases are left without an etiologic agent identified. In this review, the most common viral encephalitis will be discussed, with focus on ecology, diagnosis, and clinical management.

  14. Select neurocognitive impairment in HIV-infected women: associations with HIV viral load, hepatitis C virus, and depression, but not leukocyte telomere length.

    Directory of Open Access Journals (Sweden)

    Chantelle J Giesbrecht

    Full Text Available BACKGROUND: Through implementation of combination antiretroviral therapy (cART remarkable gains have been achieved in the management of HIV infection; nonetheless, the neurocognitive consequences of infection remain a pivotal concern in the cART era. Research has often employed norm-referenced neuropsychological scores, derived from healthy populations (excluding many seronegative individuals at high risk for HIV infection, to characterize impairments in predominately male HIV-infected populations. METHODS: Using matched-group methodology, we assessed 81 HIV-seropositive (HIV+ women with established neuropsychological measures validated for detection of HIV-related impairments, as well as additional detailed tests of executive function and decision-making from the Cambridge Neuropsychological Test Automated Battery (CANTAB. RESULTS: On validated tests, the HIV+ women exhibited impairments that were limited to significantly slower information processing speed when compared with 45 HIV-seronegative (HIV- women with very similar demographic backgrounds and illness comorbidities. Additionally, select executive impairments in shifting attention (i.e., reversal learning and in decision-making quality were revealed in HIV+ participants. Modifiers of neurocognition in HIV-infected women included detectable HIV plasma viral load, active hepatitis C virus co-infection, and self-reported depression symptoms. In contrast, leukocyte telomere length (LTL, a marker of cellular aging, did not significantly differ between HIV+ and HIV- women, nor was LTL associated with overall neurocognition in the HIV+ group. CONCLUSIONS: The findings suggest that well-managed HIV infection may entail a more circumscribed neurocognitive deficit pattern than that reported in many norm-referenced studies, and that common comorbidities make a secondary contribution to HIV-related neurocognitive impairments.

  15. Cumulative viral load and virologic decay patterns after antiretroviral therapy in HIV-infected subjects influence CD4 recovery and AIDS.

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    Vincent C Marconi

    Full Text Available BACKGROUND: The impact of viral load (VL decay and cumulative VL on CD4 recovery and AIDS after highly-active antiretroviral therapy (HAART is unknown. METHODS AND FINDINGS: Three virologic kinetic parameters (first year and overall exponential VL decay constants, and first year VL slope and cumulative VL during HAART were estimated for 2,278 patients who initiated HAART in the U.S. Military HIV Natural History Study. CD4 and VL trajectories were computed using linear and nonlinear Generalized Estimating Equations models. Multivariate Poisson and linear regression models were used to determine associations of VL parameters with CD4 recovery, adjusted for factors known to correlate with immune recovery. Cumulative VL higher than the sample median was independently associated with an increased risk of AIDS (relative risk 2.38, 95% confidence interval 1.56-3.62, p<0.001. Among patients with VL suppression, first year VL decay and slope were independent predictors of early CD4 recovery (p = 0.001 and overall gain (p<0.05. Despite VL suppression, those with slow decay during the first year of HAART as well as during the entire therapy period (overall, in general, gained less CD4 cells compared to the other subjects (133 vs. 195.4 cells/µL; p = 0.001 even after adjusting for potential confounders. CONCLUSIONS: In a cohort with free access to healthcare, independent of established predictors of AIDS and CD4 recovery during HAART, cumulative VL and virologic decay patterns were associated with AIDS and distinct aspects of CD4 reconstitution.

  16. Clinical Impact of Viral Load on the Development of Hepatocellular Carcinoma and Liver-Related Mortality in Patients with Hepatitis C Virus Infection

    Science.gov (United States)

    Noh, Ran; Lee, Doo Hyuck; Kwon, Byoung Woon; Kim, Yong Hyun

    2016-01-01

    Aim. This study aimed to assess clinical impact of hepatitis C viral load on the development of hepatocellular carcinoma (HCC) and liver-related mortality in HCV-infected patients. Methods. A total of 111 subjects with chronic HCV infection who were available for serum quantitation of HCV RNA were recruited in this retrospective cohort. Cox-proportional hazards models were used to calculate hazard ratio (HR) of developing HCC and liver-related mortality according to serum HCV RNA titers. Results. HCC was developed in 14 patients during follow-up period. The cumulative risk of HCC development was higher in subjects with high HCV RNA titer (log HCV RNA IU/mL > 6) than subjects with low titer (log HCV RNA IU/mL ≦ 6) (HR = 4.63, P = 0.032), giving an incidence rate of 474.1 and 111.5 per 10,000 person-years, respectively. Old age (HR = 9.71, P = 0.014), accompanying cirrhosis (HR = 19.34, P = 0.004), and low platelet count (HR = 13.97, P = 0.009) were other independent risk factors for the development of HCC. Liver-related death occurred in 7 patients. Accompanying cirrhosis (HR = 6.13, P = 0.012) and low albumin level (HR = 9.17, P = 0.002), but not HCV RNA titer, were significant risk factors related to liver-related mortality. Conclusion. Serum HCV RNA titer may be considered an independent risk factor for the development of HCC but not liver-related mortality. PMID:27656205

  17. Positive Predictive Value of the WHO Clinical and Immunologic Criteria to Predict Viral Load Failure among Adults on First, or Second-Line Antiretroviral Therapy in Kenya.

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    Anthony Waruru

    Full Text Available Routine HIV viral load (VL monitoring is the standard of care for persons receiving antiretroviral therapy (ART in developed countries. Although the World Health Organization recommends annual VL monitoring of patients on ART, recognizing difficulties in conducting routine VL testing, the WHO continues to recommend targeted VL testing to confirm treatment failure for persons who meet selected immunologic and clinical criteria. Studies have measured positive predictive value (PPV, negative predictive value, sensitivity and specificity of these criteria among patients receiving first-line ART but not specifically among those on second-line or subsequent regimens. Between 2008 and 2011, adult ART patients in Nyanza, Kenya who met national clinical or immunologic criteria for treatment failure received targeted VL testing. We calculated PPV and 95% confidence intervals (CI of these criteria to detect virologic treatment failure among patients receiving a first-line ART, b second/subsequent ART, and c any regimen. Of 12,134 patient specimens tested, 2,874 (23.7% were virologically confirmed as treatment failures. The PPV for 2,834 first-line ART patients who met either the clinical or immunologic criteria for treatment failure was 34.4% (95% CI 33.2-35.7, 33.1% (95% CI 24.7-42.3 for the 40 patients on second-line/subsequent regimens, and 33.4% (95% CI 33.1-35.6 for any ART. PPV, regardless of criteria, for first-line ART patients was lowest among patients over 44 years old and highest for patients aged 15 to 34 years. PPV of immunological and clinical criteria for correctly identifying treatment failure was similarly low for adult patients receiving either first-line or second-line/subsequent ART regimens. Our data confirm the inadequacy of clinical and immunologic criteria to correctly identify treatment failure and support the implementation of routine VL testing.

  18. Positive Predictive Value of the WHO Clinical and Immunologic Criteria to Predict Viral Load Failure among Adults on First, or Second-Line Antiretroviral Therapy in Kenya.

    Science.gov (United States)

    Waruru, Anthony; Muttai, Hellen; Ng'ang'a, Lucy; Ackers, Marta; Kim, Andrea; Miruka, Fredrick; Erick, Opiyo; Okonji, Julie; Ayuaya, Tolbert; Schwarcz, Sandra

    2016-01-01

    Routine HIV viral load (VL) monitoring is the standard of care for persons receiving antiretroviral therapy (ART) in developed countries. Although the World Health Organization recommends annual VL monitoring of patients on ART, recognizing difficulties in conducting routine VL testing, the WHO continues to recommend targeted VL testing to confirm treatment failure for persons who meet selected immunologic and clinical criteria. Studies have measured positive predictive value (PPV), negative predictive value, sensitivity and specificity of these criteria among patients receiving first-line ART but not specifically among those on second-line or subsequent regimens. Between 2008 and 2011, adult ART patients in Nyanza, Kenya who met national clinical or immunologic criteria for treatment failure received targeted VL testing. We calculated PPV and 95% confidence intervals (CI) of these criteria to detect virologic treatment failure among patients receiving a) first-line ART, b) second/subsequent ART, and c) any regimen. Of 12,134 patient specimens tested, 2,874 (23.7%) were virologically confirmed as treatment failures. The PPV for 2,834 first-line ART patients who met either the clinical or immunologic criteria for treatment failure was 34.4% (95% CI 33.2-35.7), 33.1% (95% CI 24.7-42.3) for the 40 patients on second-line/subsequent regimens, and 33.4% (95% CI 33.1-35.6) for any ART. PPV, regardless of criteria, for first-line ART patients was lowest among patients over 44 years old and highest for patients aged 15 to 34 years. PPV of immunological and clinical criteria for correctly identifying treatment failure was similarly low for adult patients receiving either first-line or second-line/subsequent ART regimens. Our data confirm the inadequacy of clinical and immunologic criteria to correctly identify treatment failure and support the implementation of routine VL testing.

  19. Apolipoprotein 4 may increase viral load and seizure frequency in mesial temporal lobe epilepsy patients with positive human herpes virus 6B.

    Science.gov (United States)

    Huang, Cheng; Yan, Bo; Lei, Ding; Si, Yang; Li, He; Chen, Ming-Wan; Li, Li; Chen, Fei; Zhou, Qiao; Zhou, Dong; Li, Jin-Mei

    2015-04-23

    This study investigated whether apolipoprotein 4 (ApoE4) was associated with the presence of human herpes virus (HHV)-6B in mesial temporal lobe epilepsy (MTLE). Polymerase chain reaction-restricted fragment length polymorphism (PCR-RFLP) was used to determine ApoE polymorphism in 46 patients with MTLE and 19 controls. Nested PCR and real-time PCR were applied to determine HHV-6B DNA and immunohistochemistry (IHC) for HHV-6B protein. Viral DNA load was significantly increased in MTLE patients with HHV-6B(+)/ApoE4 compared with those with HHV-6B(+)/non-ApoE4 (p=0.031). Semi-quantitative analysis of IHC showed significantly increased number of positive cells for HHV-6B proteins G116/64/54, P98 and U94 in patients with HHV-6B(+)/ApoE4 than HHV-6B(+)/non-ApoE4 (p=0.009, 0.035 and 0.009, respectively). Patients with HHV-6B(+)/ApoE4 showed higher seizure frequency than those with HHV-6B(+)/non-ApoE4 (p=0.005). There was no significant difference of ApoE alleles between MTLE with and without HHV-6B (p=0.115). ApoE4 was not associated with initial infection of HHV-6B in MTLE. However, ApoE4 may facilitate HHV-6B reactivation, DNA replication, virus protein expression and increase seizure frequency in MTLE. Further investigations are needed to understand the biomolecular mechanism underlying interaction between ApoE and HHV-6B.

  20. Regional differences in rates of HIV-1 viral load monitoring in Canada: Insights and implications for antiretroviral care in high income countries

    Directory of Open Access Journals (Sweden)

    Cooper Curtis

    2010-02-01

    Full Text Available Abstract Background Viral load (VL monitoring is an essential component of the care of HIV positive individuals. Rates of VL monitoring have been shown to vary by HIV risk factor and clinical characteristics. The objective of this study was to determine whether there are differences among regions in Canada in the rates of VL testing of HIV-positive individuals on combination antiretroviral therapy (cART, where the testing is available without financial barriers under the coverage of provincial health insurance programs. Methods The Canadian Observational Cohort (CANOC is a collaboration of nine Canadian cohorts of HIV-positive individuals who initiated cART after January 1, 2000. The study included participants with at least one year of follow-up. Generalized Estimating Equation (GEE regression models were used to determine the effect of geographic region on (1 the occurrence of an interval of 9 months or more between two consecutive recorded VL tests and (2 the number of days between VL tests, after adjusting for demographic and clinical covariates. Overall and regional annual rates of VL testing were also reported. Results 3,648 individuals were included in the analysis with a median follow-up of 42.9 months and a median of 15 VL tests. In multivariable GEE logistic regression models, gaps in VL testing >9 months were more likely in Quebec (Odds Ratio (OR = 1.72, p Conclusions Significant variation in rates of VL testing and the probability of a significant gap in testing were related to geographic region, HIV risk factor, age, year of cART initiation, type of cART regimen, being in the first year of cART, AIDS-defining illness and whether or not the previous VL was below the limit of detection.

  1. Increased cellular immune responses and CD4+ T-cell proliferation correlate with reduced plasma viral load in SIV challenged recombinant simian varicella virus - simian immunodeficiency virus (rSVV-SIV vaccinated rhesus macaques

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    Pahar Bapi

    2012-08-01

    Full Text Available Abstract Background An effective AIDS vaccine remains one of the highest priorities in HIV-research. Our recent study showed that vaccination of rhesus macaques with recombinant simian varicella virus (rSVV vector – simian immunodeficiency virus (SIV envelope and gag genes, induced neutralizing antibodies and cellular immune responses to SIV and also significantly reduced plasma viral loads following intravenous pathogenic challenge with SIVMAC251/CX1. Findings The purpose of this study was to define cellular immunological correlates of protection in rSVV-SIV vaccinated and SIV challenged animals. Immunofluorescent staining and multifunctional assessment of SIV-specific T-cell responses were evaluated in both Experimental and Control vaccinated animal groups. Significant increases in the proliferating CD4+ T-cell population and polyfunctional T-cell responses were observed in all Experimental-vaccinated animals compared with the Control-vaccinated animals. Conclusions Increased CD4+ T-cell proliferation was significantly and inversely correlated with plasma viral load. Increased SIV-specific polyfunctional cytokine responses and increased proliferation of CD4+ T-cell may be crucial to control plasma viral loads in vaccinated and SIVMAC251/CX1 challenged macaques.

  2. Viral marketing

    OpenAIRE

    BLÁHOVÁ, Adéla

    2012-01-01

    The aim of my thesis is to provide a comprehensive overview of the viral marketing and to analyze selected viral campaigns. There is a description of advantages and disadvantages of this marketing tool. In the end I suggest for which companies viral marketing is an appropriate form of the promotion.

  3. Spontaneous clearance of chronic hepatitis C infection is associated with an internal ribosomal entry site IIId stem loop structure variant

    Directory of Open Access Journals (Sweden)

    N G Bader El Din

    2015-01-01

    Full Text Available Aim: To investigate if any mutations in hepatitis C virus (HCV internal ribosome entry site (IRES can inhibit the translation of viral polyprotein. Materials and Methods: A 26-year-old male patient infected with HCV 10 years ago was followed up. After 9 years of chronic infection. The patient had managed to resolve the infection for a period of 9 months, after which the patient experienced a viral recurrence characterized by high viral load and diverse HCV quasispecies. The IRES structures of the viral strains that disappeared were comparable with those that are currently active using structural mutational analysis. Results: A novo mutational position 254 combined with a rarely observed mutation at position 253 in the stem of the IIId subdomain were observed and the new conformation had an octa-apical loop (AGUGUUGG and a shift in the 3 ` GU from the loop to the stem. Conclusions: These mutations were found to be highly deleterious, and they affected the direct binding of the IIId loop to the 40S ribosomal subunit with a subsequent inhibition of translation of viral polyprotein and clearance of the virus.

  4. Hepatitis C viral load does not predict disease outcome: going beyond numbers A carga viral do vírus da hepatite C não prediz a evolução: indo além dos números

    Directory of Open Access Journals (Sweden)

    Evaldo Stanislau Affonso de ARAÚJO

    2002-04-01

    Full Text Available The analysis of 58 patients with chronic hepatitis C without cirrhosis and treated with interferon-alpha demonstrated that hepatitis C viral (HCV load does not correlate with the histological evolution of the disease (p = 0.6559 for architectural alterations and p = 0.6271 for the histological activity index. Therefore, the use of viral RNA quantification as an evolutive predictor or determinant of the severity of hepatitis C is incorrect and of relative value. A review of the literature provided fundamental and interdependent HCV (genotype, heterogeneity and mutants, specific proteins, host (sex, age, weight, etc and treatment variables (dosage, time of treatment, type of interferon within the broader context of viral kinetics, interferon-mediated immunological response (in addition to natural immunity against HCV and the role of interferon as a modulator of fibrogenesis. Therefore, viral load implies much more than numbers and the correct interpretation of these data should consider a broader context depending on multiple factors that are more complex than the simple value obtained upon quantification.Através da análise de 58 pacientes tratados com Interferon Alfa em função de hepatite C crônica e sem cirrose, demonstramos que a carga viral do Vírus da Hepatite C (VHC não se correlacionou com a evolução histológica da doença (p = 0,6559 para alterações arquiteturais e p = 0,6271 para o Índice de Atividade Histológica-IAH. Assim a utilização da quantificação do RNA viral como preditor evolutivo ou determinante da gravidade da hepatite C é incorreto e de valor relativo. Revisando o tema encontramos variáveis do VHC (genótipo, heterogeneidade e mutantes, proteínas específicas, do hospedeiro (sexo, idade, peso, etc e dos medicamentos (posologia, tempo de tratamento, tipo de Interferon fundamentais e interdependentes, inseridas no contexto mais amplo da cinética viral, da resposta imunológica mediada pelo Interferon (al

  5. Simplified clinical prediction scores to target viral load testing in adults with suspected first line treatment failure in Phnom Penh, Cambodia.

    Directory of Open Access Journals (Sweden)

    Johan van Griensven

    Full Text Available BACKGROUND: For settings with limited laboratory capacity, 2013 World Health Organization (WHO guidelines recommend targeted HIV-1 viral load (VL testing to identify virological failure. We previously developed and validated a clinical prediction score (CPS for targeted VL testing, relying on clinical, adherence and laboratory data. While outperforming the WHO failure criteria, it required substantial calculation and review of all previous laboratory tests. In response, we developed four simplified, less error-prone and broadly applicable CPS versions that can be done 'on the spot'. METHODOLOGY/PRINCIPAL: Findings From May 2010 to June 2011, we validated the original CPS in a non-governmental hospital in Phnom Penh, Cambodia applying the CPS to adults on first-line treatment >1 year. Virological failure was defined as a single VL >1000 copies/ml. The four CPSs included CPS1 with 'current CD4 count' instead of %-decline-from-peak CD4; CPS2 with hemoglobin measurements removed; CPS3 having 'decrease in CD4 count below baseline value' removed; CPS4 was purely clinical. Score development relied on the Spiegelhalter/Knill-Jones method. Variables independently associated with virological failure with a likelihood ratio ≥ 1.5 or ≤ 0.67 were retained. CPS performance was evaluated based on the area-under-the-ROC-curve (AUROC and 95% confidence intervals (CI. The CPSs were validated in an independent dataset. A total of 1490 individuals (56.6% female, median age: 38 years (interquartile range (IQR 33-44; median baseline CD4 count: 94 cells/µL (IQR 28-205, median time on antiretroviral therapy 3.6 years (IQR 2.1-5.1, were included. Forty-five 45 (3.0% individuals had virological failure. CPS1 yielded an AUROC of 0.69 (95% CI: 0.62-0.75 in validation, CPS2 an AUROC of 0.68 (95% CI: 0.62-0.74, and CPS3, an AUROC of 0.67 (95% CI: 0.61-0.73. The purely clinical CPS4 performed poorly (AUROC-0.59; 95% CI: 0.53-0.65. CONCLUSIONS: Simplified CPSs retained

  6. Transmitted drug resistance in the CFAR network of integrated clinical systems cohort: prevalence and effects on pre-therapy CD4 and viral load.

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    Art F Y Poon

    Full Text Available Human immunodeficiency virus type 1 (HIV-1 genomes often carry one or more mutations associated with drug resistance upon transmission into a therapy-naïve individual. We assessed the prevalence and clinical significance of transmitted drug resistance (TDR in chronically-infected therapy-naïve patients enrolled in a multi-center cohort in North America. Pre-therapy clinical significance was quantified by plasma viral load (pVL and CD4+ cell count (CD4 at baseline. Naïve bulk sequences of HIV-1 protease and reverse transcriptase (RT were screened for resistance mutations as defined by the World Health Organization surveillance list. The overall prevalence of TDR was 14.2%. We used a Bayesian network to identify co-transmission of TDR mutations in clusters associated with specific drugs or drug classes. Aggregate effects of mutations by drug class were estimated by fitting linear models of pVL and CD4 on weighted sums over TDR mutations according to the Stanford HIV Database algorithm. Transmitted resistance to both classes of reverse transcriptase inhibitors was significantly associated with lower CD4, but had opposing effects on pVL. In contrast, position-specific analyses of TDR mutations revealed substantial effects on CD4 and pVL at several residue positions that were being masked in the aggregate analyses, and significant interaction effects as well. Residue positions in RT with predominant effects on CD4 or pVL (D67 and M184 were re-evaluated in causal models using an inverse probability-weighting scheme to address the problem of confounding by other mutations and demographic or risk factors. We found that causal effect estimates of mutations M184V/I (-1.7 log₁₀pVL and D67N/G (-2.1[³√CD4] and 0.4 log₁₀pVL were compensated by K103N/S and K219Q/E/N/R. As TDR becomes an increasing dilemma in this modern era of highly-active antiretroviral therapy, these results have immediate significance for the clinical management of HIV-1

  7. Should viral load thresholds be lowered?: Revisiting the WHO definition for virologic failure in patients on antiretroviral therapy in resource-limited settings.

    Science.gov (United States)

    Labhardt, Niklaus D; Bader, Joëlle; Lejone, Thabo Ishmael; Ringera, Isaac; Hobbins, Michael A; Fritz, Christiane; Ehmer, Jochen; Cerutti, Bernard; Puga, Daniel; Klimkait, Thomas

    2016-07-01

    The World Health Organization (WHO) guidelines on antiretroviral therapy (ART) define treatment failure as 2 consecutive viral loads (VLs) ≥1000 copies/mL. There is, however, little evidence supporting 1000 copies as an optimal threshold to define treatment failure. Objective of this study was to assess the correlation of the WHO definition with the presence of drug-resistance mutations in patients who present with 2 consecutive unsuppressed VL in a resource-limited setting.In 10 nurse-led clinics in rural Lesotho children and adults on first-line ART for ≥6 months received a first routine VL. Those with plasma VL ≥80 copies/mL were enrolled in a prospective study, receiving enhanced adherence counseling (EAC) and a follow-up VL after 3 months. After a second unsuppressed VL genotypic resistance testing was performed. Viruses with major mutations against ≥2 drugs of the current regimen were classified as "resistant".A total of 1563 adults and 191 children received a first routine VL. Of the 138 adults and 53 children with unsuppressed VL (≥80 copies/mL), 165 (116 adults; 49 children) had a follow-up VL after EAC; 108 (74 adults; 34 children) remained unsuppressed and resistance testing was successful. Ninety of them fulfilled the WHO definition of treatment failure (both VL ≥1000 copies/mL); for another 18 both VL were unsuppressed but with definition was 81.1% (73/90) for the presence of resistant virus. Among the 18 with VL levels between 80 and 1000 copies/mL, thereby classified as "non-failures", 17 (94.4%) harbored resistant viruses. Lowering the VL threshold from 1000 copies/mL to 80 copies/mL at both determinations had no negative influence on the PPV (83.3%; 90/108).The current WHO-definition misclassifies patients who harbor resistant virus at VL below 1000 c/mL as "nonfailing." Lowering the threshold to VL ≥80 copies/mL identifies a significantly higher number of patients with treatment-resistant virus and should be

  8. 艾滋病患者外周血病毒载量检出的影响因素分析%Analysis of Influencing Factors of Detection of Peripheral Blood Viral Load in AIDS Patients

    Institute of Scientific and Technical Information of China (English)

    刘会娟; 张肖肖; 蒋自强

    2012-01-01

    目的 从临床角度探讨艾滋病患者外周血病毒载量检出的影响因素,为临床治疗提供依据.方法 收集2010年以来我们中心开展的课题资料的人口学信息、实验室血常规、免疫学指标(CD+4T细胞计数、CD+8T细胞计数)及病毒载量检测值,影响因素分析采用Logistic回归.结果 纳入分析146例资料,其中89例外周血病毒载量<40 copys/ml(未检出组),57例外周血病毒载量≥40 copys/ml(检出组).Logistic回归分析最终纳入3个影响病毒载量是否检测出的主要因素,分别为较低年龄分段(<30岁,OR=15.875,P=0.001;30~39岁,OR=6.317,P=0.002;40~49岁,OR=2.387,P=0.129)、确认年限(OR=2.251,P=0.038)和CD+4T细胞计数分段(OR=0.382,P=0.014).结论 艾滋病患者外周血病毒载量是否检出的影响因素有确认时间、年龄分段和CD+4T细胞计数.%Objective To explore the factors influencing detection of peripheral blood viral load to provide a basis for its clinical treatment. Methods Demographic information, laboratory routine blood, immunological indexes ( CD/ T cell count, CD8+ T cell count ) and viral load assessment were collected from the subject data of AIDS Treatment and Research Center. Logistic regression analysis was carried out on influencing factors on level of viral load. Results A total of 146 cases were chosen for analysis, including 89 with a peripheral blood viral load <40 copys/ml ( un -detection group ) and 57 with load ≥40 copys/ml ( detection group ). Logistic regression analysis finally enrolled 3 main factors influencing viral load detection, including lower age segmentation ( <30yearsold, OR = 15.875, P=0.001; 30 ~ 39 years old, OR=6.317, P=0.002; 39-49 years old, OR=2.387, P=0.129), time confirmation ( OR = 2. 251, P = 0. 038 ) and CD4+ T cell count ( OR = 0. 382, P=0.014). Conclusion The factors influencing detection of peripheral blood viral load are time conformation, age segments and CD/ T cell count.

  9. CD4 cell count and the risk of AIDS or death in HIV-Infected adults on combination antiretroviral therapy with a suppressed viral load: a longitudinal cohort study from COHERE.

    Directory of Open Access Journals (Sweden)

    Jim Young

    Full Text Available BACKGROUND: Most adults infected with HIV achieve viral suppression within a year of starting combination antiretroviral therapy (cART. It is important to understand the risk of AIDS events or death for patients with a suppressed viral load. METHODS AND FINDINGS: Using data from the Collaboration of Observational HIV Epidemiological Research Europe (2010 merger, we assessed the risk of a new AIDS-defining event or death in successfully treated patients. We accumulated episodes of viral suppression for each patient while on cART, each episode beginning with the second of two consecutive plasma viral load measurements 500 copies/µl, the first of two consecutive measurements between 50-500 copies/µl, cART interruption or administrative censoring. We used stratified multivariate Cox models to estimate the association between time updated CD4 cell count and a new AIDS event or death or death alone. 75,336 patients contributed 104,265 suppression episodes and were suppressed while on cART for a median 2.7 years. The mortality rate was 4.8 per 1,000 years of viral suppression. A higher CD4 cell count was always associated with a reduced risk of a new AIDS event or death; with a hazard ratio per 100 cells/µl (95% CI of: 0.35 (0.30-0.40 for counts <200 cells/µl, 0.81 (0.71-0.92 for counts 200 to <350 cells/µl, 0.74 (0.66-0.83 for counts 350 to <500 cells/µl, and 0.96 (0.92-0.99 for counts ≥500 cells/µl. A higher CD4 cell count became even more beneficial over time for patients with CD4 cell counts <200 cells/µl. CONCLUSIONS: Despite the low mortality rate, the risk of a new AIDS event or death follows a CD4 cell count gradient in patients with viral suppression. A higher CD4 cell count was associated with the greatest benefit for patients with a CD4 cell count <200 cells/µl but still some slight benefit for those with a CD4 cell count ≥500 cells/µl.

  10. Interleukin-27 is differentially associated with HIV viral load and CD4+ T cell counts in therapy-naive HIV-mono-infected and HIV/HCV-co-infected Chinese.

    Directory of Open Access Journals (Sweden)

    Lai He

    Full Text Available Human Immunodeficiency Virus (HIV infection and the resultant Acquired Immunodeficiency Syndrome (AIDS epidemic are major global health challenges; hepatitis C virus (HCV co-infection has made the HIV/AIDS epidemic even worse. Interleukin-27 (IL-27, a cytokine which inhibits HIV and HCV replication in vitro, associates with HIV infection and HIV/HCV co-infection in clinical settings. However, the impact of HIV and HCV viral loads on plasma IL-27 expression levels has not been well characterized. In this study, 155 antiretroviral therapy-naïve Chinese were recruited. Among them 80 were HIV- and HCV-negative healthy controls, 45 were HIV-mono-infected and 30 were HIV/HCV-co-infected. Plasma level HIV, HCV, IL-27 and CD4+ number were counted and their correlation, regression relationships were explored. We show that: plasma IL-27 level was significantly upregulated in HIV-mono-infected and HIV/HCV-co-infected Chinese; HIV viral load was negatively correlated with IL-27 titer in HIV-mono-infected subjects whereas the relationship was opposite in HIV/HCV-co-infected subjects; and the relationships between HIV viral loads, IL-27 titers and CD4+ T cell counts in the HIV mono-infection and HIV/HCV co-infection groups were dramatically different. Overall, our results suggest that IL-27 differs in treatment-naïve groups with HIV mono-infections and HIV/HCV co-infections, thereby providing critical information to be considered when caring and treating those with HIV mono-infection and HIV/HCV co-infection.

  11. [Analysis of the results of the 2010 External Quality Control Program of the Spanish Society of Infectious Diseases and Clinical Microbiology for HIV-1, HCV, and HBV viral loads].

    Science.gov (United States)

    Orta Mira, Nieves; Serrano, María del Remedio Guna; Martínez, José-Carlos Latorre; Ovies, María Rosario; Poveda, Marta; de Gopegui, Enrique Ruiz; Cardona, Concepción Gimeno

    2011-12-01

    Human immunodeficiency virus type 1 (HIV-1) and hepatitis B (HBV) and C virus (HCV) viral load determinations are among the most important markers for the follow-up of patients infected with these viruses. External quality control tools are crucial to ensure the accuracy of the results obtained by microbiology laboratories. This article summarized the results obtained in the 2010 External Quality Control Program of the Spanish Society of Infectious Diseases and Clinical Microbiology for HIV-1, HCV, and HBV viral loads and HCV genotyping. In the HIV-1 program, a total of five standards were sent. One standard consisted of seronegative human plasma, while the remaining four contained plasma from three different viremic patients, in the range of 3-5 log(10) copies/mL; two of these standards were identical, with the aim of determining repeatability. A significant proportion of the laboratories (22.6% on average) obtained values out of the accepted range (mean ± 0.2 log(10)copies/mL), depending on the standard and on the method used for quantification. Repeatability was very good, with up to 95% of laboratories reporting results within the limits (Δ<0.5 log(10)copies/mL). The HBV and HCV program consisted of two standards with different viral load contents. Most of the participants, 86.1% in the case of HCV and 87.1% in HBV, obtained all the results within the accepted range (mean ± 1.96 SD log(10)UI/mL). Post-analytical errors due to mistranscription of the results were detected in these controls. Data from this analysis reinforce the utility of proficiency programs to ensure the quality of the results obtained by a particular laboratory, as well as the importance of the post-analytical phase in overall quality. Due to interlaboratory variability, use of the same method and the same laboratory for patient follow-up is advisable.

  12. 宫颈癌不同治疗方法对HPV病毒载量的影响%Effects of different therapeutic methods of cervical cancer on viral load of HPV

    Institute of Scientific and Technical Information of China (English)

    陈红香; 白生宾; 玛依努尔·尼牙孜; 夏小艳

    2011-01-01

    Objective: To explore the effects of different therapeutic methods of cervical cancer with different clinical stages and grades of differentiation on viral load of human papillomavirus (HPV) . Methods: 227 cases with squamous cell carcinoma of cervix treated in the hospital from January 2007 to January 2010 were selected as study objects, then they were divided into radical surgery group, radical radiotherapy group and radical radiotherapy plus chemotherapy group according to clinical stages; the cervical secretions on admission and after treatment were collected; hybrid capture Ⅱ method was used to detect viral load of HPV. Results: The infection rate of HPV was 99. 11%, after treatment, the infection rate of HPV was 57. 26%; there was significant difference in viral load of HPV among different clinical stages ( P < 0. 05 ), there was no significant difference in viral load of HPV between cervical cancer of high differentiation and cervical cancer of middle differentiation ( P > 0. 05 ), but there was significant difference in viral load of HPV between cervical cancer of middle differentiation and cervical cancer of low differentiation, cervical cancer of high differentiation and cervical cancer of low differentiation (P <0. 05 ); there was significant difference in viral load of HPV among radical surgery group, radical radiotherapy group and radical radiotherapy plus chemotherapy group (P < 0. 05 ) . Conclusion: Cervical cancer with high FIGO stages has low differentiation and high viral load of HPV, radical surgery and radical surgery combined with radiotherapy and chemotherapy may reduce the viral load of HPV significantly, detection of viral load of HPV can be used as a marker of screening of cervical cancer and follow - up and monitoring of the disease.%目的:探讨不同分期及组织分化的宫颈癌患者HPV病毒载量及宫颈癌不同治疗方案对HPV病毒载量的影响.方法:以2007年1月~2010年1月新疆维吾尔自治区人

  13. Effectiveness of first-line antiretroviral therapy based on NNRTIs vs ritonavir-boosted PIs in HIV-1 infected patients with high plasma viral load

    Directory of Open Access Journals (Sweden)

    A Imaz

    2012-11-01

    Full Text Available Purpose of the study: Few clinical trials have compared non-nucleoside reverse transcriptase inhibitors (NNRTI and ritonavir-boosted protease inhibitors (PI/r as initial combined antiretroviral therapy (cART for HIV-1-infected patients with high plasma viral load (pVL, and non-conclusive results have been reported. We compared the effectiveness between NNRTI and PI/r as first-line cART for HIV-1-infected patients with high pVL. Methods: Observational retrospective study of 664 consecutive treatment-naïve HIV-1-infected patients with pVL (HIV-1 RNA >100,000 copies/mL who initiated NNRTI or PI/r-based cART between 2000–2010 in three University hospitals. Only currently preferred or alternative regimens in clinical guidelines were included. Primary endpoint: percentage of therapeutic failures at week 48. Virologic failure was defined as: a lack of virologic response (<1 log RNA HIV-1 decrease in first 3 months; b RNA HIV-1 >50 c/mL at week 48; c confirmed rebound >50 c/ml after a previous value <50 c/mL. Intent-to-treat (ITT noncompleter=failure and on-treatment (OT analyses were performed. Results: 62% of patients initiated NNRTI-regimens (83% efavirenz and 38% PI/r-regimens (62% lopinavir/. Baseline characteristics: male 83%; median age 39 yrs; median CD4 count: 212/µL (NNRTI 232 vs PI/r 177, p=0.028; pVL 5.83 log10 c/mL (NNRTI 5.43 vs PI/r 5.55, p=0.007; AIDS 24% (NNRTI 21% vs PI/r 29%, p=0.015. NRTI backbones were tenofovir plus 3TC or FTC in 72%. The percentage of therapeutic failure was higher in the PI/r group (ITT NC=F 26% vs 18%, p=0.012 with no differences in virologic failures (PI/r 5%, NNRTI 6%, p=0.688. The rate of treatment changes due to toxicity and/or voluntary discontinuations was higher in the PI/r group (15% vs 8%, p=0.008. A multivariate analysis adjusted for age, gender, CD4 count, VL and AIDS showed NNRTI vs PI/r as the only variable associated with treatment response (OR 0.61, 95% CI 0.41–0.88. Median pVL and rate of

  14. Effect of cytokine gene polymorphism on histological activity index, viral load and response to treatment in patients with chronic hepatitis C genotype 3

    Institute of Scientific and Technical Information of China (English)

    Zaigham Abbas; Tariq Moatter; Akber Hussainy; Wasim Jafri

    2005-01-01

    levels were not significantly different among different cytokine polymorphisms. There was a significant correlation of HAI and HCV RNA levels with the duration of disease. TGFβ -10 genotype CC patients had a better end of treatment response than those with other genotypes (P = 0.020). Sustained virological response to the treatment was not influenced by the cytokine polymorphism. No effect of other factors like viral load,degree of fibrosis, gender, steatosis, was observed on sustained virological response in this population infected with genotype 3.CONCLUSION: There is no significant correlation between cytokine polymorphisms and HAI except for the polymorphisms of anti-inflammatory cytokine IL-10,which may influence hepatic inflammatory activity and fibrosis in patients with chronic hepatitis C genotype 3.Sustained virological response in this genotype does not seem to be influenced by cytokine gene polymorphisms.

  15. Switching to nevirapine-based regimens after undetectable viral load is not associated with increased risk of discontinuation due to toxicity

    Directory of Open Access Journals (Sweden)

    Patricia Patterson

    2014-11-01

    Full Text Available Introduction: Due to its good tolerability, favourable cardiovascular risk-profile, low-pill burden and cost, nevirapine-based regimens are an attractive simplification strategy for patients with suppressed viral load (VL. However, current guidelines recommend caution if nevirapine (NVP is prescribed in males and females with CD4 counts above 400 or 250 cells/µL, respectively. The aim of this study is to determine the prevalence and risk factors associated with development of toxicity or treatment discontinuation in patients switching to NVP-based regimens. Materials and Methods: Retrospective chart review of HIV-infected patients with suppressed VL who switched from a PI-based regimen to a NVP-based regimen in four HIV clinics in Argentina, between 1997 and 2013. Bivariate and multivariate analyses were performed to explore factors associated with treatment discontinuation. High CD4 count was defined as CD4-cell count ≥400 or 250 cells/µL in males and females, respectively. Results: Of 218 patients included, 165 (75.7% were male; 21 (9.6% were co-infected with HCV and/or HBV. Median baseline (BSL CD4 count: 138 cells/µL (IQR: 64–276. At switch, patients had a median age of 38 years (IQR: 33.4–43.8 and had been suppressed for a median of 1.4 years (IQR: 0.6–2.2; 138 patients (63.3% had high CD4-cell counts: among females, median CD4 count at switch was 462 (IQR: 330–709 cells/µL; among males, 433 (IQR: 305–595 cells/µL. Thirty-six patients (13.5% presented NVP-related toxicity (30 skin toxicity, 6 hepatic toxicity, 29 (13.3% discontinued NVP. Median time to development to toxicity: 32 days (IQR: 15–75. In bivariate analysis, chronic hepatitis was the only variable associated with development of toxicity (OR: 2.90, 95% CI 1.08–7.78. In multivariate analysis, no statistical significant associations were observed between either development of toxicity or treatment discontinuation and gender, chronic hepatitis, age or CD4-cell

  16. Treatment-associated polymorphisms in protease are significantly associated with higher viral load and lower CD4 count in newly diagnosed drug-naive HIV-1 infected patients

    NARCIS (Netherlands)

    K. Theys (Kristof); K. Deforche; J. Vercauteren (Jurgen); P. Libin (Pieter); D.A.M.C. van de Vijver (David); J. Albert (Jan); B. Åsjö (Birgitta); M. Bruckova (Marie); R.J. Camacho (Ricardo Jorge); B. Clotet (Bonaventura); Z. Grossman (Zehava); A. Horban (Andrzej); C. Kücherer (Claudia); D. Paraskevis (Dimitrios); E. Puchhammer-Stöckl (Elisabeth); C. Riva (Chiara); L. Ruiz (Lidia); J.-C. Schmit (Jean-Claude); R. Schuurman (Rob); A. Sonnerborg (Anders); D. Stanekova (Danica); D. Struck (Daniel); K. van Laethem (Kristel); A.M.J. Wensing (Annemarie); E. Puchhammer-Stockl E. (E.); M. Sarcletti (M.); B. Schmied (B.); M. Geit (M.); G. Balluch (G.); A.M. Vandamme (Anne Mieke); I. Derdelinck (Inge); A. Sasse (A.); M. Bogaert (M.); H. Ceunen (H.); A. de Roo (Annie); M. De Wit (Meike); F. Echahidi (F.); K. Fransen (K.); J.-C. Goffard (J.); P. Goubau (Patrick); E. Goudeseune (E.); J.-C. Yombi (J.); P. Lacor (Patrick); C. Liesnard (C.); M. Moutschen (M.); L.A. Pierard; R. Rens (R.); J. Schrooten; D. Vaira (D.); A. van den Heuvel (A.); B. van der Gucht (B.); M. van Ranst (Marc); E. van Wijngaerden (Eric); T. Vandercam; M. Vekemans (M.); C. Verhofstede; N. Clumeck (N.); K. van Laethem (K.); L.G. Kostrikis (Leondios); I. Demetriades (I.); I. Kousiappa (Ioanna); V.L. Demetriou (Victoria); J. Hezka (Johana); M. Linka (Marek); L. Machala (L.); L.B. Jrgensen (L.); J. Gerstoft (J.); L. Mathiesen (L.); C. Pedersen (Court); C. Nielsen (Claus); A. Laursen (A.); B. Kvinesdal (B.); K. Liitsola (Kirsi); M. Ristola (M.); J. Suni (J.); J. Sutinen (J.); K. Korn (Klaus); C. K̈ucherer (C.); P. Braun (P.); G. Poggensee (G.); M. Däumer (M.); D. Eberle (David); O. Hamouda (Osamah); H. Heiken (H.); R. Kaiser (R.); H. Knechten (H.); H. M̈uller (H.); S. Neifer (S.); H. Walter (Hauke); B. Gunsenheimer-Bartmeyer (B.); T. Harrer (T.); A. Hatzakis (Angelos); E. Hatzitheodorou (E.); C. Issaris (C.); C. Haida (C.); A. Zavitsanou (A.); G. Magiorkinis (Gkikas); M. Lazanas (M.); L. Chini; N. Magafas (N.); N. Tsogas (N.); V. Paparizos (V.); S. Kourkounti (S.); A. Antoniadou (A.); A. Papadopoulos (A.); P. Panagopoulos (P.); G. Poulakou (G.); V. Sakka (V.); G. Chryssos (G.); S. Drimis (S.); P. Gargalianos (P.); M. Lelekis (M.); G. Xilomenos (G.); M. Psichogiou (M.); G.L. Daikos (G.); G. Panos (G.); G. Haratsis (G.); T. Kordossis (T.); A. Kontos (Angelos); G. Koratzanis (G.); M. Theodoridou (M.); G. Mostrou (G.); V. Spoulou (V.); W. Hall (W.); C. de Gascun (Cillian); C. Byrne (C.); M. Duffy (M.); P. Bergin; D. Reidy (D.); G. Farrell; J. Lambert (Julien); E. O'Connor (E.); A. Rochford (A.); J. Low (J.); P. Coakely (P.); S. Coughlan (Suzie); I. Levi (I.); D. Chemtob (D.); C. Balotta (Claudia); C. Mussini (C.); I. Caramma (I.); A. Capetti (A.); M.C. Colombo (M.); C. Rossi (Cesare); F. Prati (Francesco); F. Tramuto (F.); F. Vitale (F.); M. Ciccozzi (M.); G. Angarano (Guiseppe); G. Rezza (G.); R. Hemmer (R.); V. Arendt (V.); T. Staub (T.); F. Schneider (F.); F. Roman (Francois); C.A. Boucher (Charles); P.H.M. van Bentum (P. H M); K. Brinkman; E.L.M. Op de Coul (Eline); M.E. van der Ende (Marchina); I.M. Hoepelman (Ilja Mohandas); M.E.E. van Kasteren (Marjo); J. Juttmann (Job); M. Kuipers (M.); N. Langebeek (Nienke); C. Richter (C.); R.M.W.J. Santegoets (R. M W J); L. Schrijnders-Gudde (L.); R. Schuurman (R.); B.J.M. van de Ven (B. J M); B. Asjö (Birgitta); V. Ormaasen (Vidar); P. Aavitsland (P.); J. Stanczak (J.); G.P. Stanczak (G.); E. Firlag-Burkacka (E.); A. Wiercinska-Drapalo (A.); E. Jablonowska (E.); E. Malolepsza (E.); M. Leszczyszyn-Pynka (M.); W. Szata (W.); A. de Palma (Andre); F. Borges (F.); T. Paix̃ao (T.); V. Duque (V.); F. Aráujo (F.); M. Stanojevic (Maja); D.J. Jevtovic (D.); D. Salemovic (D.); M. Habekova (M.); M. Mokras (M.); P. Truska (P.); M. Poljak (Mario); D. Babic (D.); J. Tomazic (J.); S. Vidmar (Suzanna); P. Karner (P.); C. Gutíerrez (C.); C. deMendoza (C.); I. Erkicia (I.); P. Domingo (P.); X. Camino (X.); M.A. Galindo (Miguel Angel); J.L. Blanco (J.); M. Leal (M.); A. Masabeu (A.); A. Guelar (A.); J.M. Llibre (Josep M.); N. Margall (N.); C. Iribarren (Carlos); S. Gutierrez (S.); J.F. Baldov́i (J.); C.E. Pedreira (Carlos Eduardo); J.M. Gatell (J.); S. Moreno (S.); C. de Mendoza (Carmen); V. Soriano (Virtudes); A. Blaxhult (A.); A. Heidarian (A.); A. Karlsson (A.); K. Aperia-Peipke (K.); I.-M. Bergbrant (I.); M. Gissĺen (M.); M. Svennerholm (M.); P. Bj̈orkman (P.); G. Bratt (G.); M. Carlsson (M.); H. Ekvall (H.); M. Ericsson (M.); M. Ḧofer (M.); B. Johansson (Bert); N. Kuylenstierna (N.); K. Ljungberg (Karl); S. Mäkitalo (S.); A. Strand; K. Öberg (Kjell); T. Berg (Trine)

    2012-01-01

    textabstractBackground: The effect of drug resistance transmission on disease progression in the newly infected patient is not well understood. Major drug resistance mutations severely impair viral fitness in a drug free environment, and therefore are expected to revert quickly. Compensatory mutatio

  17. Relação entre diagnóstico citopatológico de neoplasia intra-epitelial cervical e índices de células CD4+ e de carga viral em pacientes HIV-soropositivas Association of cervical intraepithelial neoplasia with CD4 T cell counts and viral load in HIV-infected women

    Directory of Open Access Journals (Sweden)

    Raquel Autran Coelho

    2004-03-01

    -RNA viral load in HIV-positive patients. METHODS: one hundred and fifteen HIV patients were evaluated retrospectively in the present study, during the period from January 2002 to April 2003, at a university hospital. Eighty-three patients presented cervical intraepithelial neoplasia (CIN in Pap smear, in comparison with thirty-two with no lesions. Patients were divided into three groups, according to CD4 counts: CD4 more than 500 cells/mm³, between 200 and 500 cells/mm³, and less than 200 cells/mm³, and other three groups, according to HIV viral load: less than 10,000 HIV-RNA copies/mL, between 10,000 and 100,000 HIV-RNA copies/mL, or more than 100,000 HIV-RNA copies/mL. Correlation was investigated by the Fisher test. RESULTS: of the eighty-three patients with CIN, 73% presented CD4 counts less than 500 cells/mm³. In all CD4 groups, more than 50% of the patients presented CIN. According to the viral load, 71.7% of the patients with less than 10,000 HIV-RNA copies/mL presented CIN I, compared with 11.3% that showed CIN III. In the group with higher viral load (>100.000 HIV-RNA copies/mL, 61.5% showed CIN I and 30.8% presented CIN III. CONCLUSION: association between viral load and CIN was established (p=0.013, which was not observed with CD4 cell counts and CIN. Concomitant cervicovaginal infection was considered a potential confounding factor.

  18. Viral information.

    Science.gov (United States)

    Rohwer, Forest; Barott, Katie

    2013-03-01

    Viruses are major drivers of global biogeochemistry and the etiological agents of many diseases. They are also the winners in the game of life: there are more viruses on the planet than cellular organisms and they encode most of the genetic diversity on the planet. In fact, it is reasonable to view life as a viral incubator. Nevertheless, most ecological and evolutionary theories were developed, and continue to be developed, without considering the virosphere. This means these theories need to be to reinterpreted in light of viral knowledge or we need to develop new theory from the viral point-of-view. Here we briefly introduce our viral planet and then address a major outstanding question in biology: why is most of life viral? A key insight is that during an infection cycle the original virus is completely broken down and only the associated information is passed on to the next generation. This is different for cellular organisms, which must pass on some physical part of themselves from generation to generation. Based on this premise, it is proposed that the thermodynamic consequences of physical information (e.g., Landauer's principle) are observed in natural viral populations. This link between physical and genetic information is then used to develop the Viral Information Hypothesis, which states that genetic information replicates itself to the detriment of system energy efficiency (i.e., is viral in nature). Finally, we show how viral information can be tested, and illustrate how this novel view can explain existing ecological and evolutionary theories from more fundamental principles.

  19. Mutations in carboxy-terminal part of E2 including PKR/eIF2αphosphorylation homology domain and interferon sensitivity determining region of nonstructural 5A of hepatitis C virus 1b:Their correlation with response to interferon monotherapy and viral load

    Institute of Scientific and Technical Information of China (English)

    Koji Ukai; Masatoshi Ishigami; Kentaro Yoshioka; Naoto Kawabe; Yoshiaki Katano; Kazuhiko Hayashi; Takashi Honda; Motoyoshi Yano; Hidemi Goto

    2006-01-01

    AIM: To study the amino acid substitutions in the carboxy (C)-terminal part of E2 protein and in the interferon (IFN) sensitivity determining region (ISDR)and their correlation with response to IFN and viral load in 85 hepatitis C virus (HCV)-1b-infected patients treated with IFN.METHODS: The C-terminal part of E2 (codons 617-711)including PKR/eIF2α phosphorylation homology domain (PePHD) and ISDR was sequenced in 85 HCV-1b-infected patients treated by IFN monotherapy.RESULTS: The amino acid substitutions in PePHD detected only in 4 of 85 patients were not correlated either with response to IFN or with viral load. The presence of substitutions in a N-terminal variable region (codons 617-641) in the C-terminal part of E2was significantly correlated with both small viral load (33.9% vs 13.8%, P=0.0394) and sustained response to IFN (25.0% vs 6.9%,P=0.0429). Four or more substitutions in ISDR were significantly correlated with both small viral load (78.6% vs 16.2%, P<0.0001) and sustained response to IFN (85.7% vs 2.9%, P<0.0001).In multivariate analysis, ISDR in nonstructural (NS) 5A (OR=0.39, P<0.0001) and N-terminal variable region (OR=0.51, P=0.039) was selected as the independent predictors for small viral load, and ISDR (OR=39.0, P<0.0001) was selected as the only independent predictor for sustained response.CONCLUSION: The N-terminal variable region in the C-terminal part of E2 correlates with both response to IFN monotherapy and viral load and is one of the factors independently associated with a small viral load.

  20. VIRAL MARKETING

    OpenAIRE

    OLENTSOVA Y.A.

    2016-01-01

    Abstract This project seeks to investigate how the company Gitz can create awareness towards their brand by using viral marketing. To do this we analyze which elements of viral marketing the company can use, to reach their goal. In order to utilize the selected tools of viral marketing best possible, we need to figure out the company’s customer segment and figure out how to reach that segment. This has been done with the use of Henrik Dahl’s Minerva-model that divides the population into f...

  1. Hepatitis C viral load, genotype 3 and interleukin-28B CC genotype predict mortality in HIV and hepatitis C-coinfected individuals

    DEFF Research Database (Denmark)

    Clausen Nygaard, Louise; Astvad, Karen; Ladelund, Steen;

    2012-01-01

    : We hypothesized that hepatitis C virus (HCV) load and genotype may influence all-cause mortality in HIV-HCV-coinfected individuals.......: We hypothesized that hepatitis C virus (HCV) load and genotype may influence all-cause mortality in HIV-HCV-coinfected individuals....

  2. Reduction of viral load in whitefly (Bemisia tabaci Gen.) feeding on RNAi-mediated bean golden mosaic virus resistant transgenic bean plants.

    Science.gov (United States)

    de Paula, Nayhanne T; de Faria, Josias C; Aragão, Francisco J L

    2015-12-02

    The RNAi concept was explored to silence the rep gene from the bean golden mosaic virus (BGMV) and a genetically modified (GM) bean immune to the virus was previously generated. We investigated if BGMV-viruliferous whiteflies would reduce viral amount after feeding on GM plants. BGMV DNA amount was significantly reduced in whiteflies feeding in GM-plants (compared with insects feeding on non-GM plants) for a period of 4 and 8 days in 52% and 84% respectively.

  3. Viral arthritis

    Science.gov (United States)

    Infectious arthritis - viral ... Arthritis may be a symptom of many virus-related illnesses. It usually disappears on its own without ... the rubella vaccine, only a few people develop arthritis. No risk factors are known.

  4. Leukotriene B4 induces release of antimicrobial peptides in lungs of virally infected mice.

    Science.gov (United States)

    Gaudreault, Eric; Gosselin, Jean

    2008-05-01

    Leukotriene B(4) (LTB(4)) is a lipid mediator of inflammation that was recently shown to exert antiviral activities. In this study, we demonstrate that the release of antimicrobial proteins by neutrophils contribute to an early host defense against influenza virus infection in vitro as well as in vivo. Daily i.v. treatments with LTB(4) lead to a significant decrease in lung viral loads at day 5 postinfection in mice infected with influenza A virus compared with the placebo-treated group. This reduction in viral load was not present in mice deficient in the high-affinity LTB(4) receptor. Viral clearance in lungs was associated with up-regulated presence of antimicrobial peptides such as beta-defensin-3, members of the mouse eosinophil-related RNase family, and the mouse cathelicidin-related antimicrobial peptide. Our results also indicate that neutrophils are important in the antiviral effect of LTB(4). Viral loads in neutrophil-depleted mice were not diminished by LTB(4) administration, and a substantial reduction in the presence of murine cathelicidin-related antimicrobial peptide and the murine eosinophil-related RNase family in lung tissue was observed. Moreover, in vitro treatment of human neutrophil cultures with LTB(4) led rapidly to the secretion of the human cathelicidin LL-37 and eosinophil-derived neurotoxin, known as antiviral peptides. Pretreatment of cell cultures with specific LTB(4) receptor antagonists clearly demonstrate the implication of the high-affinity LTB(4) receptor in the LTB(4)-mediated activity. Together, these results demonstrate the importance of neutrophils and the secretion of antimicrobial peptides during the early immune response mediated by LTB(4) against a viral pathogen.

  5. Characterizing clearance of helper adenovirus by a clinical rAAV1 manufacturing process.

    Science.gov (United States)

    Thorne, Barbara A; Quigley, Paulene; Nichols, Gina; Moore, Christine; Pastor, Eric; Price, David; Ament, Jon W; Takeya, Ryan K; Peluso, Richard W

    2008-01-01

    Recombinant adeno-associated viral vectors (rAAV) are being developed as gene therapy delivery vehicles and as genetic vaccines, and some of the most scaleable manufacturing methods for rAAV use live adenovirus to induce production. One aspect of establishing safety of rAAV products is therefore demonstrating adequate and reliable clearance of this helper virus by the vector purification process. The ICH Q5A regulatory guidance on viral safety provides recommendations for process design and characterization of viral clearance for recombinant proteins, and these principles were adapted to a rAAV serotype 1 purification process for clinical vectors. Specific objectives were to achieve overall adenovirus clearance factors significantly greater than input levels by using orthogonal separation and inactivation methods, and to segregate adenovirus from downstream operations by positioning a robust clearance step early in the process. Analytical tools for process development and characterization addressed problematic in-process samples, and a viral clearance validation study was performed using adenovirus and two non-specific model viruses. Overall clearance factors determined were >23 LRV for adenovirus, 11 LRV for BVDV, and >23 LRV for AMuLV.

  6. Retrospective Evaluation of Low-pH Viral Inactivation and Viral Filtration Data from a Multiple Company Collaboration.

    Science.gov (United States)

    Mattila, John; Clark, Mike; Liu, Shengjiang; Pieracci, John; Gervais, Thomas R; Wilson, Eileen; Galperina, Olga; Li, Xinfang; Roush, David; Zoeller, Konstantin; Brough, Helene; Simpson-Platre, Christelle

    2016-01-01

    Considerable resources are spent within the biopharmaceutical industry to perform viral clearance studies, which are conducted for widely used unit operations that are known to have robust and effective retrovirus clearance capability. The collaborative analysis from the members of the BioPhorum Development Group Viral Clearance Working Team considers two common virus reduction steps in biopharmaceutical processes: low-pH viral inactivation and viral filtration. Analysis included eight parameters for viral inactivation and nine for viral filtration. The extensive data set presented in this paper provides the industry with a reference point for establishing robust processes in addition to other protocols available in the literature (e.g., ASTM Std. E2888-12 for low-pH inactivation). In addition, it identifies points of weakness in the existing data set and instructs the design and interpretation of future studies. Included is an abundance of data that would have been difficult to generate individually but collectively will help support modular viral clearance claims.

  7. Site clearance working group

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1997-03-01

    The Gulf of Mexico and Louisiana continue to be areas with a high level of facility removal, and the pace of removal is projected to increase. Regulations were promulgated for the Gulf of Mexico and Louisiana requiring that abandoned sites be cleared of debris that could interfere with fishing and shrimping activities. The site clearance regulations also required verification that the sites were clear. Additionally, government programs were established to compensate fishermen for losses associated with snagging their equipment on oil and gas related objects that remained on the water bottoms in areas other than active producing sites and sites that had been verified as clear of obstructions and snags. The oil and gas industry funds the compensation programs. This paper reviews the regulations and evolving operating practices in the Gulf of Mexico and Louisiana where site clearance and fisherman`s gear compensation regulations have been in place for a number of years. Although regulations and guidelines may be in place elsewhere in the world, this paper focuses on the Gulf of Mexico and Louisiana. Workshop participants are encouraged to bring up international issues during the course of the workshop. Additionally, this paper raises questions and focuses on issues that are of concern to the various Gulf of Mexico and Louisiana water surface and water bottom stakeholders. This paper does not have answers to the questions or issues. During the workshop participants will debate the questions and issues in an attempt to develop consensus opinions and/or make suggestions that can be provided to the appropriate organizations, both private and government, for possible future research or policy adjustments. Site clearance and facility removal are different activities. Facility removal deals with removal of the structures used to produce oil and gas including platforms, wells, casing, piles, pipelines, well protection structures, etc.

  8. Viral quasispecies.

    Science.gov (United States)

    Andino, Raul; Domingo, Esteban

    2015-05-01

    New generation sequencing is greatly expanding the capacity to examine the composition of mutant spectra of viral quasispecies in infected cells and host organisms. Here we review recent progress in the understanding of quasispecies dynamics, notably the occurrence of intra-mutant spectrum interactions, and implications of fitness landscapes for virus adaptation and de-adaptation. Complementation or interference can be established among components of the same mutant spectrum, dependent on the mutational status of the ensemble. Replicative fitness relates to an optimal mutant spectrum that provides the molecular basis for phenotypic flexibility, with implications for antiviral therapy. The biological impact of viral fitness renders particularly relevant the capacity of new generation sequencing to establish viral fitness landscapes. Progress with experimental model systems is becoming an important asset to understand virus behavior in the more complex environments faced during natural infections.

  9. The compliance contact model of cylindrical joints with clearances

    Institute of Scientific and Technical Information of China (English)

    Caishan Liu; Ke Zhang; Lei Yang; Keren Wang

    2005-01-01

    This paper is concerned with the determination of the normal force-displacement (NFD) relation for the contact problem of cylindrical joints with clearance. A simple formulation for this contact problem is developed by modeling the pin as a rigid wedge and the elastic plate as a simple Winkler elastic foundation. The numerical results show that the normal displacement relation based on Hertz theory is only valid for the case of large clearance with a small normal load, and the NFD relation based on Persson theory is only effective in the case of very small clearance. The proposed approximate model in this paper gives better results than Hertz theory and Persson theory in a large range of clearances as seen from the comparison with the results of FEM.

  10. Lithium clearance method and the renal response to low-dose dopamine in man

    DEFF Research Database (Denmark)

    Olsen, N V; Olsen, M H; Fogh-Andersen, N

    1993-01-01

    .00 hours on three different occasions. After an overnight fast, the subjects were water-loaded and clearance studies were started at 09.00 hours with a 1h baseline period and three 1h periods during dopamine infusion. 2. Baseline sodium clearance with placebo was 0.65 +/- 0.35 ml/min, but with lithium......, increase baseline values of sodium clearance and effective renal plasma flow.(ABSTRACT TRUNCATED AT 250 WORDS)...

  11. Association between risk factors, basal viral load, virus genotype and the degree of liver fibrosis with the response to the therapy in patients with chronic hepatitis C virus infection

    Directory of Open Access Journals (Sweden)

    Vuković Vuk R.

    2015-01-01

    Full Text Available Background/Aim. Hepatitis C is an important sociomedical problem worldwide due to frequent progression to chronic disease, occurrence of liver cirrhosis and hepatocellular carcinoma. Standard pegylated interferon alfa 2a plus ribavirin therapy results in resolution of infection only in 50% of patients. The aim of this study was to determine the association of various factors with response to the therapy in patients with chronic hepatitis C virus (HCV infection. Age and sex of patients, inoculation risk factors, histopathological changes in the liver, viral load and HCV genotype were analyzed. Methods. The study included a group of 121 patients with chronic HCV infection. The treatment was carried out 24 weeks for virus genotype 2 and 3, and 48 weeks for genotype 1 and 4. The degree of histopathological changes in the liver was determined by hematoxylin and eosin staining, whereas polimerase chain reaction was used for HCV genotyping. Results. In the group of non-responding patients genotype 1 was represented with 100%, while in the other groups, although predominantly present, its percentage was lower. Unresponsiveness to therapy and relapse of disease were associated with higher viral load and advanced fibrosis. Intravenous use of psychoactive substances, as a risk factor, was present in a high percentage in the group of patients with sustained response, while blood transfusion and dialysis were leading risk factors in the group of relapse responders and non-responders. Conclusion. The results of our study showed that the treatment outcome of chronic HCV infection was associated with baseline HCV ribonucleic acid, HCV genotype, route of infection and the degree of histopathological changes in the liver. [Projekat Ministarstva nauke Republike Srbije, br. III41010

  12. Effect of methotrexate and anti-TNF on Epstein-Barr virus T-cell response and viral load in patients with rheumatoid arthritis or spondylarthropathies

    Science.gov (United States)

    Miceli-Richard, Corinne; Gestermann, Nicolas; Amiel, Corinne; Sellam, Jérémie; Ittah, Marc; Pavy, Stephan; Urrutia, Alejandra; Girauld, Isabelle; Carcelain, Guislaine; Venet, Alain; Mariette, Xavier

    2009-01-01

    Introduction There is a suspicion of increased risk of Epstein-Barr virus (EBV)-associated lymphoproliferations in patients with inflammatory arthritides receiving immunosuppressive drugs. We investigated the EBV load and EBV-specific T-cell response in patients treated with methotrexate (MTX) or anti-TNF therapy. Methods Data for patients with rheumatoid arthritis (RA) (n = 58) or spondylarthropathy (SpA) (n = 28) were analyzed at baseline in comparison with controls (n = 22) and after 3 months of MTX or anti-TNF therapy for EBV load and EBV-specific IFNγ-producing T cells in response to EBV latent-cycle and lytic-cycle peptides. Results The EBV load and the number of IFNγ-producing T-cells after peptide stimulation were not significantly different between groups at baseline (P = 0.61 and P = 0.89, respectively). The EBV load was not significantly modified by treatment, for RA with MTX (P = 0.74) or anti-TNF therapy (P = 0.94) or for SpA with anti-TNF therapy (P = 1.00). The number of EBV-specific T cells was not significantly modified by treatment, for RA with MTX (P = 0.58) or anti-TNF drugs (P = 0.19) or for SpA with anti-TNF therapy (P = 0.39). For all patients, the EBV load and EBV-specific T cells were significantly correlated (P = 0.017; R = 0.21). For most patients, short-term exposure (3 months) to MTX or anti-TNF did not alter the EBV load or EBV-specific T-cell response but two patients had discordant evolution. Conclusions These data are reassuring and suggest there is no short-term defect in EBV-immune surveillance in patients receiving MTX or anti-TNF drugs. However, in these patients, long term follow-up of EBV-specific T-cell response is necessary and the role of non-EBV-related mechanisms of lymphomagenesis is not excluded. PMID:19470150

  13. 32 CFR 154.48 - Issuing clearance.

    Science.gov (United States)

    2010-07-01

    ... 32 National Defense 1 2010-07-01 2010-07-01 false Issuing clearance. 154.48 Section 154.48... PERSONNEL SECURITY PROGRAM REGULATION Issuing Clearance and Granting Access § 154.48 Issuing clearance. (a... personnel security clearance in the DCII (see § 154.43). A record of the clearance issued shall also...

  14. 24 CFR 35.1340 - Clearance.

    Science.gov (United States)

    2010-04-01

    ... 24 Housing and Urban Development 1 2010-04-01 2010-04-01 false Clearance. 35.1340 Section 35.1340... Hazard Evaluation and Hazard Reduction Activities § 35.1340 Clearance. Clearance examinations required... provisions of this section. (a) Clearance following abatement. Clearance examinations performed...

  15. Effect of methotrexate and anti-TNF on Epstein-Barr virus T-cell response and viral load in patients with rheumatoid arthritis or spondylarthropathies

    OpenAIRE

    Miceli-Richard, Corinne; Gestermann, Nicolas; Amiel, Corinne; Sellam, Jérémie; Ittah, Marc; Pavy, Stephan; Urrutia, Alejandra; Girauld, Isabelle; Carcelain, Guislaine; Venet, Alain; Mariette, Xavier

    2009-01-01

    Introduction There is a suspicion of increased risk of Epstein-Barr virus (EBV)-associated lymphoproliferations in patients with inflammatory arthritides receiving immunosuppressive drugs. We investigated the EBV load and EBV-specific T-cell response in patients treated with methotrexate (MTX) or anti-TNF therapy. Methods Data for patients with rheumatoid arthritis (RA) (n = 58) or spondylarthropathy (SpA) (n = 28) were analyzed at baseline in comparison with controls (n = 22) and after 3 mon...

  16. Reforming Customs Clearance in Pakistan

    OpenAIRE

    Ahmad, Manzoor

    2010-01-01

    Simple, fast, transparent customs clearance procedures encourage trade-and the resulting tariffs and related taxes raise government revenue and stimulate economic development. After outsourcing failed to make customs more efficient or increase revenue, in 2002 Pakistan began pursuing a modern single window system for customs clearance. In 2005 the system was introduced at the port of Karac...

  17. Analysis of Epstein-Barr viral DNA load, EBV-LMP2 specific cytotoxic T-lymphocytes and levels of CD4+CD25+T cells in patients with nasopharyngeal carcinomas positive for IgA antibody to EBV viral capsid antigen

    Institute of Scientific and Technical Information of China (English)

    MO Wu-ning; TANG An-zhou; ZHOU Ling; HUANG Guang-wu; WANG Zhan; ZENG Yi

    2009-01-01

    Background Epstein-Barr virus (EBV) is a herpesvirus commonly associated with several malignant diseases including nasopharyngeal carcinoma (NPC), which is a common cancer in Southeastem Asia. Previous studies showed that plasma levels of EBV-DNA might be a sensitive and reliable biomarker for the diagnosis, staging and evaluating of therapy for NPC. There are a few analyses of the levels of EBV-latent membrane protein 2 (LMP2)-specific cytotoxic T-lymphocytes (CTLs) in patients with NPC. This study was conducted to investigate the levels of EBV-LMP2-specific CTLs, EBV-DNA load and the level of CD4+CD25+T cells in such patients.Methods From February 2006 to April 2006, 62 patients with NPC, 40 healthy virus carders positive for EBV viral capsid antigen (EBV-IgA-VCA) and 40 controls were enrolled in the study. We used a highly sensitive ELISPOT assay,real-time polymerase chain reaction (PCR) and flow cytometry to measure the EBV-LMP2-specific CTL response, the EBV DNA load and the level of CD4+CD25+T cells, respectively.Results The EBV-LMP2-specific CTL responses of the samples from the control, healthy virus carders and patients with NPC were significantly different from the LMP2 epitopes, with the control and healthy virus carder samples displaying a stronger response in three cases. There were significant differences in EBV DNA load in serum between NPC and the healthy groups; patients with NPC at stages Ⅲ or Ⅳ had significantly higher viral loads compared with those at stages Ⅰ or Ⅱ. A significantly higher percentage of CD4+CD25+ T lymphocytes were detected in the patients, compared with healthy virus carriers and healthy controls. Moreover, patients with advanced stages of NPC (Ⅲ and Ⅲ) had significantly higher percentages than the patients with early stages (Ⅰ and Ⅱ).Conclusions Patients with NPC are frequently unable to establish or maintain sufficient immunosurveillance to control proliferating B cells harboring EBV and to destroy the tumor

  18. High Viral Loads of Epstein-Barr Virus DNA in Peripheral Blood of Patients with Chronic Lymphocytic Leukemia Associated with Unfavorable Prognosis.

    Science.gov (United States)

    Grywalska, Ewelina; Roliński, Jacek; Pasiarski, Marcin; Korona-Glowniak, Izabela; Maj, Maciej; Surdacka, Agata; Grafka, Agnieszka; Stelmach-Gołdyś, Agnieszka; Zgurski, Michał; Góźdź, Stanisław; Malm, Anna; Grabarczyk, Piotr; Starosławska, Elżbieta

    2015-01-01

    Epstein-Barr virus (EBV) is a ubiquitous γ-herpesvirus that infects more than 90% of the world population. The potential involvement of EBV in the clinical course of chronic lymphocytic leukemia (CLL) remains unexplained. The aim of this study was to determine whether EBV-DNA load in the peripheral blood mononuclear cells (PBMCs) of CLL patients may influence heterogeneity in the course of the disease. The study included peripheral blood samples from 115 previously untreated patients with CLL (54 women and 61 men) and 40 healthy controls (16 women and 24 men). We analyzed the association between the EBV-DNA load in PBMCs and the stage of the disease, adverse prognostic factors, and clinical outcome. Detectable numbers of EBV-DNA copies in PBMCs were found in 62 out of 115 CLL patients (53.91%). The EBV-DNA copy number/μg DNA was significantly higher in patients who required early implementation of treatment, presented with lymphocyte count doubling time DNA copy number/μg DNA showed significant positive correlation with the concentrations of lactate dehydrogenase (LDH) and beta-2-microglobulin. We have shown that in CLL patients, higher EBV-DNA copy number predicted shorter survival and shorter time to disease progression, and it was associated with other established unfavorable prognostic factors. This suggests that EBV may negatively affect the outcome of CLL.

  19. Lithium clearance method and the renal response to low-dose dopamine in man

    DEFF Research Database (Denmark)

    Olsen, Niels Vidiendal; Olsen, M H; Fogh-Andersen, N

    1993-01-01

    .00 hours on three different occasions. After an overnight fast, the subjects were water-loaded and clearance studies were started at 09.00 hours with a 1h baseline period and three 1h periods during dopamine infusion. 2. Baseline sodium clearance with placebo was 0.65 +/- 0.35 ml/min, but with lithium.......05) and 10% (P sodium clearance were significantly diminished after 450mg (P ... values of sodium clearance and effective renal plasma flow.(ABSTRACT TRUNCATED AT 250 WORDS)...

  20. 30 CFR 18.24 - Electrical clearances.

    Science.gov (United States)

    2010-07-01

    ... Requirements § 18.24 Electrical clearances. Minimum clearances between uninsulated electrical conductor surfaces, or between uninsulated conductor surfaces and grounded metal surfaces, within the enclosure...

  1. Dynamic changes of dengue viral loads and IgM antibody and their relationships with disease severity%登革病毒载量和IgM抗体水平与疾病严重程度的关系

    Institute of Scientific and Technical Information of China (English)

    赵令斋; 高秀洁; 庾蕾; 洪文昕; 邱爽; 王建; 张复春

    2016-01-01

    Objective To investigate the dynamic changes of dengue viral loads and IgM antibody in patients with dengue fever ( DF) and to analyze their relationships with disease severity. Methods A to-tal of 1 508 serum samples were collected from 1 140 hospitalized patients including 1 050 mild cases and 90 severe cases within 10 days after the onset of DF in Guangzhou in 2014. The viral loads were determined by using fluorescence quantitative RT-PCR. ELISA was performed to measure the dengue virus ( DENV)-spe-cific IgM antibody. Results In general, the DENV viral loads in patients declined gradually from 108 copies/ml on day 1 to 103 copies/ml on day 10 after the onset of DF. The viral loads in severe cases were significantly higher than those in mild cases on days 5 to 7 (P<0. 05). The positive rates of DENV RNA in serum samples also decreased with the disease progression from 100% on day 1 to 40% on day 10. Com-pared with the mild cases, the patients with severe DF showed higher positive rates of DENV RNA on day 6 and day 8 (P<0. 05). The DENV-specific IgM antibody could be detected on day 2 and the secretion of IgM antibody increased gradually with the disease progression. The levels of IgM antibody in mild cases were sig-nificantly higher than those in severe cases (P<0. 001). The positive rates of IgM antibody in patients in-creased form 8% on day 2 to 95% on day 6. Higher positive rates of IgM antibody were detected in mild ca-ses on days 5 and 6 as compared with those in patients with severe DF (P<0. 05). Conclusion High viral load and low level of IgM antibody during the fastigium of DF were closely associated with the disease severity.%目的:探讨登革热( dengue fever ,DF)患者病毒载量和特异性IgM抗体在疾病过程中的动态变化规律及其与疾病严重程度的相关性。方法收集1140例DF患者(其中轻症1050例,重症90例)发病第1~10天的血清1508份,用荧光定量PCR法检测病毒载量,ELISA法检

  2. High Viral Loads of Epstein-Barr Virus DNA in Peripheral Blood of Patients with Chronic Lymphocytic Leukemia Associated with Unfavorable Prognosis.

    Directory of Open Access Journals (Sweden)

    Ewelina Grywalska

    Full Text Available Epstein-Barr virus (EBV is a ubiquitous γ-herpesvirus that infects more than 90% of the world population. The potential involvement of EBV in the clinical course of chronic lymphocytic leukemia (CLL remains unexplained. The aim of this study was to determine whether EBV-DNA load in the peripheral blood mononuclear cells (PBMCs of CLL patients may influence heterogeneity in the course of the disease. The study included peripheral blood samples from 115 previously untreated patients with CLL (54 women and 61 men and 40 healthy controls (16 women and 24 men. We analyzed the association between the EBV-DNA load in PBMCs and the stage of the disease, adverse prognostic factors, and clinical outcome. Detectable numbers of EBV-DNA copies in PBMCs were found in 62 out of 115 CLL patients (53.91%. The EBV-DNA copy number/μg DNA was significantly higher in patients who required early implementation of treatment, presented with lymphocyte count doubling time <12 months, displayed CD38-positive or ZAP-70-positive phenotype, and with the del(11q22.3 cytogenetic abnormality. Furthermore, the EBV-DNA copy number/μg DNA showed significant positive correlation with the concentrations of lactate dehydrogenase (LDH and beta-2-microglobulin. We have shown that in CLL patients, higher EBV-DNA copy number predicted shorter survival and shorter time to disease progression, and it was associated with other established unfavorable prognostic factors. This suggests that EBV may negatively affect the outcome of CLL.

  3. P-glycoprotein (ABCB1) activity decreases raltegravir disposition in primary CD4+P-gphigh cells and correlates with HIV-1 viral load

    Science.gov (United States)

    Minuesa, Gerard; Arimany-Nardi, Cristina; Erkizia, Itziar; Cedeño, Samandhy; Moltó, José; Clotet, Bonaventura; Pastor-Anglada, Marçal; Martinez-Picado, Javier

    2016-01-01

    Objectives To evaluate the role of P-glycoprotein (P-gp) and multidrug-resistant-protein 1 (MRP1) on raltegravir intracellular drug disposition in CD4+ T cells, investigate the effect of HIV-1 infection on P-gp expression and correlate HIV-1 viraemia with P-gp activity in primary CD4+ T cell subsets. Methods The cellular accumulation ratio of [3H]raltegravir was quantified in CD4+ T cell lines overexpressing either P-gp (CEM-P-gp) or MRP1 (CEM-MRP1) and in primary CD3+CD4+ T cells with high (P-gphigh) and low P-gp activity (P-gplow); inhibition of efflux transporters was confirmed by the intracellular retention of calcein-AM. The correlation of P-gp activity with HIV-1 viraemia was assessed in naive and memory T cell subsets from 21 HIV-1-infected treatment-naive subjects. Results [3H]Raltegravir cellular accumulation ratio decreased in CEM-P-gp cells (P < 0.0001). XR9051 (a P-gp inhibitor) and HIV-1 PIs reversed this phenomenon. Primary CD4+P-gphigh cells accumulated less raltegravir (38.4% ± 9.6%) than P-gplow cells, whereas XR9051 also reversed this effect. In vitro HIV-1 infection of PBMCs and stimulation of CD4+ T cells increased P-gp mRNA and P-gp activity, respectively, while primary CD4+P-gphigh T cells sustained a higher HIV-1 replication than P-gplow cells. A significant correlation between HIV-1 viraemia and P-gp activity was found in different CD4+ T cell subsets, particularly memory CD4+ T cells (r = 0.792, P < 0.0001). Conclusions Raltegravir is a substrate of P-gp in CD4+ T cells. Primary CD4+P-gphigh T cells eliminate intracellular raltegravir more readily than P-gplow cells and HIV-1 viraemia correlates with P-gp overall activity. Specific CD4+P-gphigh T cell subsets could facilitate the persistence of viral replication in vivo and ultimately promote the appearance of drug resistance. PMID:27334660

  4. 核酸检测中HIV病毒载量对内质控扩增的影响%Effects of HIV viral load on internal control amplification by using NAT technique

    Institute of Scientific and Technical Information of China (English)

    余谨; 毕昊; 陆华新; 王先广; 赵磊; 沈钢

    2012-01-01

    目的 评估酶联免疫法的窗口期HIV血样.方法 将酶联免疫法阴性标本采用六混样用2种试剂进行平行核酸检测,在检测出阳性标本后,亦用2种试剂对其拆分进行单管核酸检测.结果 10个月内共筛查16769例酶联免疫阴性标本中,核酸检测出1例HIV阳性标本,罗氏一代试剂由于该标本病毒载量浓度过高体现出抑制作用,罗氏二代试剂未显示出抑制作用.结论 目前现行开展的检测技术仍有安全隐患,为进一步保证临床用血的安全,开展核酸检测可以提高临床用血质量,为临床安全用血提供强有力的保障.%Objective To determine the prevalence of viral infections (HBV.HCV and HIV) in serological window period in blood donors screened with nucleic acid testing (NAT) . Methods All blood donors were tested with serological tests( Ag-HBVs,Anti-HCV and Anti-HIV)and molecular testing with NAT by PP6 and rPPl for HBV.HCV and HIV. The window period was defined with the positive NAT and negative serological test. Results During ten months, we evaluated 16 769 blood donors. One subject was identified with HIV in serological window period. HIV viral load has the effect on internal control amplification by using NAT technique. Conclusion Unsafe blood in the performance of viral infections due to HIV in serological window period in donors by using NAT technique.

  5. Correlation analysis between plasma and colostrum viral load in hepatitis B virus carrier puerperae%乙肝病毒携带产妇血浆与初乳中病毒含量的相关性研究

    Institute of Scientific and Technical Information of China (English)

    朱召芹; 张晓红; 张丽岩; 蒋佩如; 胡芸文; 韩志敏

    2012-01-01

    目的 探讨乙肝病毒携带产妇血浆及初乳中病毒含量的差异性及其临床意义.方法 选取20例乙肝病毒携带产妇作为实验组,21例乙肝表面抗原阴性的健康产妇作为对照组,采用RT-PCR法检测实验组及对照组血浆及初乳中HBV DNA病毒含量.结果 对照组产妇的初乳和血液中HBV DNA均检测阴性.实验组产妇初乳中HBV DNA含量与血浆中HBV DNA含量有一定相关性,Ct值和病毒载量相关系数r分别为0.7731和0.8053,P值均小于0.0001.实验组血浆中HBVDNA含量明显高于初乳中HBV DNA含量10~1000倍(P<0.0001).当血浆HBV DNA国际单位(IU)的Log值下降到4.7以下时,75%的乙肝病毒携带产妇初乳中病毒DNA是低于检测限.结论 血浆和乳汁中HBV DNA载量较低的乙肝病毒携带产妇可结合其它临床检测指标部分考虑采取母乳喂养.%Objective To investigate the correlation between plasma and colostrum viral load in carrier puerperae and evaluate its clinical significance.Methods 20 cases of hepatitis B virus carrier puerperae were enrolled as the experimental group,21 cases of hepatitis B surface antigen-negative healthy puerperae were selected as a control group.HBV DNA was detected by RT-PCR.Results HBV DNA was below the lowest detection limit both in colostrum and plasma in control group.In HBV carrier group,a statistically significant direct correlation was observed(r=0.8053,P<0.0001)between colostrum and plasma HBV viral load.The concentration of HBV DNA in plasma was 10 to 1000 fold(P<0.0001)higher than that in colostrum.When plasma HBV DNA load in the Log value dropped to below 4.7 IU,colostrum viral DNA of 75% hepatitis B virus carrier puerperae was below the detection limitation.Conclusion The puerperae with low levels of HBV DNA in colostrum and plasma could be considered to applied breastfeeding.

  6. Lithium clearance in chronic nephropathy

    DEFF Research Database (Denmark)

    Kamper, A L; Holstein-Rathlou, N H; Leyssac, P P

    1989-01-01

    1. Lithium clearance measurements were made in 72 patients with chronic nephropathy of different aetiology and moderate to severely reduced renal function. 2. Lithium clearance was strictly correlated with glomerular filtration rate, and there was no suggestion of distal tubular reabsorption...... clearance data were independent of whether renal disease was of primarily glomerular or tubular origin and, further, were not influenced by long-term conventional antihypertensive treatment. 6. It is concluded that, even with a reduced kidney function, the data are compatible with the suggestion...... that lithium clearance may be a measure of the delivery of sodium and water from the renal proximal tubule. With this assumption it was found that adjustment of the sodium excretion in chronic nephropathy initially takes place in the distal parts of the nephron (loop of Henle, distal tubule and collecting duct...

  7. Carga viral do papilomavirus humano na predição da gravidade de lesões cervicais em mulheres com atipias celulares na colpocitologia oncológica Viral load of human papillomavirus as a predictor of the severity of cervical lesions in women with atypical cells at pap smear

    Directory of Open Access Journals (Sweden)

    Luis Otávio Zanatta Sarian

    2003-06-01

    Full Text Available OBJETIVO: avaliar o desempenho da carga viral do HPV por captura de híbridos II (CHII na predição da gravidade das lesões cervicais. MÉTODOS: foram incluídas 309 mulheres admitidas por resultado anormal da colpocitologia oncológica (CO entre agosto de 200 e novembro de 2002. Todas foram submetidas a avaliação histológica, sendo que a presença de neoplasia intra-epitelial cervical (NIC grau 2 ou mais (NIC 3, carcinoma invasor foi considerada doença grave. A CHII foi realizada para tipos de HPV de alto risco oncogênico e a carga viral medida em unidades relativas de luz (URL. O desempenho da CHII foi avaliado por curva receiver operating characteristics (ROC. RESULTADOS: na avaliação histológica, 140 (45,3% mulheres apresentavam cervicite ou NIC 1 e 199 (54,7%, NIC 2/3, adenocarcinoma in situ ou câncer invasor. O melhor ponto de corte da CHII para a detecção de doença grave foi 35 URL, com sensibilidade de 69% e especificidade de 70%. O valor preditivo positivo das alterações compatíveis com lesão de alto grau na CO associado a CHII de 35 URL (unidades relativas de luz foi de 88,2% para a detecção de NIC 2 ou mais. Já 95,7% das mulheres com lesões de baixo grau na CO e CHII menor que 1 URL não apresentaram lesões histológicas graves. CONCLUSÃO: o melhor desempenho da CHII no diagnóstico de NIC 2 ou lesão mais grave foi encontrado com 35 URL. A associação da CO com a CHII em diferentes cargas virais mostrou valores preditivos positivos e negativos muito altos.PURPOSE: to assess the performance of hybrid capture II (HCII HPV viral load in predicting the grade of cervical lesions. METHODS: between August 2000 to November 2002, 309 women admitted due to an abnormal Pap smear result were recruited. Histological disease confirmation was done in all women and cervical intraepithelial neoplasia (CIN grade 2 or above was considered as severe disease. HCII was done for high-risk HPV types and viral load was estimated in

  8. CXCR5(+) CD8(+) T Cells Indirectly Offer B Cell Help and Are Inversely Correlated with Viral Load in Chronic Hepatitis B Infection.

    Science.gov (United States)

    Jiang, Hang; Li, Linhai; Han, Jiang; Sun, Zhiwei; Rong, Yihui; Jin, Yun

    2017-04-01

    Treatment options for chronic hepatitis B (CHB) infection are extremely limited. CXCR5(+) CD8(+) T cell is a novel cell subtype and could possess strong cytotoxic properties in HIV infection. In this study, we investigated the role of CXCR5(+) CD8(+) T cells in CHB patients. Compared to healthy individuals, both CHB patients and hepatitis B virus (HBV)-infected hepatocellular carcinoma patients presented significant upregulation of CXCR5(+) CD8(+) T cells in peripheral blood, in which CXCR5(+) CD8(+) T cells were negatively correlated with the frequency of CXCR5(+) CD4(+) T cells in CHB patients. After PMA+ionomycin stimulation, CXCR5(+) CD8(+) T cells from CHB patients presented significantly higher transcription level of interferon gamma (IFN-γ), interleukin 10 (IL-10), and IL-21, as well as higher IL-10 and IL-21 protein secretion, than CXCR5(-) CD8(+) T cells. Unlike CXCR5(+) CD4(+) T cells, when incubated with naive CD19(+)CD27(-) B cells, CXCR5(+) CD8(+) T cells alone did not upregulate IgM, IgG, and IgA secretion. However, addition of CXCR5(+) CD8(+) T cells in B cell-CXCR5(+) CD4(+) T cell coculture significantly increased the levels of secreted IgG and IgA, demonstrating that CXCR5(+) CD8(+) T cell could indirectly offer B cell help. Furthermore, high frequencies of CXCR5(+) CD8(+) T cells tended to associate with low HBV DNA load, and the frequency of CXCR5(+) CD8(+) T cells was negatively correlated with alanine aminotransferase (ALT) level. Together, these results suggested that CXCR5(+) CD8(+) T cells were involved in the antiviral immune responses in CHB and could potentially serve as a therapeutic candidate.

  9. Dietary aluminosilicate supplement enhances immune activity in mice and reinforces clearance of porcine circovirus type 2 in experimentally infected pigs.

    Science.gov (United States)

    Jung, Bock-Gie; Toan, Nguyen Tat; Cho, Sun-Ju; Ko, Jae-hyung; Jung, Yeon-Kwon; Lee, Bong-Joo

    2010-07-14

    Aluminosilicate is the major component of clay minerals such as zeolite, bentonite and clinoptilolite. The minerals possess a number of beneficial activities, especially in regulating the immune system. The aims of the present study were to evaluate immune enhancing effects of dietary aluminosilicate supplement (DAS) in mice, and to demonstrate clearance effects of DAS against porcine circovirus type 2 (PCV2) in experimentally infected pigs as an initial step towards the development of an antibiotic substitute for use in pigs. Relative messenger RNA expression levels of interferon-gamma, interleukin-4 and tumor necrosis factor-alpha, phagocytic activities of polymorphonuclear leucocytes, serum antibody production level and spleen B cell ratio were significantly increased in the DAS groups of mice compared with the control group (each feeding group had three replications with 5 mice each). The results indicated that general immune activity including cellular and humoral immunity could be enhanced by DAS in mice. In experimentally PCV2-infected pigs, the load of viral genome in nasal swab, serum and lung of the DAS group of pigs was significantly decreased compared with the control group at 28 days post-infection (each group three pigs). Corresponding histopathological analyses demonstrated that pigs in the DAS group displayed mild and less severe abnormal changes compared with the control group, indicating that DAS reinforces clearance of PCV2 in experimentally infected pigs. This may relate to general immune enhancing effects of DAS in mice. Therefore DAS will help the health of animal, especially in swine.

  10. 33 CFR 117.47 - Clearance gauges.

    Science.gov (United States)

    2010-07-01

    ... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Clearance gauges. 117.47 Section... OPERATION REGULATIONS General Requirements § 117.47 Clearance gauges. (a) Clearance gauges are required for... specify otherwise for particular drawbridges, clearance gauges shall be designed, installed,...

  11. 30 CFR 57.11010 - Stairstep clearance.

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Stairstep clearance. 57.11010 Section 57.11010... Escapeways Travelways-Surface and Underground § 57.11010 Stairstep clearance. Vertical clearance above stair... to indicate an impaired clearance....

  12. 30 CFR 56.11008 - Restricted clearance.

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Restricted clearance. 56.11008 Section 56.11008 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE... Restricted clearance. Where restricted clearance creates a hazard to persons, the restricted clearance...

  13. 30 CFR 56.11010 - Stairstep clearance.

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Stairstep clearance. 56.11010 Section 56.11010... Stairstep clearance. Vertical clearance above stair steps shall be a minimum of seven feet, or suitable warning signs or similar devices shall be provided to indicate an impaired clearance....

  14. 30 CFR 57.11008 - Restricted clearance.

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Restricted clearance. 57.11008 Section 57.11008... Escapeways Travelways-Surface and Underground § 57.11008 Restricted clearance. Where restricted clearance creates a hazard to persons, the restricted clearance shall be conspicuously marked....

  15. 14 CFR 25.925 - Propeller clearance.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Propeller clearance. 25.925 Section 25.925... STANDARDS: TRANSPORT CATEGORY AIRPLANES Powerplant General § 25.925 Propeller clearance. Unless smaller clearances are substantiated, propeller clearances with the airplane at maximum weight, with the most...

  16. 32 CFR 154.16 - Security clearance.

    Science.gov (United States)

    2010-07-01

    ... 32 National Defense 1 2010-07-01 2010-07-01 false Security clearance. 154.16 Section 154.16... clearance. (a) General. (1) The authorities designated in paragraph A, Appendix E are the only authorities authorized to grant, deny or revoke DoD personnel security clearances. The granting of such clearances...

  17. 28 CFR 524.74 - Activities clearance.

    Science.gov (United States)

    2010-07-01

    ... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Activities clearance. 524.74 Section 524... clearance. (a) Except as provided for in paragraph (b) of this section, the Warden is the clearance... Security cases. Central Office Inmate Monitoring Section staff shall be the clearance authority on...

  18. Factors Associated with Spontaneous Clearance of Hepatitis C Virus in Chinese Population

    Directory of Open Access Journals (Sweden)

    Fei Kong

    2014-01-01

    Full Text Available Hepatitis C virus (HCV infections spontaneously clear in approximately 15–45% of infected individuals. Factors which influence spontaneous HCV clearance remain to be identified. The purpose of the present study was to identify variables associated with spontaneous HCV clearance in a referred population of Chinese patients. The prevalence of host, viral, and environmental factors known to influence the outcome of HCV infections was compared in 92 HCV spontaneous clearance subjects and 318 HCV persistent infection subjects. Univariate and multivariate analyses were performed to identify those factors associated with spontaneous HCV clearance. In univariate analysis, female gender, a history of icteric hepatitis, serologic evidence of concurrent HBV infection, and rs12979860 CC genotype were positively associated with spontaneous HCV clearance, while alcohol consumption was negatively associated with clearance. In multivariate analysis, female gender, a history of icteric hepatitis, concurrent HBV infection, and rs12979860 CC genotype remained independent variables associated with spontaneous HCV clearance. Spontaneous HCV clearance is more likely to occur in females, subjects with a history of icteric hepatitis, HBV coinfections, and those with the rs12979860 CC genotype.

  19. Exaggerated natriuresis and lithium clearance in spontaneously hypertensive rats

    DEFF Research Database (Denmark)

    Holstein-Rathlou, N H; Kanters, J K; Leyssac, P P

    1988-01-01

    Since hypertension is associated with changes in the handling of various cations (including sodium and lithium) across the cell membrane, the present study investigated the validity of the lithium clearance method in hypertension by comparing two measures of proximal reabsorption. Thus, fractional...... lithium excretion and transit time (TT)-occlusion time (OT; e-TT/T) were determined successively in the same spontaneously hypertensive rat (SHR, Okamoto strain). The rats were examined both before and after an acute saline load. The results show that the lithium clearance method can be used...... for the determination of proximal reabsorption in SHR. Utilizing the lithium clearance method, the changes in renal sodium handling underlying the exaggerated natriuresis were investigated in unanaesthetized catheterized rats. It was found that the exaggerated natriuresis was associated with an increased output from...

  20. The complex relationship between CD4 count, HIV viral load, trimethoprim-sulfamethoxazole prophylaxis, and skin-and-soft-tissue infection risk in patients with HIV: insights from a causal diagram and simulation study.

    Science.gov (United States)

    Hemmige, V; Lauderdale, D S; David, M Z

    2016-10-01

    Skin and soft tissue infection (SSTIs) due to Staphylococcus aureus, particularly community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA), are common in human immunodeficiency virus (HIV)-infected populations in the United States. Studies have differed as to the importance of epidemiological and immunological factors in this relationship, and have employed conflicting strategies for variable selection in multivariate analyses. Developments in causal inference methods in epidemiology have emerged in the last decade to clarify relationships between variables and identify appropriate variables to include in and exclude from multivariate analysis. In this paper, we develop a causal diagram to clarify the pathways linking CA-MRSA and HIV. We focus on the role played by trimethoprim-sulfamethoxazole (TMP-SMX) prophylaxis, prescribed to many severely immunocompromised HIV patients and potentially protective against SSTIs, which both mediates and moderates the relationship between immunological parameters and SSTI risk. We demonstrate, using simulated data, that statistical models may yield biased results if they do not account for how HIV viral load may also be a marker of adherence to TMP-SMX prophylaxis. We conclude with a proposed causal model that includes both the epidemiological as well as immunological factors that may explain the increased risk of initial and recurrent SSTI risk in HIV-infected populations.

  1. Lithium clearance in chronic nephropathy

    DEFF Research Database (Denmark)

    Kamper, A L; Holstein-Rathlou, N H; Leyssac, P P

    1989-01-01

    1. Lithium clearance measurements were made in 72 patients with chronic nephropathy of different aetiology and moderate to severely reduced renal function. 2. Lithium clearance was strictly correlated with glomerular filtration rate, and there was no suggestion of distal tubular reabsorption...... of lithium or influence of osmotic diuresis. 3. Fractional reabsorption of lithium was reduced in most patients with glomerular filtration rates below 25 ml/min. 4. Calculated fractional distal reabsorption of sodium was reduced in most patients with glomerular filtration rates below 50 ml/min. 5. Lithium...... that lithium clearance may be a measure of the delivery of sodium and water from the renal proximal tubule. With this assumption it was found that adjustment of the sodium excretion in chronic nephropathy initially takes place in the distal parts of the nephron (loop of Henle, distal tubule and collecting duct...

  2. Lactate clearance in cardiorespiratory emergency

    Directory of Open Access Journals (Sweden)

    Serena Greco

    2007-08-01

    Full Text Available Early goal directed therapy has been found to improve prognosis in septic patients, if the therapeutic goal is achieved within the first six hours. The aim of our study is to demonstrate that in patients with acute cardiorespiratory failure, rapid (within 2 hours lactate clearance can help define patients’ prognosis. 67 consecutive patients, admitted to our 16-bed Emergency Medicine ward for acute cardiorespiratory failure (age 75,9 ± 9,8 (APACHE II score 19,0 ± 4,1, were included in the study. Blood lactate concentration was read at admission and after 2, 6 and 24 hours. We evaluated mortality at seven days and the use of orotracheal intubation (patients with negative outcome vs. discharge or transfer to a non-emergency ward with subsequent discharge (patients with negative outcome. Lactate concentration at admission was 4,6 ± 2,5 mmol/l; lactate clearance (% at 2 hours was 40,4 ± 32,1 in patients with a positive outcome and –8,3 ± 5,0 in patients with a negative outcome (p < 0,05. Lactate clearance at 2 hours < 25% is correlated to a negative outcome with an 84,2% sensitivity and a 79,2% specificity. The positive predictive value was 61,5% and the negative predictive value was 92,2%. Systematic lactate clearance monitoring can be used in cases of acute cardiorespiratory insufficiency to identify patients with a high risk of negative outcome. In our study, low clearance at two hours was associated with an increase in mortality and/or the need for orotracheal intubation. Conversely, a clearance at two hours of > 25% in most cases confirms the therapeutic strategy undertaken. Serial evaluation of blood lactate concentration may therefore be useful in guiding treatment strategies.

  3. Numerical analysis of bump foil bearings without nominal radial clearance

    Institute of Scientific and Technical Information of China (English)

    LIU Zhan-sheng; XU Huai-jin; ZHANG Guang-hui

    2008-01-01

    Bump foil bearings without nominal radial clearance were analyzed. An air film thickness model and a bearing theoretical analytical model were developed accounting for air compressibility and foil deformation. To analyze hydrodynamic characteristics of bump foil beatings with different operating eccentricities, the air film thickness equation and Reynolds equation were coupled through pressure and solved by Newton-Raphson Method(NRM) and Finite Difference Method (FDM). The characteristics of an bump foil bearing model were dis-cussed including load carrying capacity, film thickness and pressure distributions. The results of simulation show that bump foil beating without nominal radial clearance can provide better stability and greater load capaci-ty. This numerical analytical method also reveals a good convergence in numerical calculation.

  4. Comparison of HPV detection technologies: Hybrid capture 2, PreTect HPV-Proofer and analysis of HPV DNA viral load in HPV16, HPV18 and HPV33 E6/E7 mRNA positive specimens.

    LENUS (Irish Health Repository)

    Keegan, Helen

    2012-02-01

    Human papillomavirus (HPV) testing using molecular methods in liquid based cytology (LBC) specimens may be useful as an adjunct to cervical screening by cytology. We compared the positivity rate of the commercially available HPV DNA method hybrid capture 2 (hc2) and the commercially available E6\\/E7 mRNA method PreTect HPV-Proofer in cytological specimens (n=299). LBC specimens collected (n=299) represented the following cervical cytological disease categories: Normal (n=60), borderline nuclear abnormalities (BNA) (n=34), CIN1 (n=121), CIN2 (n=60), CIN3 (n=24). Overall, 69% (205\\/299) of the cases were positive by hc2 and 38% (112\\/299) of the cases were positive by PreTect HPV-Proofer. Concordance rates between the two tests were highest in the high-grade cytology cases (CIN2: 67% and CIN3: 83%) and the normal cytology cases (88%) and lowest in the BNA and CIN1 categories (56% and 52%). HPV DNA viral load analyses were carried out on HPV16 (n=55), HPV18 (n=9) and HPV33 (n=13) samples that were positive by PreTect HPV-Proofer. The sensitivity and specificity of PreTect HPV-Proofer and the hc2 DNA test for the detection of high-grade cytology (i.e. CIN2+) were 71.4% and 75.8% vs 100% and 43.7%, respectively. The relatively low detection rate observed by PreTect HPV-Proofer in the whole range of cytological positive cases, combined with a relatively higher specificity and PPV, suggests that PreTect HPV-Proofer may be more useful than hc2 for triage and in predicting high-grade disease.

  5. Re-entry flight clearance

    NARCIS (Netherlands)

    Juliana, S.

    2006-01-01

    The objective of the research was to identify and evaluate promising mathematical techniques for re-entry flight clearance. To fulfil this objective, two mathematical methods were investigated and developed: μ analysis for linear models and interval analysis for both linear and non-linear model

  6. A randomized, controlled, molecular study of condylomata acuminata clearance during treatment with imiquimod.

    Science.gov (United States)

    Tyring, S K; Arany, I; Stanley, M A; Tomai, M A; Miller, R L; Smith, M H; McDermott, D J; Slade, H B

    1998-08-01

    Imiquimod, an immune response modifier, has been demonstrated to be safe and effective in the treatment of external genital and perianal warts caused by human papillomavirus (HPV). To identify the molecular mechanism(s) by which condylomata acuminata clear during topical treatment with imiquimod, wart skin biopsies were taken from patients before treatment, at treatment week 6, and at the end of treatment. Tissues were analyzed for HPV DNA and for mRNA of several cytokines and HPV gene products. Wart clearance was associated with evidence of tissue production of interferon-alpha, -beta, and -gamma and tumor necrosis factor-alpha. Regression of warts was strongly associated with a decrease in HPV DNA and in mRNA expression for both early and late viral proteins. Thus, topical imiquimod treatment of anogenital warts led to significant increases in local production of multiple interferon mRNAs and a significant reduction in virus load as measured by decreases in HPV DNA and mRNA for early HPV proteins.

  7. 49 CFR 192.325 - Underground clearance.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 3 2010-10-01 2010-10-01 false Underground clearance. 192.325 Section 192.325... Lines and Mains § 192.325 Underground clearance. (a) Each transmission line must be installed with at least 12 inches (305 millimeters) of clearance from any other underground structure not associated...

  8. Aerial Refueling Clearance Initiation Request

    Science.gov (United States)

    2016-07-14

    8. Material Tiiie 6. E-mail Address derek.feiwerda@uavy.mil Aerial Refueling Clearance Initiation Request 9. List all contributing organizations...and obtain Public Retease Authorization from the commnnd(s) contributing to this material. I have reviewed all the applicable security classification...AUTHOR(S) Hewitt, Keith; Graham, Jessica; Swiderek, Thomas; Kalt, Dexter; ARSAG Working Group 5 Participants 5d. PROJECT NUMBER N/A 5e. TASK NUMBER N

  9. A novel approach to achieving modular retrovirus clearance for a parvovirus filter.

    Science.gov (United States)

    Stuckey, Juliana; Strauss, Daniel; Venkiteshwaran, Adith; Gao, Jinxin; Luo, Wen; Quertinmont, Michelle; O'Donnell, Sean; Chen, Dayue

    2014-01-01

    Viral filtration is routinely incorporated into the downstream purification processes for the production of biologics produced in mammalian cell cultures (MCC) to remove potential viral contaminants. In recent years, the use of retentive filters designed for retaining parvovirus (~20 nm) has become an industry standard in a conscious effort to further improve product safety. Since retentive filters remove viruses primarily by the size exclusion mechanism, it is expected that filters designed for parvovirus removal can effectively clear larger viruses such as retroviruses (~100 nm). In an attempt to reduce the number of viral clearance studies, we have taken a novel approach to demonstrate the feasibility of claiming modular retrovirus clearance for Asahi Planova 20N filters. Porcine parvovirus (PPV) and xenotropic murine leukemia virus (XMuLV) were co-spiked into six different feedstreams and then subjected to laboratory scale Planova 20N filtration. Our results indicate that Planova 20N filters consistently retain retroviruses and no retrovirus has ever been detected in the filtrates even when significant PPV breakthrough is observed. Based on the data from multiple in-house viral validation studies and the results from the co-spiking experiments, we have successfully claimed a modular retrovirus clearance of greater than 6 log10 reduction factors (LRF) to support clinical trial applications in both USA and Europe.

  10. Principles underlying the epizootiology of viral hemorrhagic septicemia in Pacific herring and other fishes throughout the North Pacific Ocean

    Science.gov (United States)

    Hershberger, Paul K.; Garver, Kyle A.; Winton, James R.

    2016-01-01

    Although viral hemorrhagic septicemia virus (VHSV) typically occurs at low prevalence and intensity in natural populations of Pacific herring (Clupea pallasii) and other marine fishes in the Northeast Pacific Ocean, epizootics of the resulting disease (VHS) periodically occur, often in association with observed fish kills. Here we identify a list of principles, based on a combination of field studies, controlled laboratory experiments, and previously unpublished observations, that govern the epizootiology of VHS in Pacific herring. A thorough understanding of these principles provides the basis for identifying risk factors that predispose certain marine fish populations to VHS epizootics, including the lack of population resistance, presence of chronic viral carriers in a population, copious viral shedding by infected individuals, cool water temperatures, limited water circulation patterns, and gregarious host behavioral patterns. Further, these principles are used to define the epizootiological stages of the disease in Pacific herring, including the susceptible (where susceptible individuals predominate a school or subpopulation), enzootic (where infection prevalence and intensity are often below the limits of reasonable laboratory detection), disease amplification (where infection prevalence and intensity increase rapidly), outbreak (often accompanied by host mortalities with high virus loads and active shedding), recovery (in which the mortality rate and virus load decline owing to an active host immune response), and refractory stages (characterized by little or no susceptibility and where viral clearance occurs in most VHS survivors). In addition to providing a foundation for quantitatively assessing the potential risks of future VHS epizootics in Pacific herring, these principles provide insights into the epizootiology of VHS in other fish communities where susceptible species exist.

  11. Low prevalence of Merkel cell polyomavirus with low viral loads in oral and maxillofacial tumours or tumour-like lesions from immunocompetent patients: Absence of Merkel cell polyomavirus-associated neoplasms

    Science.gov (United States)

    TANIO, SHUNSUKE; MATSUSHITA, MICHIKO; KUWAMOTO, SATOSHI; HORIE, YASUSHI; KODANI, ISAMU; MURAKAMI, ICHIRO; RYOKE, KAZUO; HAYASHI, KAZUHIKO

    2015-01-01

    It was recently demonstrated that ~80% of Merkel cell carcinomas (MCCs) harbour a novel polyomavirus, Merkel cell polyomavirus (MCPyV). MCPyV has been detected in various human tissue samples. However, previous studies on the prevalence of MCPyV in oral tumours or tumour-like lesions are incomplete. To address this issue, we measured MCPyV DNA quantity using quantitative polymerase chain reaction (qPCR) in 327 oral tumours or tumour-like lesions and 54 jaw tumours or cyst lesions from 381 immunocompetent patients, as well as in 4 oral lesions from 4 immunosuppressed patients. qPCR revealed a low MCPyV prevalence (25/381, 6.6%) with low viral loads (0.00024-0.026 copies/cell) in oral and maxillofacial tumours and tumour-like lesions from immunocompetent patients. The prevalence was 7/176 (4.0%) in invasive squamous cell carcinomas (SCCs) [2/60 (3.33%) SCCs of the tongue, 4/52 (7.7%) SCCs of the gingiva and 1/19 (5.3%) SCCs of the floor of the mouth], 1/10 (10%) in dysplasias, 1/5 (20%) in adenocarcinomas, 2/13 (15.4%) in adenoid cystic carcinomas, 1/10 (10%) in non-Hodgkin's lymphomas, 3/10 (30%) in lipomas, 3/5 (60%) in neurofibromas, 1/3 (33.3%) in Schwannomas, 2/12 (16.7%) in Warthin's tumours, 2/11 (18.2%) in pyogenic granulomas, 1/14 (7.1%) in radicular cysts and 1/12 (8.3%) in ameloblastomas. The prevalence in lesions from immunosuppressed patients (1/4, 25%) was higher compared with that in lesions from immunocompetent patients (25/381, 6.6%), but the difference was not statistically significant. To the best of our knowledge, this study was the first to report prevalence data of MCPyV in tumours and cysts of the jaws (2/54, 3.7%). These data indicated absence of MCPyV-related tumours or tumour-like lesions in the oral cavity and jaws and suggested that the detected MCPyV DNA was derived from non-neoplastic background tissues with widespread low-level MCPyV infection. PMID:26807237

  12. Essentials of filoviral load quantification.

    Science.gov (United States)

    Cnops, Lieselotte; van Griensven, Johan; Honko, Anna N; Bausch, Daniel G; Sprecher, Armand; Hill, Charles E; Colebunders, Robert; Johnson, Joshua C; Griffiths, Anthony; Palacios, Gustavo F; Kraft, Colleen S; Kobinger, Gary; Hewlett, Angela; Norwood, David A; Sabeti, Pardis; Jahrling, Peter B; Formenty, Pierre; Kuhn, Jens H; Ariën, Kevin K

    2016-07-01

    Quantitative measurement of viral load is an important parameter in the management of filovirus disease outbreaks because viral load correlates with severity of disease, survival, and infectivity. During the ongoing Ebola virus disease outbreak in parts of Western Africa, most assays used in the detection of Ebola virus disease by more than 44 diagnostic laboratories yielded qualitative results. Regulatory hurdles involved in validating quantitative assays and the urgent need for a rapid Ebola virus disease diagnosis precluded development of validated quantitative assays during the outbreak. Because of sparse quantitative data obtained from these outbreaks, opportunities for study of correlations between patient outcome, changes in viral load during the course of an outbreak, disease course in asymptomatic individuals, and the potential for virus transmission between infected patients and contacts have been limited. We strongly urge the continued development of quantitative viral load assays to carefully evaluate these parameters in future outbreaks of filovirus disease.

  13. Sensitive detection of viral transcripts in human tumor transcriptomes.

    Directory of Open Access Journals (Sweden)

    Sven-Eric Schelhorn

    Full Text Available In excess of 12% of human cancer incidents have a viral cofactor. Epidemiological studies of idiopathic human cancers indicate that additional tumor viruses remain to be discovered. Recent advances in sequencing technology have enabled systematic screenings of human tumor transcriptomes for viral transcripts. However, technical problems such as low abundances of viral transcripts in large volumes of sequencing data, viral sequence divergence, and homology between viral and human factors significantly confound identification of tumor viruses. We have developed a novel computational approach for detecting viral transcripts in human cancers that takes the aforementioned confounding factors into account and is applicable to a wide variety of viruses and tumors. We apply the approach to conducting the first systematic search for viruses in neuroblastoma, the most common cancer in infancy. The diverse clinical progression of this disease as well as related epidemiological and virological findings are highly suggestive of a pathogenic cofactor. However, a viral etiology of neuroblastoma is currently contested. We mapped 14 transcriptomes of neuroblastoma as well as positive and negative controls to the human and all known viral genomes in order to detect both known and unknown viruses. Analysis of controls, comparisons with related methods, and statistical estimates demonstrate the high sensitivity of our approach. Detailed investigation of putative viral transcripts within neuroblastoma samples did not provide evidence for the existence of any known human viruses. Likewise, de-novo assembly and analysis of chimeric transcripts did not result in expression signatures associated with novel human pathogens. While confounding factors such as sample dilution or viral clearance in progressed tumors may mask viral cofactors in the data, in principle, this is rendered less likely by the high sensitivity of our approach and the number of biological replicates

  14. Effect of clearance on cartilage tribology in hip hemi-arthroplasty.

    Science.gov (United States)

    Lizhang, Jia; Taylor, Simon D; Jin, Zhongmin; Fisher, John; Williams, Sophie

    2013-12-01

    Hemi-arthroplasty of the hip (an artificial femoral head articulating against the natural acetabulum) is used to treat fractured necks of femur; however, there is evidence that articulation causes erosion of the cartilage, resulting in pain for the patient. Parameters that may influence this cartilage erosion include head material and roughness, clearance between the head and acetabulum and activity levels of the patient. This study has assessed the effect of clearance of hemi-arthroplasty articulations on the contact stress, friction and cartilage deformation in an in vitro tribological simulation of the hemi-arthroplasty joint that applied dynamic loads and motion. It has been demonstrated that peak contact stress increased from 5.6 to 10.6 MPa as radial clearance increased from small (1.8 mm). In all samples, friction factor increased with time and was significantly less with extra-large clearances compared to small (<0.6 mm), medium (0.6-1.2 mm) and large (1.2-1.8 mm) clearances. The cartilage deformation observed was significantly greater in acetabulum samples paired to give small or extra-large clearances compared to those with medium or large clearances.

  15. Viral Marketing Past Present Future

    OpenAIRE

    Nessipbekova, Zarina

    2010-01-01

    The work studies the viral marketing. These are past viral campaigns, viral campaigns today, and evaluates their actuality. The work tries to predict the development of viral marketing on the basis of the research done by the author.

  16. Enhanced clearance of HIV-1-infected cells by broadly neutralizing antibodies against HIV-1 in vivo.

    Science.gov (United States)

    Lu, Ching-Lan; Murakowski, Dariusz K; Bournazos, Stylianos; Schoofs, Till; Sarkar, Debolina; Halper-Stromberg, Ariel; Horwitz, Joshua A; Nogueira, Lilian; Golijanin, Jovana; Gazumyan, Anna; Ravetch, Jeffrey V; Caskey, Marina; Chakraborty, Arup K; Nussenzweig, Michel C

    2016-05-20

    Antiretroviral drugs and antibodies limit HIV-1 infection by interfering with the viral life cycle. In addition, antibodies also have the potential to guide host immune effector cells to kill HIV-1-infected cells. Examination of the kinetics of HIV-1 suppression in infected individuals by passively administered 3BNC117, a broadly neutralizing antibody, suggested that the effects of the antibody are not limited to free viral clearance and blocking new infection but also include acceleration of infected cell clearance. Consistent with these observations, we find that broadly neutralizing antibodies can target CD4(+) T cells infected with patient viruses and can decrease their in vivo half-lives by a mechanism that requires Fcγ receptor engagement in a humanized mouse model. The results indicate that passive immunotherapy can accelerate elimination of HIV-1-infected cells.

  17. Tip Clearance Flows in Turbine Cascades

    Institute of Scientific and Technical Information of China (English)

    Li Wei; Qiao Weiyang; Sun Dawei

    2008-01-01

    This article describes the effects of some factors on the tip clearance flow in axial linear turbine cascades.The measurements of the total pressure loss coefficient are made at the cascade outlets by using a five-hole probe at exit Mach numbers of 0.10,0.14 and 0.19.At each exit Mach number,experiments axe performed at the tip clearance heights of 1.0%,1.5%,2.0%,2.5% and 3.0% of the blade height.The effects of the non-uniform tip clearance height of each blade in the pitchwise direction are also studied.The results show that at a given tip clearance height,generally,total pressure loss rises with exit Mach numbers proportionally.At a fixed exit Mach number,the total pressure loss augments nearly proportionally as the tip clearance height increases.The increased tip clearance heights in the tip regions of two adjacent blades are to be blame for the larger clearance loss of the center blade.Compared to the effects of the tip clearance height,the effects of the exit Mach number and the pitchwise variation of the tip clearance height on the cascade total pressure loss are so less significant to be omitted.

  18. Elastic clearance change in axisymmetric shearing process

    Science.gov (United States)

    Yoshida, Yoshinori

    2016-10-01

    An axisymmetric shearing experiment is conducted for a sheet of low carbon steel and stainless steel. Elastic change in the clearance between punch and die is measured. The increase of the clearance in shearing is confirmed and the influence of sheared material's flow stress on the clearance change is shown. Finite element analysis (FEA) of shearing with Gurson-Tvergaard-Needlman model (GTN model) is conducted for shearing of the carbon steels with rigid tools as a numerical experiment. Burr height is predicted in the FEA and the result is compared with the experimental result. In addition, the influence of the clearance on stress state in the material is investigated.

  19. Progression to AIDS or death in HIV-infected patients initiating cART with CD4<200 cells/µL: the role of CD4 and viral load changes during follow-up

    Directory of Open Access Journals (Sweden)

    S Riera

    2012-11-01

    Full Text Available Purpose of the study: Our aim was to evaluate factors associated with progression to AIDS/death in HIV-infected naïve pts initiating cART with low CD4 counts. Methods: Adult HIV-infected ARV-naïve pts with CD4 <200 who initiated NNRTI or PI-containing regimens between 1998 and 2009, were included. Primary end point was progression to AIDS (a first episode or a new AIDS-defining condition in pts with prior AIDS or death. Kaplan-Meier curves were used to determine progression-free survival and multivariate Cox regression models were used to identify independent predictive factors of progression to AIDS/death. Summary of results: We included 1427 patients (80% men, median age 38 years, 25% IDU, 37% AIDS, 20% HCV between 1998 and 2009. At baseline (BL, median (range CD4 and viral load (VL was 77 (1–199 cells/µL and 170,000 (19–8,750,000 copies/mL, respectively. After a median follow-up 4.6 years, 70% of pts reached CD4>200/µL, 65.2% reached undetectable VL and 268 (19% pts progressed to AIDS/death during follow-up. The probability of AIDS/death at 5 years was 76%, 34%, 3% and 3%, in pts with BL CD4<100/VL>5 log and CD4<200/VL detectable during FU, BL CD4<100/ VL>5 log and CD4<200/VL undetectable during FU, BL CD4<100 and/or VL>5 log and CD4>200/VL undetectable during FU and BL CD4>100/ VL<5 log and CD4>200/VL undetectable during FU, respectively. In the multivariate analysis, several variables were associated with AIDS/death: CD4< 200 during FU (HR 10.89, p<0.001, detectable VL during FU (HR 3.49, p<0.001, age>50 years (HR 1.75, p=0.001, prior AIDS (HR 1.71, p<0.001 and BL VL>5 log (HR 1.45, p=0.011. If only pts without prior AIDS (n=895 were analyzed, the variables independently associated with AIDS/death were: CD4<200 during FU (HR 9.90, p<0.001, detectable VL during FU (HR 2.78, p<0.001 and BL VL>5 log (HR 1.62, p=0.016. Conclusions: In immunosuppressed patients initiating cARV therapy, not reaching CD4>200/µL during FU was the strongest

  20. The Immune Response in Measles: Virus Control, Clearance and Protective Immunity.

    Science.gov (United States)

    Griffin, Diane E

    2016-10-12

    Measles is an acute systemic viral infection with immune system interactions that play essential roles in multiple stages of infection and disease. Measles virus (MeV) infection does not induce type 1 interferons, but leads to production of cytokines and chemokines associated with nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) signaling and activation of the NACHT, LRR and PYD domains-containing protein (NLRP3) inflammasome. This restricted response allows extensive virus replication and spread during a clinically silent latent period of 10-14 days. The first appearance of the disease is a 2-3 day prodrome of fever, runny nose, cough, and conjunctivitis that is followed by a characteristic maculopapular rash that spreads from the face and trunk to the extremities. The rash is a manifestation of the MeV-specific type 1 CD4⁺ and CD8⁺ T cell adaptive immune response with lymphocyte infiltration into tissue sites of MeV replication and coincides with clearance of infectious virus. However, clearance of viral RNA from blood and tissues occurs over weeks to months after resolution of the rash and is associated with a period of immunosuppression. However, during viral RNA clearance, MeV-specific antibody also matures in type and avidity and T cell functions evolve from type 1 to type 2 and 17 responses that promote B cell development. Recovery is associated with sustained levels of neutralizing antibody and life-long protective immunity.

  1. TNFα Impairs Rhabdoviral Clearance by Inhibiting the Host Autophagic Antiviral Response.

    Science.gov (United States)

    Espín-Palazón, Raquel; Martínez-López, Alicia; Roca, Francisco J; López-Muñoz, Azucena; Tyrkalska, Sylwia D; Candel, Sergio; García-Moreno, Diana; Falco, Alberto; Meseguer, José; Estepa, Amparo; Mulero, Victoriano

    2016-06-01

    TNFα is a pleiotropic pro-inflammatory cytokine with a key role in the activation of the immune system to fight viral infections. Despite its antiviral role, a few viruses might utilize the host produced TNFα to their benefit. Some recent reports have shown that anti-TNFα therapies could be utilized to treat certain viral infections. However, the underlying mechanisms by which TNFα can favor virus replication have not been identified. Here, a rhabdoviral infection model in zebrafish allowed us to identify the mechanism of action by which Tnfa has a deleterious role for the host to combat certain viral infections. Our results demonstrate that Tnfa signals through its receptor Tnfr2 to enhance viral replication. Mechanistically, Tnfa does not affect viral adhesion and delivery from endosomes to the cytosol. In addition, the host interferon response was also unaffected by Tnfa levels. However, Tnfa blocks the host autophagic response, which is required for viral clearance. This mechanism of action provides new therapeutic targets for the treatment of SVCV-infected fish, and advances our understanding of the previously enigmatic deleterious role of TNFα in certain viral infections.

  2. TNFα Impairs Rhabdoviral Clearance by Inhibiting the Host Autophagic Antiviral Response.

    Directory of Open Access Journals (Sweden)

    Raquel Espín-Palazón

    2016-06-01

    Full Text Available TNFα is a pleiotropic pro-inflammatory cytokine with a key role in the activation of the immune system to fight viral infections. Despite its antiviral role, a few viruses might utilize the host produced TNFα to their benefit. Some recent reports have shown that anti-TNFα therapies could be utilized to treat certain viral infections. However, the underlying mechanisms by which TNFα can favor virus replication have not been identified. Here, a rhabdoviral infection model in zebrafish allowed us to identify the mechanism of action by which Tnfa has a deleterious role for the host to combat certain viral infections. Our results demonstrate that Tnfa signals through its receptor Tnfr2 to enhance viral replication. Mechanistically, Tnfa does not affect viral adhesion and delivery from endosomes to the cytosol. In addition, the host interferon response was also unaffected by Tnfa levels. However, Tnfa blocks the host autophagic response, which is required for viral clearance. This mechanism of action provides new therapeutic targets for the treatment of SVCV-infected fish, and advances our understanding of the previously enigmatic deleterious role of TNFα in certain viral infections.

  3. 北京地区男男性接触人类免疫缺陷病毒感染者人类白细胞抗原-Ⅰ类分子多态性对病毒载量的影响%The influence of human leucocyte antigen-Ⅰ polymorphisms on plasma viral load in human immunodeficiency virus infected male homosexual population in Beijing

    Institute of Scientific and Technical Information of China (English)

    张欣; 王熠; 王爽; 李伟华; 胡文静; 赵丹彤; 闫惠平

    2013-01-01

    目的 分析北京地区男男性接触人群HIV感染者人类白细胞抗原(HLA)-Ⅰ的多态性及其对病毒载量的影响.方法 用序列特异性引物-聚合酶链反应(SSP-PCR)对157例慢性HIV感染者的HLA-A、HLA-B、HLA-C等位基因分型,同时检测HIV载量.正态分布的计量资料采用单因素或多因素方差分析,非正态分布的计量资料用Mann-Whitney U检验.结果 157例HIV感染者中,HLA-B携带Bw4表位簇个数与低病毒载量有关(F=3.01,P=0.045),HLA-B携带Bw4/4纯合子的感染者HIV载量为(4.19±0.76) lg IU/mL,Bw6/6纯合子的感染者为(4.63±0.74) lg IU/mL(t=2.27,P=0.010).HLA-A、HLA-B同时携带3个Bw4的感染者HIV载量为(3.92±0.97)lg IU/mL,显著低于携带1个Bw4的感染者HIV载量(4.54±0.88) lg IU/mL和不携带Bw4者HIV载量(4.60±0.72) lg IU/mL(t=2.11,P=0.039;t=2.53,P=0.015).HLA-Ⅰ类分子(HLA-A、HLA-B、HLA-C)均携带杂合子的感染者,其病毒载量与任一座位携带纯合子的感染者病毒载量比较,差异无统计学意义.HLA-Ⅰ类分子均携带杂合子且HLA-B携带Bw4/4纯合子的感染者其HIV载量中位数为4.09 lg IU/mL,低于HLA-B携带Bw6/6纯合子感染者的4.55 lg IU/mL(U=210.50,P=0.041).携带A30/B13/C06单体型或A33/B58/C03单体型的感染者其HIV载量与不携带A30/B13/C06单体型或A33/B58/C03单体型感染者比较,差异无统计学意义(t=0.40,P=0.69;t=0.68,P=0.49).结论 HIV感染者HLA-B携带Bw4/4纯合子与低病毒载量有关,且HLA Ⅰ类分子携带杂合子的个体可受HLA-B携带Bw4/4纯合子影响,这些HIV感染者病毒载量更低.%Objective To analyze the influence of the polymorphisms of human leucocyte antigen (HLA)-Ⅰ molecule and the effects on plasma viral load of human immunodeficiency virus (HIV) infected male homosexual population in Beijing.Methods The HLA-A,HLA-B,HLA-C allele were typed by sequence specific primer-polymerase chain reaction (SSP-PCR),and viral load was detected in 157 chronic HIV infected

  4. Effects of lime juice on malaria parasite clearance.

    Science.gov (United States)

    Adegoke, S A; Oyelami, O A; Olatunya, O S; Adeyemi, L A

    2011-10-01

    One hundred and twenty children with acute uncomplicated malaria who were managed at the children's outpatient department of the Wesley Guild Hospital, Ilesa (a unit of Obafemi Awolowo University Teaching Hospitals' Complex, Ile-Ife, Osun state, Nigeria) were recruited into the study to determine the effects of lime juice on malaria parasite clearance. These children were randomized into treatment with World Health Organization recommended antimalarials (artemisinin combination therapy, ACT) either alone or with lime juice. Nine of them were lost to follow-up, four were in the group that were managed with ACT and lime, and five in the group that were managed on ACT alone. The average (SD) time to achieve >75% reduction in parasite load was significantly lower in patients on ACT and lime; 30.5 ± 2.4 h against 38.6 ± 3.3 h for those on ACT alone (p lime juice achieved complete parasite clearance by 72 h of therapy (p = 0.007), ten (18.2%) patients without lime had early treatment failure (p = 0.003). There were no side effects with the use of lime juice. It may therefore be inferred, from this preliminary work, that lime juice when used with the appropriate antimalarial may enhance malaria parasite clearance especially in those with uncomplicated malaria.

  5. Critical evaluation of mannitol determination and clearance

    NARCIS (Netherlands)

    Dorhout Mees, E.J.; Kampman, J.W.; Verschure, J.C.M.

    1958-01-01

    The mannitol clearance in normal persons was found to be lower than is indicated by most authors. The method of the blood collection appeared to have an unexpected influence on the clearance values obtained. In this manner at least some of the discrepancies can be explained.

  6. 30 CFR 56.7018 - Hand clearance.

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Hand clearance. 56.7018 Section 56.7018 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE SAFETY AND... Drilling § 56.7018 Hand clearance. Persons shall not hold the drill steel while collaring holes, or...

  7. 30 CFR 57.7018 - Hand clearance.

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Hand clearance. 57.7018 Section 57.7018 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE SAFETY AND... Drilling-Surface Only § 57.7018 Hand clearance. Persons shall not hold the drill steel while...

  8. 15 CFR 752.15 - Export clearance.

    Science.gov (United States)

    2010-01-01

    ... 15 Commerce and Foreign Trade 2 2010-01-01 2010-01-01 false Export clearance. 752.15 Section 752.15 Commerce and Foreign Trade Regulations Relating to Commerce and Foreign Trade (Continued) BUREAU... COMPREHENSIVE LICENSE § 752.15 Export clearance. (a) Shipper's Export Declaration (SED) or Automated...

  9. 30 CFR 57.7028 - Hand clearance.

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Hand clearance. 57.7028 Section 57.7028 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE SAFETY AND... Drilling-Underground Only § 57.7028 Hand clearance. Persons shall not rest their hands on the chuck...

  10. 19 CFR 122.77 - Clearance certificate.

    Science.gov (United States)

    2010-04-01

    ... 19 Customs Duties 1 2010-04-01 2010-04-01 false Clearance certificate. 122.77 Section 122.77 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT OF THE TREASURY AIR COMMERCE REGULATIONS Documents Required for Clearance and Permission To Depart;...

  11. Numerical Simulation on the Effect of Tip Clearance Size on Unsteadiness in Tip Clearance Flow

    Institute of Scientific and Technical Information of China (English)

    Juan Du; Feng Lin; Hongwu Zhang; Jingyi Chen

    2008-01-01

    Unsteadiness of tip clearance flow with three different tip clearance sizes is numerically investigated in this paper. NASA Rotor 67 is chosen as the computational model. It is found that among all the simulated cases, the un-steadiness exists when the size of the tip clearance is equal to or larger than design tip clearance size. The relative total pressure coefficient contours indicate that region of influence by tip leakage flow augments with the increase of tip clearance size at a fixed mass flow rate. Root Mean Square contours of static pressure distribution in the rotor tip region are provided to illustrate that for design tip clearance (1.1% tip chord) the strongest fluctuating region is located on pressure side of blade near leading edge, while for the larger tip clearance (2.2% tip chord), it is in the region of the interaction between the shock wave and the tip leakage flow.

  12. Heteropolymers: A New Class of Therapeutics for Treating Lethal Bacterial and Viral Infections

    Science.gov (United States)

    2004-11-17

    tularensis (Tularemia) • Clostridium botulinum • Poxviruses (Smallpox) • Viral hemorrhagic fevers Filoviruses (Ebola, Marburg) Arenaviruses...viral challenges we developed challenge models in a transgenic mouse (TgN hCR1) that expresses human CR1 on the surface of their RBCs.6 While mice...Klickstein L., Spitalny G. L., Finberg R. W. 2004. A transgenic mouse model for studying the clearance of blood-borne pathogens via human complement receptor

  13. [Emergent viral infections

    NARCIS (Netherlands)

    Galama, J.M.D.

    2001-01-01

    The emergence and re-emergence of viral infections is an ongoing process. Large-scale vaccination programmes led to the eradication or control of some viral infections in the last century, but new viruses are always emerging. Increased travel is leading to a rise in the importation of exotic infecti

  14. Viral Haemorrhagic Septicaemia Virus

    DEFF Research Database (Denmark)

    Olesen, Niels Jørgen; Skall, Helle Frank

    2013-01-01

    This chapter covers the genetics (genotypes and serotypes), clinical signs, host species, transmission, prevalence, diagnosis, control and prevention of viral haemorrhagic septicaemia virus.......This chapter covers the genetics (genotypes and serotypes), clinical signs, host species, transmission, prevalence, diagnosis, control and prevention of viral haemorrhagic septicaemia virus....

  15. Evaluation for quantitative methods of HBV DNA in serum with very high viral loads%高病毒载量血清HBV DNA定量方法的评价

    Institute of Scientific and Technical Information of China (English)

    李雷; 冯振华; 许碧云; 顾光煜; 张葵; 周乙华

    2012-01-01

    Objective To explore whether quantitative standard curve may be directly extended to determine HBV DNA level in the cases of very high viral loads which was over the upper limit of detection range. Methods A total of 30 serum samples were included. The HBV DNA levels of all the samples were more than 3×107 IU/ml detected by fluorescent quantification kit purchased from Shanghai Shenyou Company. Each samples was quantitatively retested for three times. Both the serum samples and the HBV DNA extracted from serum were further measured in 10-, 100- and 1 000-fold dilution, respectively. After logarithmic conversion the quantitative values were statistically analyzed. Results When the quantitative data of HBV DNA were expressed as logarithm values, the inter-class correlation coefficient was 0.356 (F = 2.66, P 0. 05 ), and the maximum differences were less than 1 in each sample. Conclusion In the determination of HBV DNA by using domestic reagents, direct extension of the quantitative standard curve may be acceptable even if the level of HBV DNA was over the upper limit of detection. For accurate quantification, it is suggested that the serum-extracted DNA with 100-fold dilution should be used as the test materials.%目的 探讨血清HBV DNA定量检测结果高于检测上限时,能否直接延伸标准曲线,用于HBV DNA定量分析.方法 以上海申友生物公司HBV DNA荧光定量检测试剂盒为例,选择HBV DNA>3×107 IU/mL的血清标本30例.每例血清在3个不同时间点提取DNA,或将血清以10、100和1000倍稀释后提取DNA,或将未稀释血清提取的DNA以10、100和1000倍稀释后进行HBV DNA定量检测,检测结果以10为底数进行对数转换后进行统计学分析.结果 经对数转换,3个不同时间点HBV DNA定量检测结果的组间相关系数为0.356(F=2.66,P<0.01);36.7% (11/30)的标本最大差值<0.5,60.0%(18/30)介于0.5~1.0,3.3% (1/30)达1.01;血清稀释后定量检测HBV DNA,96.7%(29/30)

  16. Relação entre a carga viral de HPV oncogênico determinada pelo método de captura híbrida e o diagnóstico citológico de lesões de alto grau Association between high-risk human papillomavirus DNA load detected by hybrid capture II and high-grade precursor lesions of cervical cancer in women

    Directory of Open Access Journals (Sweden)

    Siumara Tulio

    2007-02-01

    Full Text Available INTRODUÇÃO: O papilomavírus humano (HPV é o principal fator de risco para as neoplasias intra-epiteliais cervicais (NIC e o câncer cervical. OBJETIVO: O objetivo deste estudo é avaliar se há associação entre a carga viral de HPV oncogênico (alto risco, determinada por meio do teste molecular captura híbrida II (CH II, e o diagnóstico de lesões de alto grau (NIC II/III. MATERIAL E MÉTODOS: Foram analisadas 982 amostras cervicovaginais de exames ginecológicos de rotina, obtidas pelos métodos Papanicolaou convencional e/ou citologia em base líquida (DNA-Citoliq-Digene. Os resultados foram confirmados utilizando-se o método de captura híbrida (CH [Digene] para detecção de DNA/HPV de alto grau. Os resultados com valor > 1 pg/ml foram considerados positivos, e esses foram divididos em dois grupos: 1. carga viral 100 pg/ml. RESULTADOS: Dos 210 (21,4% casos diagnosticados como NIC I, 152 (72,4% foram positivos para HPV de alto risco por CH II. Desses, 101 (66,4% apresentaram carga viral > 100 pg/ml. O diagnóstico de NIC II ou III foi confirmado por CH II de alto risco em 86 (43,6% casos, contudo, entre esses, em 53 (61,6% a carga viral detectada foi > 100 pg/ml. DISCUSSÃO E CONCLUSÃO: Nossos resultados demonstram que há uma clara associação entre o valor da carga viral determinada pelo método CH II (versão 1 e o grau das lesões precursoras de câncer. Pacientes com carga viral superior a 100 µg/ml devem ser monitoradas periodicamente.INTRODUCTION: Infection with oncogenic human papilloma virus (HPV has been established as the main etiologic agent for cervical cancer and of cervical intraepithelial neoplasia (CIN. OBJECTIVE: To determine the association between viral loads of the high risk HPV using the hybrid capture II (HC II system and CIN lesion stage. MATERIAL AND METHOD: A total of 982 women with diagnosis of negative or of CIN I-III with Pap or liquid-based cytology (DNA-Citoliq-Digene were included. HC II testing

  17. Viral-templated Palladium Nanocatalysts

    Science.gov (United States)

    Yang, Cuixian

    Despite recent progress on nanocatalysis, there exist several critical challenges in simple and readily controllable nanocatalyst synthesis including the unpredictable particle growth, deactivation of catalytic activity, cumbersome catalyst recovery and lack of in-situ reaction monitoring. In this dissertation, two novel approaches are presented for the fabrication of viral-templated palladium (Pd) nanocatalysts, and their catalytic activities for dichromate reduction reaction and Suzuki Coupling reaction were thoroughly studied. In the first approach, viral template based bottom-up assembly is employed for the Pd nanocatalyst synthesis in a chip-based format. Specifically, genetically displayed cysteine residues on each coat protein of Tobacco Mosaic Virus (TMV) templates provide precisely spaced thiol functionalities for readily controllable surface assembly and enhanced formation of catalytically active Pd nanoparticles. Catalysts with the chip-based format allow for simple separation and in-situ monitoring of the reaction extent. Thorough examination of synthesis-structure-activity relationship of Pd nanoparticles formed on surface-assembled viral templates shows that Pd nanoparticle size, catalyst loading density and catalytic activity of viral-templated Pd nanocatalysts can be readily controlled simply by tuning the synthesis conditions. The viral-templated Pd nanocatalysts with optimized synthesis conditions are shown to have higher catalytic activity per unit Pd mass than the commercial Pd/C catalysts. Furthermore, tunable and selective surface assembly of TMV biotemplates is exploited to control the loading density and location of Pd nanocatalysts on solid substrates via preferential electroless deposition. In addition, the catalytic activities of surface-assembled TMV-templated Pd nanocatalysts were also investigated for the ligand-free Suzuki Coupling reaction under mild reaction conditions. The chip-based format enables simple catalyst separation and

  18. Necroptosis Promotes Staphylococcus aureus Clearance by Inhibiting Excessive Inflammatory Signaling

    Directory of Open Access Journals (Sweden)

    Kipyegon Kitur

    2016-08-01

    Full Text Available Staphylococcus aureus triggers inflammation through inflammasome activation and recruitment of neutrophils, responses that are critical for pathogen clearance but are associated with substantial tissue damage. We postulated that necroptosis, cell death mediated by the RIPK1/RIPK3/MLKL pathway, would function to limit pathological inflammation. In models of skin infection or sepsis, Mlkl−/− mice had high bacterial loads, an inability to limit interleukin-1b (IL-1b production, and excessive inflammation. Similarly, mice treated with RIPK1 or RIPK3 inhibitors had increased bacterial loads in a model of sepsis. Ripk3−/− mice exhibited increased staphylococcal clearance and decreased inflammation in skin and systemic infection, due to direct effects of RIPK3 on IL-1b activation and apoptosis. In contrast to Casp1/4−/− mice with defective S. aureus killing, the poor outcomes of Mlkl−/− mice could not be attributed to impaired phagocytic function. We conclude that necroptotic cell death limits the pathological inflammation induced by S. aureus.

  19. New treatment strategies for chronic hepatitis B: Viral, genetic and immunological factors predicting treatment outcome

    NARCIS (Netherlands)

    de Niet, A.

    2016-01-01

    In dit proefschrift onderzochten we de effectiviteit van combinatie therapie bij chronische hepatitis B patiënten met een hoge en een lage virale load. Na behandeling met peg-interferon en adefovir in patiënten met een hoge virale load werd een relatief hoog percentage van HBsAg verlies gezien in zo

  20. Viral marketing on the Internet

    OpenAIRE

    Štverák, Martin

    2008-01-01

    Thesis provides an overview of viral marketing. It describes the process by which you can be inspired to implement viral campaign. The thesis includes analysis of specific viral Web project. The aim of this thesis is to create a breakdown of the various components of viral marketing, to establish conditions that should be satisfied for the viral marketing to success, suggesting how to use viral marketing on social network Facebook and evaluate the various components of this service for the pr...

  1. Glial K(+) Clearance and Cell Swelling

    DEFF Research Database (Denmark)

    Macaulay, Nanna; Zeuthen, Thomas

    2012-01-01

    space into the glial cell are debated. Although spatial buffer currents may occur, their quantitative contribution to K(+) clearance is uncertain. The concept of spatial buffering of K(+) precludes intracellular K(+) accumulation and is therefore (i) difficult to reconcile with the K(+) accumulation...... repeatedly observed in glial cells during K(+) clearance and (ii) incompatible with K(+)-dependent glial cell swelling. K(+) uptake into non-voltage clamped cultured glial cells is carried out by the Na(+)/K(+)-ATPase and the Na(+)/K(+)/Cl(-) cotransporter in combination. In brain slices and intact optic...... nerve, however, only the Na(+)/K(+)-ATPase has been demonstrated to be involved in stimulus-evoked K(+) clearance. The glial cell swelling associated with K(+) clearance is prevented under conditions that block the activity of the Na(+)/K(+)/Cl(-) cotransporter. The Na(+)/K(+)/Cl(-) cotransporter...

  2. Plasma Creatinine Clearance in the Dog

    Science.gov (United States)

    Frazier, Loy W.

    1977-01-01

    Lists materials and methods for an experiment that demonstrates the concept of glomerular filtration rate (GFR) using anesthesized dogs. In the dog, GFR is equivalent to the renal plasma clearance of exogenous creatinine. (CS)

  3. Determination of tooth clearances at trochoidal pump

    OpenAIRE

    Ivanović, Lozica T.; Erić, Milan D.; Stojanović, Blaža Ž.; id_orcid 0000-0003-4790-2856; Ilić, Andreja B.

    2011-01-01

    The paper describes the development of a mathematical model of trochoidal gearing with clearances. Gearing of a trochoidal pump's gear set with an outer gear having one gear tooth more than an inner gear is analyzed. The inner gear tooth profile is described by peritrochoidal equidistance and the outer gear profile by a circular arc. Upon the basic principles of ideal profile generation, a mathematical model of gearing with clearances is developed. Using an analytical model, the calculation o...

  4. Viral Gastroenteritis (Stomach Flu)

    Science.gov (United States)

    ... There's often no specific medical treatment for viral gastroenteritis. Antibiotics aren't effective against viruses, and overusing them can contribute to the development of antibiotic-resistant strains of bacteria. Treatment initially consists of self-care measures. To ...

  5. Viral quasispecies complexity measures.

    Science.gov (United States)

    Gregori, Josep; Perales, Celia; Rodriguez-Frias, Francisco; Esteban, Juan I; Quer, Josep; Domingo, Esteban

    2016-06-01

    Mutant spectrum dynamics (changes in the related mutants that compose viral populations) has a decisive impact on virus behavior. The several platforms of next generation sequencing (NGS) to study viral quasispecies offer a magnifying glass to study viral quasispecies complexity. Several parameters are available to quantify the complexity of mutant spectra, but they have limitations. Here we critically evaluate the information provided by several population diversity indices, and we propose the introduction of some new ones used in ecology. In particular we make a distinction between incidence, abundance and function measures of viral quasispecies composition. We suggest a multidimensional approach (complementary information contributed by adequately chosen indices), propose some guidelines, and illustrate the use of indices with a simple example. We apply the indices to three clinical samples of hepatitis C virus that display different population heterogeneity. Areas of virus biology in which population complexity plays a role are discussed.

  6. Decrease in viral load at weeks 12 and 24 in patients with chronic hepatitis B treated with lamivudine or adefovir predicts virological response at week 48 En pacientes con hepatitis crónica B tratados con lamivudina y adefovir el descenso de la viremia en las semanas 12 y 24 tiene valor predictivo de respuesta virológica

    Directory of Open Access Journals (Sweden)

    E. Llop

    2009-11-01

    Full Text Available Aim: the aim of our study was to evaluate the decrease in viral load (VL that is able to predict antiviral treatment response at one year in patients with chronic hepatitis B. Methods: the clinical records of 66 patients, 31 treated with lamivudine (LAM and 35 treated with adefovir (ADF, were retrospectively reviewed. We measured viral DNA at months 1, 3 and 6. Results: the LAM group showed virological response (VR in 51.6% of patients. Baseline VL was higher in non responders (5.37 ± 1.16 vs. 7.01 ± 1.05; p < 0.001. Responders showed a higher percentage of VL decrease at month 3 from baseline (49.2 vs. 38.3%; p = 0.03. We designed a ROC curve and established a cutoff point for decrease of 30% that had 80% of negative predictive value (NPV. The ADF group showed VR in 57.1% of patients. Baseline VL was higher in nonresponders (4.67 ± 1.22 vs. 5.78 ± 1.34; p = 0.01. We observed a significant decrease in VL (log at months 3 (2.6 ± 1.1 vs. 1.3 ± 1.3; p = 0.03 and 6 (2.6 ± 1.2 vs. 1.3 ± 1.2; p = 0.006. The percentage of decrease of VL from baseline was also statistically significant. We created ROC curves at months 3 and 6, and established the best cutoff points. At month 6 a decrease of 1 log in VL had a NPV of 80%, and a decrease of 20% in VL from baseline had 100% NPV. Conclusion: the decrease in viral DNA at weeks 12 and 24 can predict VR at one year in patients with chronic hepatitis B treated with LAM or ADF. This could optimize treatment.

  7. Prospects for cannabinoid therapies in viral encephalitis.

    Science.gov (United States)

    Solbrig, Marylou V; Fan, Yijun; Hazelton, Paul

    2013-11-06

    Cannabinoids are promising therapies to support neurogenesis and decelerate disease progression in neuroinflammatory and degenerative disorders. Whether neuroprotective effects of cannabinoids are sustainable during persistent viral infection of the CNS is not known. Using a rodent model of chronic viral encephalitis based on Borna Disease (BD) virus, in which 1 week treatment with the general cannabinoid WIN 55,212-2 has been shown to be neuroprotective (Solbrig et al., 2010), we examine longer term (2 week treatment) effects of a general (CB1 and CB2) cannabinoid receptor agonist WIN55,212-2 (1mg/kg ip twice per day) or a specific (CB2) cannabinoid receptor agonist HU-308 (5mg/kg ip once daily) on histopathology, measures of frontostriatal neurogenesis and gliogenesis, and viral load. We find that WIN and HU-308 differ in their ability to protect new BrdU(+) cells. The selective CB2 agonist HU increases BrdU(+) cells in prefrontal cortex (PFC), significantly increases BrdU(+) cells in striatum, differentially regulates polydendrocytes vs. microglia/macrophages, and reduces immune activation at a time WIN-treated rats appear tolerant to the anti-inflammatory effect of their cannabinoid treatment. WIN and HU had little direct viral effect in PFC and striatum, yet reduced viral signal in hippocampus. Thus, HU-308 action on CB2 receptors, receptors known to be renewed during microglia proliferation and action, is a nontolerizing mechanism of controlling CNS inflammation during viral encephalitis by reducing microglia activation, as well as partially limiting viral infection, and uses a nonpsychotropic cannabinoid agonist.

  8. NCBI viral genomes resource.

    Science.gov (United States)

    Brister, J Rodney; Ako-Adjei, Danso; Bao, Yiming; Blinkova, Olga

    2015-01-01

    Recent technological innovations have ignited an explosion in virus genome sequencing that promises to fundamentally alter our understanding of viral biology and profoundly impact public health policy. Yet, any potential benefits from the billowing cloud of next generation sequence data hinge upon well implemented reference resources that facilitate the identification of sequences, aid in the assembly of sequence reads and provide reference annotation sources. The NCBI Viral Genomes Resource is a reference resource designed to bring order to this sequence shockwave and improve usability of viral sequence data. The resource can be accessed at http://www.ncbi.nlm.nih.gov/genome/viruses/ and catalogs all publicly available virus genome sequences and curates reference genome sequences. As the number of genome sequences has grown, so too have the difficulties in annotating and maintaining reference sequences. The rapid expansion of the viral sequence universe has forced a recalibration of the data model to better provide extant sequence representation and enhanced reference sequence products to serve the needs of the various viral communities. This, in turn, has placed increased emphasis on leveraging the knowledge of individual scientific communities to identify important viral sequences and develop well annotated reference virus genome sets.

  9. Immigration and viral hepatitis.

    Science.gov (United States)

    Sharma, Suraj; Carballo, Manuel; Feld, Jordan J; Janssen, Harry L A

    2015-08-01

    WHO estimates reveal that the global prevalence of viral hepatitis may be as high as 500 million, with an annual mortality rate of up to 1.3 million individuals. The majority of this global burden of disease is borne by nations of the developing world with high rates of vertical and iatrogenic transmission of HBV and HCV, as well as poor access to healthcare. In 2013, 3.2% of the global population (231 million individuals) migrated into a new host nation. Migrants predominantly originate from the developing countries of the south, into the developed economies of North America and Western Europe. This mass migration of individuals from areas of high-prevalence of viral hepatitis poses a unique challenge to the healthcare systems of the host nations. Due to a lack of universal standards for screening, vaccination and treatment of viral hepatitis, the burden of chronic liver disease and hepatocellular carcinoma continues to increase among migrant populations globally. Efforts to increase case identification and treatment among migrants have largely been limited to small outreach programs in urban centers, such that the majority of migrants with viral hepatitis continue to remain unaware of their infection. This review summarizes the data on prevalence of viral hepatitis and burden of chronic liver disease among migrants, current standards for screening and treatment of immigrants and refugees, and efforts to improve the identification and treatment of viral hepatitis among migrants.

  10. Treatment of viral encephalitis.

    Science.gov (United States)

    Domingues, Renan Barros

    2009-03-01

    Several viruses may cause central nervous system diseases with a broad range of clinical manifestations. The time course of the viral encephalitis can be acute, subacute, or chronic. Pathologically there are encephalitis with direct viral entry into the CNS in which brain parenchyma exhibits neuronal damaging and viral antigens and there are postinfectious autoimmune encephalitis associated with systemic viral infections with brain tissue presenting perivascular aggregation of immune cells and myelin damaging. Some virus affect previously healthy individuals while others produce encephalitis among imunocompromised ones. Factors such evolving lifestyles and ecological changes have had a considerable impact on the epidemiology of some viral encephalitis [e.g. West-Nile virus, and Japanese B virus]. Citomegalovirus and JC virus are examples of infections of the brain that have been seen more frequently because they occur in immunocompromised patients. In the other hand many scientific achievements in neuroimaging, molecular diagnosis, antiviral therapy, immunomodulatory treatments, and neurointensive care have allowed more precise and earlier diagnoses and more efficient treatments, resulting in improved outcomes. In this article, we will present the current drug options in the management of the main acute and chronic viral infection of the central nervous system of immunocompetent and immunocompromised adults, focusing on drugs mechanisms of action, efficacy, and side effects. The early diagnosis and correct management of such diseases can reduce mortality and neurological sequelae; however, even with recent treatment advances, potentially devastating outcomes are still possible.

  11. Lower metabolic clearance of tizanidine in Japanese subjects.

    Science.gov (United States)

    Momo, Kenji; Homma, Masato; Kohda, Yukinao

    2013-12-01

    Our aim was to determine whether metabolic clearance, renal clearance, or both elimination pathways contribute to ethnic differences in tizanidine clearance, which is ~ 2-fold higher in Caucasians than in Asians. The pharmacokinetic parameters of tizanidine in 9 healthy male Japanese subjects were compared with those of Caucasians in previous studies. Metabolic clearance of tizanidine was lower in Japanese than in Caucasian subjects (5.9 vs. 8.1 - 10.9 l/h/kg), although renal clearances were similar (0.040 vs. 0.047 - 0.055 l/h/kg). The results suggest that ethnic differences in tizanidine clearance are due to differences in metabolic clearance.

  12. A study of the influence of bearing clearance on lateral coupled shaft/disk rotordynamics

    Science.gov (United States)

    Flowers, George T.; Wu, Fang S.

    1992-06-01

    This study examines the influence of bearing clearance on the dynamical behavior of a rotating, flexible disk/shaft system. Most previous work in nonlinear rotordynamics has tended to concentrate separately on shaft vibration or on bladed disk vibration, neglecting the coupling dynamics between them. The current work examines the important rotordynamical behavior of coupled disk/shaft dynamics. A simplified nonlinear model is developed for lateral vibration of a rotor system with a bearing clearance nonlinearity. The steady-state dynamical behavior of this system is explored using numerical simulation and limit cycle analysis. It is demonstrated that bearing clearance effects can produce superharmonic vibration that may serve to excite high amplitude disk vibration. Such vibration could lead to significantly increased bearing loads and catastrophic failure of blades and disks. In addition, multi-valued responses and aperiodic behavior was observed.

  13. Viral induced demyelination.

    Science.gov (United States)

    Stohlman, S A; Hinton, D R

    2001-01-01

    Viral induced demyelination, in both humans and rodent models, has provided unique insights into the cell biology of oligodendroglia, their complex cell-cell interactions and mechanisms of myelin destruction. They illustrate mechanisms of viral persistence, including latent infections in which no infectious virus is readily evident, virus reactivation and viral-induced tissue damage. These studies have also provided excellent paradigms to study the interactions between the immune system and the central nervous system (CNS). Although of interest in their own right, an understanding of the diverse mechanisms used by viruses to induce demyelination may shed light into the etiology and pathogenesis of the common demyelinating disorder multiple sclerosis (MS). This notion is supported by the persistent view that a viral infection acquired during adolescence might initiate MS after a long period of quiescence. Demyelination in both humans and rodents can be initiated by infection with a diverse group of enveloped and non-enveloped RNA and DNA viruses (Table 1). The mechanisms that ultimately result in the loss of CNS myelin appear to be equally diverse as the etiological agents capable of causing diseases which result in demyelination. Although demyelination can be a secondary result of axonal loss, in many examples of viral induced demyelination, myelin loss is primary and associated with axonal sparing. This suggests that demyelination induced by viral infections can result from: 1) a direct viral infection of oligodendroglia resulting in cell death with degeneration of myelin and its subsequent removal; 2) a persistent viral infection, in the presence or absence of infectious virus, resulting in the loss of normal cellular homeostasis and subsequent oligodendroglial death; 3) a vigorous virus-specific inflammatory response wherein the virus replicates in a cell type other than oligodendroglia, but cytokines and other immune mediators directly damage the

  14. 人类博卡病毒载量与儿童呼吸道感染临床特征的相关性%The correlation study of viral load of human bocavirus and clinical features of children with acute respiratory tract infection

    Institute of Scientific and Technical Information of China (English)

    尹芳; 周卫芳; 王美娟; 严永东; 季伟

    2014-01-01

    导致患儿细胞免疫功能紊乱,且HBoV载量愈高,愈能引起婴幼儿发生喘息.对于HBoV低病毒载量的患儿,要考虑存在其他病原体混合感染可能.%Objective To investigate the detection of human bocavirus (HBoV) in children with acute respiratory infection and to explore the relationship between viral load and clinical characteristics of acute respiratory infection in children.Methods A total of 4 501 nasopharyngeal secretion samples were collected from hospitalized children with acute respiratory infection from January 2013 to June 2013.HBoV-positive children were divided into simple infection group and mixed infection group.Children with HBoV DNA≥1 × 104 copy/mL were categorized into high viral load group,while those with HBoV DNA <1 × 104 copy/mL were categorized into low viral load group.HBoV was determined by fluorescence quantitative polymerase chain reaction (PCR).Respiratory syncytial virus (RSV),influenza virus (Inf)-A,Inf-B,parainfluenza virus (Pinf)-Ⅰ 、Pinf-Ⅱ 、Pinf-Ⅲ and adeno virus antigen were detected by direct antigen-specific immunofluorescence assays.Mycoplasm Pnuemonia was detected by real-time fluorescence quantitative PCR.Serum mycoplasma antibodies were detected by enzyme-linked immunosorbent assay (ELISA).Bacteria was detected by sputum culture.Over the same period,23 children undergoing elective inguinal hernia operation with no respiratory infection or fever were considered as control group.The percentage of peripheral blood T lymphocyte subsets were tested by flow cytometry.Inter-group differences were compared using Chi-square test or Fisher exact test.Viral loads were compared using Mann-Whitney test.Results Two hundred and twenty-two HBoV-positive cases were detected with a positive rate of 5.41% (222/4 105),33.33% (74/222) of which were with high viral load and 66.67% (148/222) were with low viral load.There was a high incidence in the age group of 1-2 years.The simple HBoV infection

  15. Bile acids for viral hepatitis

    DEFF Research Database (Denmark)

    Chen, Weikeng; Liu, J; Gluud, C

    2003-01-01

    The viral hepatitides are common causes of liver diseases globally. Trials have assessed bile acids for patients with viral hepatitis, but no consensus was reached regarding their usefulness.......The viral hepatitides are common causes of liver diseases globally. Trials have assessed bile acids for patients with viral hepatitis, but no consensus was reached regarding their usefulness....

  16. Effects of Tip Clearance and Casing Recess on Heat Transfer and Stage Efficiency in Axial Turbines

    Science.gov (United States)

    Ameri, A. A.; Steinthorsson, E.; Rigby, David L.

    1998-01-01

    Calculations were performed to assess the effect of the tip leakage flow on the rate of heat transfer to blade, blade tip and casing. The effect on exit angle and efficiency was also examined. Passage geometries with and without casing recess were considered. The geometry and the flow conditions of the GE-E 3 first stage turbine, which represents a modem gas turbine blade were used for the analysis. Clearance heights of 0%, 1%, 1.5% and 3% of the passage height were considered. For the two largest clearance heights considered, different recess depths were studied. There was an increase in the thermal load on all the heat transfer surfaces considered due to enlargement of the clearance gap. Introduction of recessed casing resulted in a drop in the rate of heat transfer on the pressure side but the picture on the suction side was found to be more complex for the smaller tip clearance height considered. For the larger tip clearance height the effect of casing recess was an orderly reduction in the suction side heat transfer as the casing recess height was increased. There was a marked reduction of heat load and peak values on the blade tip upon introduction of casing recess, however only a small reduction was observed on the casing itself. It was reconfirmed that there is a linear relationship between the efficiency and the tip gap height. It was also observed that the recess casing has a small effect on the efficiency but can have a moderating effect on the flow underturning at smaller tip clearances.

  17. 75 FR 38959 - Lead; Clearance and Clearance Testing Requirements for the Renovation, Repair, and Painting...

    Science.gov (United States)

    2010-07-07

    ... From the Federal Register Online via the Government Publishing Office ENVIRONMENTAL PROTECTION AGENCY 40 CFR Part 745 RIN 2070-AJ57 Lead; Clearance and Clearance Testing Requirements for the Renovation, Repair, and Painting Program; Reopening of Comment Period AGENCY: Environmental Protection...

  18. Multiplex RT Q-PCR assay for simultaneous quantification of three viruses used for validation of virus clearance by biopharmaceutical production.

    Science.gov (United States)

    Lute, Scott; Wang, Hua; Sanchez, Davonie; Barletta, Janet; Chen, Qi; Brorson, Kurt

    2009-10-01

    Virus removal studies are used to insure the safety of biopharmaceutical products by quantitatively estimating the viral clearance capacity by the manufacturing process. Virus quantification assays are used to measure the log(10) clearance factor of individual purification unit operations in spike recovery studies. We have developed a multiplex RT Q-PCR assay that detects and quantifies three commonly used model viruses X-MuLV, SV40, and MMV simultaneously. This RT Q-PCR multiplex assay has a 6log(10) dynamic range with a limit of detection (LOD) of approximately 1 genome copy/microL. Amplification profiles are similar to existing singleplex assays. Overall, this RT Q-PCR multiplex assay is highly quantitative, accurately identifies multiple viruses simultaneously, and may prove useful to validate viral clearance of biological products in small scale studies.

  19. Viral Inhibition of PRR-Mediated Innate Immune Response: Learning from KSHV Evasion Strategies.

    Science.gov (United States)

    Lee, Hye-Ra; Choi, Un Yung; Hwang, Sung-Woo; Kim, Stephanie; Jung, Jae U

    2016-11-30

    The innate immune system has evolved to detect and destroy invading pathogens before they can establish systemic infection. To successfully eradicate pathogens, including viruses, host innate immunity is activated through diverse pattern recognition receptors (PRRs) which detect conserved viral signatures and trigger the production of type I interferon (IFN) and pro-inflammatory cytokines to mediate viral clearance. Viral persistence requires that viruses co-opt cellular pathways and activities for their benefit. In particular, due to the potent antiviral activities of IFN and cytokines, viruses have developed various strategies to meticulously modulate intracellular innate immune sensing mechanisms to facilitate efficient viral replication and persistence. In this review, we highlight recent advances in the study of viral immune evasion strategies with a specific focus on how Kaposi's sarcoma-associated herpesvirus (KSHV) effectively targets host PRR signaling pathways.

  20. Predicting Clearance Mechanism in Drug Discovery: Extended Clearance Classification System (ECCS).

    Science.gov (United States)

    Varma, Manthena V; Steyn, Stefanus J; Allerton, Charlotte; El-Kattan, Ayman F

    2015-12-01

    Early prediction of clearance mechanisms allows for the rapid progression of drug discovery and development programs, and facilitates risk assessment of the pharmacokinetic variability associated with drug interactions and pharmacogenomics. Here we propose a scientific framework--Extended Clearance Classification System (ECCS)--which can be used to predict the predominant clearance mechanism (rate-determining process) based on physicochemical properties and passive membrane permeability. Compounds are classified as: Class 1A--metabolism as primary systemic clearance mechanism (high permeability acids/zwitterions with molecular weight (MW) ≤400 Da), Class 1B--transporter-mediated hepatic uptake as primary systemic clearance mechanism (high permeability acids/zwitterions with MW >400 Da), Class 2--metabolism as primary clearance mechanism (high permeability bases/neutrals), Class 3A--renal clearance (low permeability acids/zwitterions with MW ≤400 Da), Class 3B--transporter mediated hepatic uptake or renal clearance (low permeability acids/zwitterions with MW >400 Da), and Class 4--renal clearance (low permeability bases/neutrals). The performance of the ECCS framework was validated using 307 compounds with single clearance mechanism contributing to ≥70% of systemic clearance. The apparent permeability across clonal cell line of Madin - Darby canine kidney cells, selected for low endogenous efflux transporter expression, with a cut-off of 5 × 10(-6) cm/s was used for permeability classification, and the ionization (at pH7) was assigned based on calculated pKa. The proposed scheme correctly predicted the rate-determining clearance mechanism to be either metabolism, hepatic uptake or renal for ~92% of total compounds. We discuss the general characteristics of each ECCS class, as well as compare and contrast the framework with the biopharmaceutics classification system (BCS) and the biopharmaceutics drug disposition classification system (BDDCS

  1. Unsteady Tip Clearance Flow in an Isolated Axial Compressor Rotor

    Institute of Scientific and Technical Information of China (English)

    Hongwu ZHANG; Xiangyang DENG; Jingyi CHEN; Weiguang HUANG

    2005-01-01

    The paper investigates effects of operating conditions, tip clearance sizes and external unsteady excitations on the unsteady tip clearance flow in an isolated axial compressor rotor by unsteady 3D Navier-Stokes simulations. The results show that the unsteady tip clearance vortex takes a periodic flow behavior in the rotor tip region. With the decrease of the flow coefficient, the unsteady tip clearance vortex is enhanced and its frequency becomes lower. A larger tip clearance size can cause bigger unsteady fluctuation amplitude and a lower fluctuation frequency of the tip clearance vortex at the near stall operating condition. The unsteady excitation with the natural frequency of the tip clearance vortex can enhance the unsteadiness of the tip clearance vortex and improve the overall rotor performance. The frequency of the unsteady tip clearance vortex is independent of external unsteady excitations with different frequencies.

  2. Viral infections in pigeons.

    Science.gov (United States)

    Marlier, D; Vindevogel, H

    2006-07-01

    This review provides a current update on the major viral diseases of the domestic pigeon (Columba livia domestica), based on scientific reports and clinical experience. Paramyxovirus 1, adenovirus, rotavirus, herpesvirus 1, poxvirus and circovirus infections are described according to common clinical signs and target tissues. Since pigeons are sometimes treated as if they were poultry, the review also summarises the common viral infections of poultry for which pigeons are considered resistant. It is hoped that the review will provide a useful reference for veterinarians and others and offer advice on the diagnosis, treatment and prevention of the major infectious diseases of pigeons.

  3. Viral meningitis and encephalitis.

    Science.gov (United States)

    Tuppeny, Misti

    2013-09-01

    Meningitis is an inflammation of the meninges, whereas encephalitis is inflammation of the parenchymal brain tissue. The single distinguishing element between the 2 diagnoses is the altered state of consciousness, focal deficits, and seizures found in encephalitis. Consequently meningoencephalitis is a term used when both findings are present in the patient. Viral meningitis is not necessarily reported as it is often underdiagnosed, whereas encephalitis cases are on the increase in various areas of North America. Improved imaging and viral diagnostics, as well as enhanced neurocritical care management, have improved patient outcomes to date.

  4. Container scanning to reduce time of customs clearance process

    Directory of Open Access Journals (Sweden)

    Yuri da Cunha Ferreira,

    2015-12-01

    Full Text Available One way to increase customs clearance efficiency and to assure supply chain security is the use of non-intrusive inspection equipment, such as scanners. In Brazil, scanners are new, but their use at port terminals is growing rapidly. Considering the possibility of Brazilian Customs requesting 100% scanning of loads, this study aims to assess the operational impacts of this possible request at a specific port terminal. This is the originality of this research. To do so, this study uses applied simulation methods in a case study. Results show that for the current scenario, scanners do not appear to be an operational bottleneck at this port, but the scanning capacity will be exceeded with the planned port expansion. Hence, scheduling rules for single machines were applied to optimize scanning performance. These heuristics provided good performance, suggesting that scanners can provide benefits to priority cargo handling, and could eventually increase the performance of port terminals throughout the country.

  5. Pharmacologic agents for mucus clearance in bronchiectasis.

    Science.gov (United States)

    Nair, Girish B; Ilowite, Jonathan S

    2012-06-01

    There are no approved pharmacologic agents to enhance mucus clearance in non-cystic fibrosis (CF) bronchiectasis. Evidence supports the use of hyperosmolar agents in CF, and studies with inhaled mannitol and hypertonic saline are ongoing in bronchiectasis. N-acetylcysteine may act more as an antioxidant than a mucolytic in other lung diseases. Dornase α is beneficial to patients with CF, but is not useful in patients with non-CF bronchiectasis. Mucokinetic agents such as β-agonists have the potential to improve mucociliary clearance in normals and many disease states, but have not been adequately studied in patients with bronchiectasis.

  6. Clinical evaluation of amylase-creatinine clearance ratio and amylase isoenzyme clearance in chronic renal failure.

    Science.gov (United States)

    Maeda, M; Otsuki, M; Okano, K; Yamasaki, T; Baba, S

    1981-01-01

    Amylase-creatinine clearance ratio (ACCR) and amylase isoenzyme clearance were determined simultaneously in patients with chronic renal failure. ACCR in patients with compensated renal failure (3.5 +/- 0.4%) was not significantly different from normals (2.6 +/- 0.2%), while that in patients with non-compensated renal failure (6.7 +/- 0.4%) was significantly higher than that in normals. Clearance ratio of pancreatic isoamylase (Amylase-1) relative to creatinine clearance (CAmy . 1/Ccr) in patients with both compensated (5.9 +/- 1.0%) and non-compensated (6.8 +/- 0.4%) renal failure was as high as that in patients with acute pancreatitis (6.6 +/- 0.5%). On the other hand, clearance ratio of salivary isoamylase (Amylase-3) relative to creatinine clearance (CAmy . 3/CCr) in patients with compensated renal failure (1.5 +/- 0.3%) was almost the same as that in normals (2.1 +/- 0.1%), while that in patients with non-compensated renal failure was 5.9 +/- 0.7%, which was significantly higher than that in normals. The present study revealed that elevated ACCR in patients with severely impaired renal function was due to the increase of the clearance ratio for both pancreatic and salivary amylase. These facts suggested that glomerular permeability and tubular reabsorption for pancreatic and salivary amylase might play an important role on ACCR in patients with severely impaired renal function.

  7. Cystine accumulation and clearance by normal and cystinotic leukocytes exposed to cystine dimethyl ester.

    OpenAIRE

    Steinherz, R; Tietze, F.; Gahl, W A; Triche, T J; Chiang, H.; Modesti, A.; Schulman, J D

    1982-01-01

    Upon exposure to 0.25 mM cystine dimethyl ester, normal and cystinotic leukocytes accumulate substantially more intracellular cystine than is present endogenously in cystinotic cells. Leukocytes loaded by exposure to cystine dimethyl ester may have abnormally lucent and distended lysosomes, and the cystine is compartmentalized within the granular fraction of the cells. After the cells are exposed to cystine dimethyl ester, cystine clearance from normal leukocytes is much faster than from cyst...

  8. The correlation study of HBoV viral load and disease severity in children with lower respiratory tract infections%儿童下呼吸道人类博卡病毒感染的病毒载量和疾病严重程度相关性研究

    Institute of Scientific and Technical Information of China (English)

    赵百慧; 王春; 滕峥; 沈佳仁; 高烨; 俞雪莲; 张泓; 张曦

    2013-01-01

    Objective To study the correlation of human bocavirus (HBoV)viral load and disease severity in children with lower respiratory tract infections.Methods Nasopharyngeal aspirates (NPAs ) from 554 in-hospital children with lower respiratory tract infections under 5-year-old and swabs from 1 95 healthy children were collected from January 2009 to September 201 2.The types of HBoV and HBoV viral load were determined by fluorescence polymerase chain reaction (PCR).The other respiratory viruses were determined by commercial kits.The results were analyzed with clinical symptoms and biochemistry parameters.Results The positive rates of HBoV between in-hospital children and healthy children had obvious difference.The HBoV viral loads of in-hospital children (5.1 0 ×1 06 copies/mL)were significantly higher than those of healthy children (2.70 ×1 03 copies/mL,P<0.05 ).Among co-infection in-hospital children,the HBoV viral loads of mild and moderate groups (2.70 ×1 05 and 3.85 ×1 06 copies/mL)were lower than that in severe group (8.70 ×1 06 copies/mL,P<0.05 ).There was 1 case of newborn infant with severe pneumonia, and HBoV were found in NPAs,blood and stool samples without other common respiratory trract virus and bacterium infections.Conclusions HBoV is a pathogen for respiratory tract disease in children.HBoV viral load is correlated positively with disease severity in co-infection patients.HBoV can cause severe pneumonia in some children.%目的:研究下呼吸道感染患儿人类博卡病毒(HBoV)载量与疾病严重程度的相关性。方法对2009年1月至2012年9月间554例因下呼吸道感染住院的5岁以下患儿及195名健康对照组儿童下呼吸道吸出物(NPAs)、鼻咽拭子采用荧光聚合酶链反应(PCR)检测HBoV种类,并同时测定阳性标本感染HBoV的载量,利用商品化试剂盒检测其他种类的呼吸道病毒,结合患儿的临床症状和生化指标进行综合分析。结果实验组与健康对照

  9. 14 CFR 23.925 - Propeller clearance.

    Science.gov (United States)

    2010-01-01

    ... seven inches (for each airplane with nose wheel landing gear) or nine inches (for each airplane with tail wheel landing gear) between each propeller and the ground with the landing gear statically.... Positive clearance for airplanes using leaf spring struts is shown with a deflection corresponding to...

  10. Bile acids for viral hepatitis

    DEFF Research Database (Denmark)

    Chen, Weikeng; Liu, J; Gluud, C

    2007-01-01

    Trials have assessed bile acids for patients with viral hepatitis, but no consensus has been reached regarding their usefulness.......Trials have assessed bile acids for patients with viral hepatitis, but no consensus has been reached regarding their usefulness....

  11. Dynamics modeling and simulation of mechanism with joint clearance

    Institute of Scientific and Technical Information of China (English)

    BAI Zheng-feng; TIAN Hao; ZHAO Yang

    2010-01-01

    The existence of clearance in the joints of mechanisms system is inevitable.The movements of the real mechanism are deftection from the ideal mechanism due to the clearances and the motion accuracv is decreased.The effects of the hinge clearance on the crank and rocker mechanism system are studied.The svstem dynamics equation with clearance is presented.The contact dynamics model is established using the nonlinear equivalent spring-damp model and the friction effect is considered by using Coulomb friction model.Then the models are incorporated into ADAMS,and based on the model,large numbers numeric simulations are made.The regularity of contact forces in clearance are studied in detail.And the effects of clearance size.clearance friction on the mechanism dynamics characteristic are analyzed.The simulation resuhs Can predict the effects of clearance on the mechanism dynamics characteristic preferably.

  12. Distinguishing aggregate formation and aggregate clearance using cell based assays

    NARCIS (Netherlands)

    E. Eenjes, E.; J.M. Dragich; H. Kampinga (Harm); A. Yamamoto, A.

    2016-01-01

    textabstractThe accumulation of ubiquitinated proteinaceous inclusions represents a complex process, reflecting the disequilibrium between aggregate formation and aggregate clearance. Although decreasing aggregate formation or augmenting aggregate clearance will ultimately lead to diminished aggrega

  13. 19 CFR 122.26 - Entry and clearance.

    Science.gov (United States)

    2010-04-01

    ... AIR COMMERCE REGULATIONS Private Aircraft § 122.26 Entry and clearance. Private aircraft, as defined... information as set forth in § 122.22(c), and grants electronic clearance via electronic mail or telephone....

  14. Viral Marketing and Academic Institution

    OpenAIRE

    Koktová, Silvie

    2010-01-01

    This bachelor thesis examines modern and constantly developing kind of internet marketing -- the so called viral marketing. It deals with its origin, principle, process, advantages and disadvantages, types of viral marketing and presumptions of creating successful viral campaign. The aim of the theoretical part is especially the understanding of viral marketing as one of the effective instruments of contemporary marketing. In this theoretical part the thesis also elaborates a marketing school...

  15. Relevance research of viral load and peripheral T lymphocyte subset in patients with HIV and HBV coinfection%HIV、HBV共感染患者病毒载量和外周T淋巴细胞亚群的相关性研究

    Institute of Scientific and Technical Information of China (English)

    郑立娜; 金明珠

    2015-01-01

    Objective To investigate the correlation between viral load and peripheral T lymphocyte subset in patients with HIV and HBV coinfection. Methods From January 2011 to January 2014 in Yueqing Blood Supply Center of Out-patient and Inpatient Department, 1230 cases of untreated HIV infected patients with highly active antiretroviral thera-py were selected as simple infection group, 148 patients with HIV and HBV coinfection were selected as coinfection group. RT-PCR, fluorescent quantitative PCR and flow cytometry were adopted to detect the HIV and HBC viral load and T lymphocyte subsets count. Fully automatic biochemical analyzer was adopted to detect related biochemical index. The detection results between two groups were compared. The correlations between viral load and T lymphocyte subsets count in HIV and HBV coinfection patients were analyzed. Results ALT, AST, TP, ALB, TBIL level and HIV RNA load between two groups was compared respectively, there were significantly statistical differences (P< 0.01). CD4+, CD8+, CD3+T lymphocyte subsets count and CD4+/CD8+was compared respectively, there were significantly statistical differences (P<0.01).There was a positive correlation of HIV RNA load and HBV DNA load in coinfection patients (r=0.471). CD4+/CD8+was negatively correlate with HBV DNA load (r=-0.412). CD4+, CD4+/CD8+were negatively corre-late with HIV RNA load (r =-0.841,-0.583). Conclusion HBV may has promoting HIV RNA replication effect which makes a worse liver damage and immune system damage in coinfection patients than HIV infection along patients, should pay attention to in clinic.%目的:研究HIV、HBV共感染患者病毒载量与外周T淋巴细胞亚群的相关性。方法选取2011年1月~2014年1月就诊于乐清市血站门诊和住院部未经高效抗逆转录病毒治疗的HIV感染患者1230例为单纯感染组和HIV、HBV共感染患者148例为共感染组。采用RT-PCR、荧光定量PCR和流式细胞仪进行HIV、HBV病毒载量和T

  16. Modelling Virus and Antibody Dynamics during Dengue Virus Infection Suggests a Role for Antibody in Virus Clearance.

    Directory of Open Access Journals (Sweden)

    Hannah E Clapham

    2016-05-01

    Full Text Available Dengue is an infection of increasing global importance, yet uncertainty remains regarding critical aspects of its virology, immunology and epidemiology. One unanswered question is how infection is controlled and cleared during a dengue infection. Antibody is thought to play a role, but little past work has examined the kinetics of both virus and antibody during natural infections. We present data on multiple virus and antibody titres measurements recorded sequentially during infection from 53 Vietnamese dengue patients. We fit mechanistic mathematical models of the dynamics of viral replication and the host immune response to these data. These models fit the data well. The model with antibody removing virus fits the data best, but with a role suggested for ADCC or other infected cell clearance mechanisms. Our analysis therefore shows that the observed viral and antibody kinetics are consistent with antibody playing a key role in controlling viral replication. This work gives quantitative insight into the relationship between antibody levels and the efficiency of viral clearance. It will inform the future development of mechanistic models of how vaccines and antivirals might modify the course of natural dengue infection.

  17. Diminished creatinine clearance in anorexia nervosa: reversal with weight gain.

    OpenAIRE

    Boag, F; Weerakoon, J; Ginsburg, J.; Havard, C W; Dandona, P

    1985-01-01

    To assess whether patients with anorexia nervosa have abnormalities in creatinine clearance, we measured plasma creatinine concentration, urinary creatinine excretion, and creatinine clearance in 10 patients with anorexia nervosa before and during treatment. Urinary creatinine excretion and creatinine clearance were diminished in all patients. Nine patients had significant decreases in their plasma creatinine and creatinine clearance was increased even when corrected for body weight and body ...

  18. Increased T-cell responses to Epstein-Barr virus with high viral load in patients with Epstein-Barr virus-positive diffuse large B-cell lymphoma.

    Science.gov (United States)

    Morishima, Satoko; Nakamura, Shigeo; Yamamoto, Kazuhito; Miyauchi, Hidemasa; Kagami, Yoshitoyo; Kinoshita, Tomohiro; Onoda, Hiroshi; Yatabe, Yasushi; Ito, Masafumi; Miyamura, Kouichi; Nagai, Hirokazu; Moritani, Suzuko; Sugiura, Isamu; Tsushita, Keitaro; Mihara, Hidetsugu; Ohbayashi, Kaneyuki; Iba, Sachiko; Emi, Nobuhiko; Okamoto, Masataka; Iwata, Seiko; Kimura, Hiroshi; Kuzushima, Kiyotaka; Morishima, Yasuo

    2015-04-01

    The immunological status of patients with Epstein-Barr virus-positive diffuse large B-cell lymphoma (EBV+ DLBCL) without obvious immunodeficiency has not been elucidated. A multicenter prospective study was conducted to assess pretreatment T-cell responses to EBV, EBV-DNA load and anti-EBV antibody in these patients. The proliferative and interferon (IFN)-γ-producing capacity of T-cells in response to autologous B-lymphoblastoid cell lines was determined using carboxyfluorescein diacetate succinimidyl ester (CFSE)-based assay. Frequencies of EBV-specific CD4+ T-cells in patients with EBV+ DLBCL (n = 13) were significantly higher than in healthy controls (HCs) (n = 16) after both ex vivo and in vitro stimulation. Frequencies of EBV-specific CD8+ T-cells in patients with EBV+ DLBCL tended to be higher than in HCs after in vitro stimulation. Patients with EBV+ DLBCL also showed increased immunoglobulin G (IgG) responses to lytic EBV-encoded antigens. Pretreatment plasma EBV-DNA level was significantly higher in patients with EBV+ DLBCL than in patients with EBV- DLBCL or HCs. In conclusion, EBV-specific T-cells showed increased reactivity, accompanied by higher levels of plasma virus DNA in patients with EBV+ DLBCL.

  19. Curative efficacy of short-haul methylprednisolone pulse therapy loaded with interferon in the treatment of pe-diatric viral encephalitis%短程甲基强的松冲击疗法加干扰素治疗小儿病毒性脑炎

    Institute of Scientific and Technical Information of China (English)

    梁跃波; 冉敏; 蒲向阳

    2015-01-01

    Objective To observe the effect of short methylprednisolone pulse therapy combined with interferon in the treatment of pediatric viral encephalitis .Methods 34 cases of children with viral encephalitis were selected and were randomly divided into two groups:the control group(n=15) and the observation group(n=19) .The control group was treated with in‐terferon treatment ,and the observation group was treated with methylprednisolone pulse therapy loaded with interferon treat‐ment .The time of the clinical symptoms improvement and differences of efficacy between the two groups were compared .Re‐sults The time of fever ,convulsions ,meningeal irritation (Kernig sign ,Brudzinski sign) ,pathologic reflex(Babinski sign) , unconsciousness ,the recovery of intracranial hypertension were significantly shorter than the control group (P<0 .05) .The total efficiency rate in the observation group was up to 94 .74% ,which was significantly higher than 60 .00% of the control group ,and the inefficiency rate was significantly lower than the control group (P<0 .05) .Conclusion On the basis of inter‐feron treatment ,loaded with short methylprednisolone pulse therapy can effectively reduce the time of the clinical symptoms improvement and efficacy .%目的:观察短程甲基强的松冲击疗法加干扰素治疗小儿病毒性脑炎的疗效。方法收集小儿病毒性脑炎患儿34例,随机分对照组15例和观察组19例。对照组采用干扰素治疗,观察组采用短程甲基强的松冲击疗法加干扰素治疗。比较2组患儿临床症状改善时间及疗效。结果观察组发热、抽搐、脑膜刺激征、病理征、意识障碍、颅内高压的恢复时间均显著短于对照组(P<0.05)。观察组总有效率94.74%,显著高于对照组的60.00%(P<0.05)。结论短程甲基强的松冲击疗法加干扰素治疗小儿病毒性脑炎能有效缩短临床症状改善时间并提高疗效。

  20. 10 CFR 706.31 - Clearance of conciliators and arbitrators.

    Science.gov (United States)

    2010-01-01

    ... 10 Energy 4 2010-01-01 2010-01-01 false Clearance of conciliators and arbitrators. 706.31 Section... RELATIONS Contract Negotiation and Administration § 706.31 Clearance of conciliators and arbitrators. Conciliators and arbitrators who are regularly assigned to DOE cases may be processed for “Q” clearance at...

  1. 33 CFR 151.1508 - Revocation of clearance.

    Science.gov (United States)

    2010-07-01

    ... 33 Navigation and Navigable Waters 2 2010-07-01 2010-07-01 false Revocation of clearance. 151.1508... River § 151.1508 Revocation of clearance. A COTP may request the District Director of Customs to withhold or revoke the clearance required by 46 U.S.C. app. 91 for a vessel subject to this subpart,...

  2. 49 CFR Appendix F to Part 512 - OMB Clearance

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 6 2010-10-01 2010-10-01 false OMB Clearance F Appendix F to Part 512 Transportation Other Regulations Relating to Transportation (Continued) NATIONAL HIGHWAY TRAFFIC SAFETY... 512—OMB Clearance The OMB clearance number for this part 512 is 2127-0025....

  3. 10 CFR 95.17 - Processing facility clearance.

    Science.gov (United States)

    2010-01-01

    ... 10 Energy 2 2010-01-01 2010-01-01 false Processing facility clearance. 95.17 Section 95.17 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) FACILITY SECURITY CLEARANCE AND SAFEGUARDING OF NATIONAL SECURITY INFORMATION AND RESTRICTED DATA Physical Security § 95.17 Processing facility clearance....

  4. 48 CFR 952.204-73 - Facility clearance.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Facility clearance. 952... clearance. As prescribed in 904.404(d)(5), insert the following provision in all solicitations which require... subcontracts subject to the provisions of 904.70: Facility Clearance (MAY 2002) Notices Section 2536 of...

  5. 14 CFR 27.661 - Rotor blade clearance.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Rotor blade clearance. 27.661 Section 27.661 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION AIRCRAFT... clearance. There must be enough clearance between the rotor blades and other parts of the structure...

  6. 50 CFR 14.53 - Detention and refusal of clearance.

    Science.gov (United States)

    2010-10-01

    ... 50 Wildlife and Fisheries 1 2010-10-01 2010-10-01 false Detention and refusal of clearance. 14.53... PLANTS IMPORTATION, EXPORTATION, AND TRANSPORTATION OF WILDLIFE Inspection and Clearance of Wildlife § 14.53 Detention and refusal of clearance. (a) Detention. Any Service officer, or Customs officer...

  7. 23 CFR Appendix B to Part 1327 - OMB Clearance

    Science.gov (United States)

    2010-04-01

    ... 23 Highways 1 2010-04-01 2010-04-01 false OMB Clearance B Appendix B to Part 1327 Highways NATIONAL HIGHWAY TRAFFIC SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION PROCEDURES FOR PARTICIPATING..., App. B Appendix B to Part 1327—OMB Clearance The OMB clearance number of this regulation is OMB...

  8. 8 CFR 280.6 - Bond to obtain clearance; form.

    Science.gov (United States)

    2010-01-01

    ... 8 Aliens and Nationality 1 2010-01-01 2010-01-01 false Bond to obtain clearance; form. 280.6 Section 280.6 Aliens and Nationality DEPARTMENT OF HOMELAND SECURITY IMMIGRATION REGULATIONS IMPOSITION AND COLLECTION OF FINES § 280.6 Bond to obtain clearance; form. A bond to obtain clearance of a...

  9. 10 CFR 95.23 - Termination of facility clearance.

    Science.gov (United States)

    2010-01-01

    ... 10 Energy 2 2010-01-01 2010-01-01 false Termination of facility clearance. 95.23 Section 95.23 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) FACILITY SECURITY CLEARANCE AND SAFEGUARDING OF NATIONAL SECURITY INFORMATION AND RESTRICTED DATA Physical Security § 95.23 Termination of facility clearance....

  10. 32 CFR 644.527 - Recording Statements of Clearance.

    Science.gov (United States)

    2010-07-01

    ... 32 National Defense 4 2010-07-01 2010-07-01 true Recording Statements of Clearance. 644.527... PROPERTY REAL ESTATE HANDBOOK Disposal Clearance of Explosive Hazards and Other Contamination from Proposed Excess Land and Improvements § 644.527 Recording Statements of Clearance. On property disposals for...

  11. 14 CFR 29.661 - Rotor blade clearance.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Rotor blade clearance. 29.661 Section 29.661 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION AIRCRAFT... clearance. There must be enough clearance between the rotor blades and other parts of the structure...

  12. 46 CFR 56.75-10 - Joint clearance.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 2 2010-10-01 2010-10-01 false Joint clearance. 56.75-10 Section 56.75-10 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING PIPING SYSTEMS AND APPURTENANCES Brazing § 56.75-10 Joint clearance. (a) The clearance between surfaces to be joined shall be...

  13. 19 CFR 122.157 - Documents required for clearance.

    Science.gov (United States)

    2010-04-01

    ... 19 Customs Duties 1 2010-04-01 2010-04-01 false Documents required for clearance. 122.157 Section 122.157 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT... clearance. As a condition precedent to clearance, the aircraft commander shall present to Customs: (a)...

  14. 33 CFR 157.455 - Minimum under-keel clearance.

    Science.gov (United States)

    2010-07-01

    ... 33 Navigation and Navigable Waters 2 2010-07-01 2010-07-01 false Minimum under-keel clearance. 157... § 157.455 Minimum under-keel clearance. (a) The owner or operator of a tankship, that is not fitted with... written under-keel clearance guidance that includes— (1) Factors to consider when calculating the...

  15. 8 CFR 1280.6 - Bond to obtain clearance; form.

    Science.gov (United States)

    2010-01-01

    ... 8 Aliens and Nationality 1 2010-01-01 2010-01-01 false Bond to obtain clearance; form. 1280.6... IMMIGRATION REGULATIONS IMPOSITION AND COLLECTION OF FINES § 1280.6 Bond to obtain clearance; form. A bond to obtain clearance of a vessel or aircraft under section 231, 237, 239, 243, 251, 253, 254, 255, 256,...

  16. 76 FR 17615 - Highway-Rail Grade Crossing; Safe Clearance

    Science.gov (United States)

    2011-03-30

    ... Parts 177 and 392 RIN 2137-AE69 & 2126-AB04 Highway-Rail Grade Crossing; Safe Clearance AGENCY: Pipeline... that PHMSA and FMCSA extend the comment period for the Highway-Rail Grade Crossing; Safe Clearance... Crossing; Safe Clearance Notice of Proposed Rulemaking, which was published on January 28, 2011 (76 FR...

  17. 14 CFR 375.24 - Entry and clearance.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 4 2010-01-01 2010-01-01 false Entry and clearance. 375.24 Section 375.24 Aeronautics and Space OFFICE OF THE SECRETARY, DEPARTMENT OF TRANSPORTATION (AVIATION PROCEEDINGS) SPECIAL... Entry and clearance. All U.S. entry and clearance requirements for aircraft, passengers, crews,...

  18. 32 CFR 644.521 - Limitations on clearance cost.

    Science.gov (United States)

    2010-07-01

    ... 32 National Defense 4 2010-07-01 2010-07-01 true Limitations on clearance cost. 644.521 Section... PROPERTY REAL ESTATE HANDBOOK Disposal Clearance of Explosive Hazards and Other Contamination from Proposed Excess Land and Improvements § 644.521 Limitations on clearance cost. The following principles...

  19. Guangzhou Customs Guide to Clearance of Import/Export Goods

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    @@ Management of the Enterprises Granted for Convenient and Quick Customs Clearance 1.What is the enterprise granted for convenient and quick customs clearance? Customs General Administration and the Ministry of Foreign Trade and Economic Cooperation jointly issued policy measures to facilitate customs clearance in 2001 to further support the development of hightech industries.The enterprise .

  20. 14 CFR 1260.63 - Customs clearance and visas.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 5 2010-01-01 2010-01-01 false Customs clearance and visas. 1260.63 Section 1260.63 Aeronautics and Space NATIONAL AERONAUTICS AND SPACE ADMINISTRATION GRANTS AND COOPERATIVE AGREEMENTS General Special Conditions § 1260.63 Customs clearance and visas. Customs Clearance and Visas...

  1. The influence of body posture on lithium clearance

    DEFF Research Database (Denmark)

    Kamper, A L; Strandgaard, S; Holstein-Rathlou, N H;

    1988-01-01

    To establish appropriate standard circumstances for lithium clearance measurements, a study was undertaken in 12 healthy volunteers. In each subject, the glomerular filtration rate (GFR), as estimated by [51Cr]EDTA plasma clearance, and the renal clearances of lithium, sodium and potassium were m...

  2. 32 CFR 644.517 - Clearance of Army lands.

    Science.gov (United States)

    2010-07-01

    ... 32 National Defense 4 2010-07-01 2010-07-01 true Clearance of Army lands. 644.517 Section 644.517 National Defense Department of Defense (Continued) DEPARTMENT OF THE ARMY (CONTINUED) REAL PROPERTY REAL... and Improvements § 644.517 Clearance of Army lands. The responsibility for performing clearance...

  3. Viral quasispecies evolution

    OpenAIRE

    Domingo, Esteban; Sheldon, Julie; Perales, Celia

    2012-01-01

    Summary: Evolution of RNA viruses occurs through disequilibria of collections of closely related mutant spectra or mutant clouds termed viral quasispecies. Here we review the origin of the quasispecies concept and some biological implications of quasispecies dynamics. Two main aspects are addressed: (i) mutant clouds as reservoirs of phenotypic variants for virus adaptability and (ii) the internal interactions that are established within mutant spectra that render a virus ensemble the unit of...

  4. Viral membrane fusion

    Energy Technology Data Exchange (ETDEWEB)

    Harrison, Stephen C., E-mail: harrison@crystal.harvard.edu

    2015-05-15

    Membrane fusion is an essential step when enveloped viruses enter cells. Lipid bilayer fusion requires catalysis to overcome a high kinetic barrier; viral fusion proteins are the agents that fulfill this catalytic function. Despite a variety of molecular architectures, these proteins facilitate fusion by essentially the same generic mechanism. Stimulated by a signal associated with arrival at the cell to be infected (e.g., receptor or co-receptor binding, proton binding in an endosome), they undergo a series of conformational changes. A hydrophobic segment (a “fusion loop” or “fusion peptide”) engages the target-cell membrane and collapse of the bridging intermediate thus formed draws the two membranes (virus and cell) together. We know of three structural classes for viral fusion proteins. Structures for both pre- and postfusion conformations of illustrate the beginning and end points of a process that can be probed by single-virion measurements of fusion kinetics. - Highlights: • Viral fusion proteins overcome the high energy barrier to lipid bilayer merger. • Different molecular structures but the same catalytic mechanism. • Review describes properties of three known fusion-protein structural classes. • Single-virion fusion experiments elucidate mechanism.

  5. COMPARISON OF TWO METHODS TO INCREASE TIP CLEARANCE AND ITS EFFECT ON PERFORMANCE OF TURBOCHARGER CENTRIFUGAL COMPRESSOR STAGE

    Institute of Scientific and Technical Information of China (English)

    SYED Noman Danish; MA Chaochen; YANG Ce; L(U) Wei

    2007-01-01

    Tip clearance between the blade tip and casing of a centrifugal compressor can be varied through two methods: by changing the blade height (M1) or by changing the casing diameter (M2). Numerical simulations are carried out to compare these two methods and their effect on the stage and impeller performance. The impeller and diffuser are connected through rotor Stator boundary using frozen rotor approach. Overall stage performance and the flow configuration have been investigated for nine tip clearance levels from no gap to 1 mm. Impeller and diffuser performances are also presented separately. It has been found that the overall and impeller performance are comparatively better for Ml below tip clearance of 0.5 mm whereas M2 is found advantageous above 0.5 mm of tip clearance. Both M1 and M2 show performance degradation with the increase in tip clearance. Two models have been proposed for the stage total pressure ratio and efficiency, which are found to be in agreement with experimental results. The impeller efficiency and the pressure ratio are found to be maximum at tip clearance of 0.1 mm for both the cases however minimum diffuser effectiveness is also observed at the same clearance level. Diffuser effectiveness is found to be maximum at zero gap for both cases. As it is practically impossible to have zero gap for unshrouded impellers so it is concluded that the Optimum thickness is 0.5 mm onwards for Ml and 0.5 mm for M2 in terms of diffuser effectiveness. Mass averaged flow parameters, entropy, blade loading diagram and relative pressure fields are presented, showing the loss production within the impeller passage with tip clearance.

  6. Non-cytolytic antigen clearance in DNA-vaccinated mice with electropotation

    Institute of Scientific and Technical Information of China (English)

    Jin-liang PENG; Yong-gang ZHAO; Jun-hua MAI; Wen-ka PANG; Wei GUO; Guang-ming CHEN; Guo-yu MO; Gui-rong RAO; Yu-hong XU

    2007-01-01

    Aim: To explore the potential of electroporation (EP)-mediated hepatitis B virus (HBV) DNA vaccination for the treatment of chronic HBV infection. Methods: BALB/c mice were vaccinated with HBV DNA vaccine encoding for the HBV preS2-S antigen, combined with or without EP. HBV surface antigen expression plasmid was administered into mice liver via a hydrodynamic injection to mimic HBV infection. The clearance of antigen in the serum and liver was detected by ELISA assay and immunohistochemical staining. The histopathology of the liver tissues was examined by HE staining and serum alanine aminotransferase assay.Results: The immunogenicity ofHBV DNA vaccine encoding for the HBV preS2-S antigen can be improved by EP-mediated vaccine delivery. The elicited immune responses can indeed reduce the expression of HBV surface antigen (HBsAg) in hepatocytes of the mouse model that was transfected to express HBsAg using the hydrodynamic injection method. The antigen clearance process did not cause significant toxicity to liver tissue, suggesting a non-cytolytic mechanism. Conclusion: The EP-aided DNA vaccination may have potential in mediating viral clearance in chronic hepatitis B patients.

  7. Early changes in hepatitis C viral quasispecies during interferon therapy predict the therapeutic outcome

    Science.gov (United States)

    Farci, Patrizia; Strazzera, Rita; Alter, Harvey J.; Farci, Stefania; Degioannis, Daniela; Coiana, Alessandra; Peddis, Giovanna; Usai, Francesco; Serra, Giancarlo; Chessa, Luchino; Diaz, Giacomo; Balestrieri, Angelo; Purcell, Robert H.

    2002-01-01

    Despite recent treatment advances, the majority of patients with chronic hepatitis C fail to respond to antiviral therapy. Although the genetic basis for this resistance is unknown, accumulated evidence suggests that changes in the heterogeneous viral population (quasispecies) may be an important determinant of viral persistence and response to therapy. Sequences within hepatitis C virus (HCV) envelope 1 and envelope 2 genes, inclusive of the hypervariable region 1, were analyzed in parallel with the level of viral replication in serial serum samples obtained from 23 patients who exhibited different patterns of response to therapy and from untreated controls. Our study provides evidence that although the viral diversity before treatment does not predict the response to treatment, the early emergence and dominance of a single viral variant distinguishes patients who will have a sustained therapeutic response from those who subsequently will experience a breakthrough or relapse. A dramatic reduction in genetic diversity leading to an increasingly homogeneous viral population was a consistent feature associated with viral clearance in sustained responders and was independent of HCV genotype. The persistence of variants present before treatment in patients who fail to respond or who experience a breakthrough during therapy strongly suggests the preexistence of viral strains with inherent resistance to IFN. Thus, the study of the evolution of the HCV quasispecies provides prognostic information as early as the first 2 weeks after starting therapy and opens perspectives for elucidating the mechanisms of treatment failure in chronic hepatitis C. PMID:11880647

  8. ABCA7 Mediates Phagocytic Clearance of Amyloid-β in the Brain.

    Science.gov (United States)

    Fu, YuHong; Hsiao, Jen-Hsiang T; Paxinos, George; Halliday, Glenda M; Kim, Woojin Scott

    2016-09-06

    Alzheimer's disease (AD) is a neurodegenerative disorder characterized by dementia and abnormal deposits of aggregated amyloid-β in the brain. Recent genome-wide association studies have revealed that ABCA7 is strongly associated with AD. In vitro evidence suggests that the role of ABCA7 is related to phagocytic activity. Deletion of ABCA7 in a mouse model of AD exacerbates cerebral amyloid-β plaque load. However, the biological role of ABCA7 in AD brain pathogenesis is unknown. We show that ABCA7 is highly expressed in microglia and when monocytes are differentiated into macrophages. We hypothesized that ABCA7 plays a protective role in the brain that is related to phagocytic clearance of amyloid-β. We isolated microglia and macrophages from Abca7-/- and wild type mice and tested them for their capacity to phagocytose amyloid-β oligomers. We found that the phagocytic clearance of amyloid-β was substantially reduced in both microglia and macrophages from Abca7-/- mice compared to wild type mice. Consistent with these results, in vivo phagocytic clearance of amyloid-β oligomers in the hippocampus was reduced in Abca7-/- mice. Furthermore, ABCA7 transcription was upregulated in AD brains and in amyloidogenic mouse brains specifically in the hippocampus as a response to the amyloid-β pathogenic state. Together these results indicate that ABCA7 mediates phagocytic clearance of amyloid-β in the brain, and reveal a mechanism by which loss of function of ABCA7 increases the susceptibility to AD.

  9. Progress on Shape Memory Alloy Actuator Development for Active Clearance Control

    Science.gov (United States)

    DeCastro, Jonathan; Melcher, Kevin; Noebe, Ronald

    2006-01-01

    Results of a numerical analysis evaluating the feasibility of high-temperature shape memory alloys (HTSMA) for active clearance control actuation in the high-pressure turbine section of a modern turbofan engine has been conducted. The prototype actuator concept considered here consists of parallel HTSMA wires attached to the shroud that is located on the exterior of the turbine case. A transient model of an HTSMA actuator was used to evaluate active clearance control at various operating points in a test bed aircraft engine simulation. For the engine under consideration, each actuator must be designed to counteract loads from 380 to 2000 lbf and displace at least 0.033 in. Design results show that an actuator comprised of 10 wires 2 in. in length is adequate for control at critical engine operating points and still exhibit acceptable failsafe operability and cycle life. A proportional-integral-derivative (PID) controller with integrator windup protection was implemented to control clearance amidst engine transients during a normal mission. Simulation results show that the control system exhibits minimal variability in clearance control performance across the operating envelope. The final actuator design is sufficiently small to fit within the limited space outside the high-pressure turbine case and is shown to consume only small amounts of bleed air to adequately regulate temperature.

  10. Hormonal regulation of glucose clearance in lactating northern elephant seals (Mirounga angustirostris).

    Science.gov (United States)

    Fowler, Melinda A; Champagne, Cory D; Houser, Dorian S; Crocker, Daniel E

    2008-09-01

    Northern elephant seals exhibit the rare strategy of fasting and lactating concomitantly. We investigated hormonal regulation of glucose clearance in northern elephant seals using glucose tolerance tests (GTT) performed early in lactation and again just prior to weaning. For comparison, identical measurements were made on separate females late in the molt fast. Serial blood samples were used to assess glucose clearance and hormone responses for 3 h post glucose injection. Plasma glucose remained elevated at the end of the sampling period in all groups. Glucose clearance rates were not significantly different among test groups. A significant insulin response was observed in early lactation, no significant response was observed late in lactation and an intermediate response was observed late in the molt fast. The insulin response to a glucose load decreased with adipose tissue proportions. Plasma glucagon decreased significantly following GTT in early and late lactation, although the magnitude of the depression was small in comparison to other species. Hypoinsulemia may be critical to facilitate net lipolysis late in lactation. Consistently low glucose clearance among test groups suggests insulin insensitivity within peripheral tissues. Glucagon suppression independent of insulin release suggests modification of the typical insulin-glucagon counter-regulation. These findings suggest that metabolic features of diabetic-like conditions may be adaptive in the context of long-term fasting.

  11. ADSORBENTS USED IN THE CLEARANCE OF ENDOTOXIN

    Institute of Scientific and Technical Information of China (English)

    YU Mei; LIU Tao; Hou Guanghui; YUAN Zhi

    2003-01-01

    A series of modified poly (methyl methacrylate, PMMA) resins were prepared and compared their adsorption abilities to endotoxin. The results showed that adsorbents, which were grafted with tertiary amine and long spacing arms, had the best adsorption capacities and good blood compatibility, It is hopeful to be used as adsorbent in hemoperfusion for clinical clearance of endotoxin. The influence of original concentration of endotoxin on adsorption and the adsorption mechanism were also investigated.

  12. Environmental modulation of mucosal immunity : Opportunities in respiratory viral infections

    NARCIS (Netherlands)

    Schijf, M.A.

    2013-01-01

    The exact cause of severe disease in children during primary RSV infections is not completely clear. There is a link with viral load, but differences virus strains do not seem to be the major reason why in some children the disease manifests as a mild cold while others suffer from a severe lower res

  13. Loss of CARD9-mediated innate activation attenuates severe influenza pneumonia without compromising host viral immunity.

    Science.gov (United States)

    Uematsu, Takayuki; Iizasa, Ei'ichi; Kobayashi, Noritada; Yoshida, Hiroki; Hara, Hiromitsu

    2015-12-02

    Influenza virus (IFV) infection is a common cause of severe viral pneumonia associated with acute respiratory distress syndrome (ARDS), which is difficult to control with general immunosuppressive therapy including corticosteroids due to the unfavorable effect on viral replication. Studies have suggested that the excessive activation of the innate immunity by IFV is responsible for severe pathologies. In this study, we focused on CARD9, a signaling adaptor known to regulate innate immune activation through multiple innate sensor proteins, and investigated its role in anti-IFV defense and lung pathogenesis in a mouse model recapitulating severe influenza pneumonia with ARDS. We found that influenza pneumonia was dramatically attenuated in Card9-deficient mice, which showed improved mortality with reduced inflammatory cytokines and chemokines in the infected lungs. However, viral clearance, type-I interferon production, and the development of anti-viral B and T cell immunity were not compromised by CARD9 deficiency. Syk or CARD9-deficient DCs but not macrophages showed impaired cytokine but not type-I interferon production in response to IFV in vitro, indicating a possible role for the Syk-CARD9 pathway in DCs in excessive inflammation of IFV-infected lungs. Therefore, inhibition of this pathway is an ideal therapeutic target for severe influenza pneumonia without affecting viral clearance.

  14. Role of viral replication in extrahepatic syndromes related to hepatitis B virus infection.

    Science.gov (United States)

    Mason, A

    2006-03-01

    Approximately 20% of patients with hepatitis B virus (HBV) infection may experience extrahepatic disease. These manifestations include a viral prodrome with a serum sickness-like syndrome, polyarteritis nodosa, glomerulonephritis, as well as various neurological and dermatologic diseases amongst other manifestations. The viral pathogenesis is not well understood and has been difficult to study due to the lack of an animal model of HBV-related extrahepatic disease. Deposition of immune complexes and activation of the complement cascade has been most widely studied. However, circulating immune complexes are physiologic and occur more frequently than extrahepatic disease. Also, HBV-related extrahepatic syndromes occur in the absence of immune complex formation. Several studies support the notion that HBV replication in extrahepatic tissues may also precipitate disease but extrahepatic replication has commonly been observed without any apparent cytopathic or immune related tissue damage. It is clear that suppression of viral replication with antiviral therapy or spontaneous viral clearance positively correlates with resolution of extrahepatic disease. The use of continuous immunosuppressive therapy has largely been abandoned with the advent of robust antiviral strategies to manage disease. These data support the notion that a combination of factors including inadequate clearance immune complexes and viral replication in extrahepatic tissues play an important role in the pathogenesis. This conceptual framework is potentially significant as it emphasizes the importance of antiviral treatment in the management of extrahepatic disease.

  15. Airway Clearance Devices for Cystic Fibrosis

    Science.gov (United States)

    2009-01-01

    Executive Summary Objective The purpose of this evidence-based analysis is to examine the safety and efficacy of airway clearance devices (ACDs) for cystic fibrosis and attempt to differentiate between devices, where possible, on grounds of clinical efficacy, quality of life, safety and/or patient preference. Background Cystic fibrosis (CF) is a common, inherited, life-limiting disease that affects multiple systems of the human body. Respiratory dysfunction is the primary complication and leading cause of death due to CF. CF causes abnormal mucus secretion in the airways, leading to airway obstruction and mucus plugging, which in turn can lead to bacterial infection and further mucous production. Over time, this almost cyclical process contributes to severe airway damage and loss of respiratory function. Removal of airway secretions, termed airway clearance, is thus an integral component of the management of CF. A variety of methods are available for airway clearance, some requiring mechanical devices, others physical manipulation of the body (e.g. physiotherapy). Conventional chest physiotherapy (CCPT), through the assistance of a caregiver, is the current standard of care for achieving airway clearance, particularly in young patients up to the ages of six or seven. CF patients are, however, living much longer now than in decades past. The median age of survival in Canada has risen to 37.0 years for the period of 1998-2002 (5-year window), up from 22.8 years for the 5-year window ending in 1977. The prevalence has also risen accordingly, last recorded as 3,453 in Canada in 2002, up from 1,630 in 1977. With individuals living longer, there is a greater need for independent methods of airway clearance. Airway Clearance Devices There are at least three classes of airway clearance devices: positive expiratory pressure devices (PEP), airway oscillating devices (AOD; either handheld or stationary) and high frequency chest compression (HFCC)/mechanical percussion (MP

  16. VIRAL HEPATITIS E DIAGNOSTICS

    Directory of Open Access Journals (Sweden)

    E. Yu. Malinnikova

    2013-01-01

    Full Text Available Abstract. The results of clinical and epidemiological studies conducted in the M.P. Chumakov’ Research Institute of Poliomyelitis and Viral Encephalitis and in the different research institutions of the world have been summarized in the current article. Data on etiology, pathogenesis, clinical symptoms, epidemiology and prevention of hepatitis E are presented. Increasing of significance of this infection for health care system in Russia is emphasized . The actual problems of hepatitis E (autochthonic hepatitis E, hepatitis E as zoonosis, chronic hepatitis E are discussed.

  17. Interleukin-28 and hepatitis C virus genotype-4: Treatment-induced clearance and liver fibrosis

    Institute of Scientific and Technical Information of China (English)

    Moutaz Derbala; Nasser Rizk; Fatima Shebl; Saad Alkaabi; Nazeeh Eldweik; Anil John; Manik Sharma

    2012-01-01

    .92; 95%C1:2.09-16.76).Similarly,patients with CT genotype had SVR more often than patients with TT genotype(aOR =2.48; 95%CI:0.94-6.52).Carrying at least one copy of the C allele (genotypes CT and CC) had almost 8 times the probability of ETR compared to those with genotype rs12979860 TT (aOR =7.87; 95%CI:2.84-21.82),and approximately 3 times the odds of SVR compared to those with genotype rs12979860 TT (aOR =3.46; 95%CI:1.37-8.74).In addition,data were consistent with a significant gene-dose relationship (aOR =4.05/allele; 95%CI:2.27-7.22).The association between rs12979860 genotype and SVR was similar among those who achieved and those who did not achieve SVR.CONCLUSION:In HCV-genotype 4 patients,rs12979860 is a sensitive predictor of viral clearance,independent of viral load,age,gender or fibrosis,with no similar relation to severity of fibrosis.

  18. Replication and clearance of respiratory syncytial virus - Apoptosis is an important pathway of virus clearance after experimental infection with bovine respiratory syncytial virus

    DEFF Research Database (Denmark)

    Viuff, B.; Tjørnehøj, Kirsten; Larsen, Lars Erik

    2002-01-01

    Human respiratory syncytial virus is an important cause of severe respiratory disease in young children, the elderly, and in immunocompromised adults. Similarly, bovine respiratory syncytial virus (BRSV) is causing severe, sometimes fatal, respiratory disease in calves. Both viruses are pneumovirus...... and clearance in a natural target animal. Replication of BRSV was demonstrated in the luminal part of the respiratory epithelial cells and replication in the upper respiratory tract preceded the replication in the lower respiratory tract. Virus excreted to the lumen of the respiratory tract was cleared...... and the infections with human respiratory syncytial. virus and BRSV have similar clinical, pathological, and epidemiological characteristics. In this study we used experimental BRSV infection in calves as a model of respiratory syncytial virus infection to demonstrate important aspects of viral replication...

  19. Load Measurements

    DEFF Research Database (Denmark)

    Kock, Carsten Weber; Vesth, Allan

    The report describes Load measurements carried out on a given wind turbine. The aim of the measurement program regarding the loads on the turbine is to verify the basic characteristics of the wind turbine and loads on the blades, the rotor and the tower, using [Ref 1], [Ref2] and [Ref 3]. Regarding...... the fatigue loads, the rotor, blades and tower moments are presented. The fatigue loads are evaluated using rainflow counting described in detail in Ref. [1]. The 1Hz equivalent load ranges are calculated at different wind speeds. All information regarding the instrumentation is collected in [ref 4] and [ref...

  20. Viral infections of rabbits.

    Science.gov (United States)

    Kerr, Peter J; Donnelly, Thomas M

    2013-05-01

    Viral diseases of rabbits have been used historically to study oncogenesis (e.g. rabbit fibroma virus, cottontail rabbit papillomavirus) and biologically to control feral rabbit populations (e.g. myxoma virus). However, clinicians seeing pet rabbits in North America infrequently encounter viral diseases although myxomatosis may be seen occasionally. The situation is different in Europe and Australia, where myxomatosis and rabbit hemorrhagic disease are endemic. Advances in epidemiology and virology have led to detection of other lapine viruses that are now recognized as agents of emerging infectious diseases. Rabbit caliciviruses, related to rabbit hemorrhagic disease, are generally avirulent, but lethal variants are being identified in Europe and North America. Enteric viruses including lapine rotavirus, rabbit enteric coronavirus and rabbit astrovirus are being acknowledged as contributors to the multifactorial enteritis complex of juvenile rabbits. Three avirulent leporid herpesviruses are found in domestic rabbits. A fourth highly pathogenic virus designated leporid herpesvirus 4 has been described in Canada and Alaska. This review considers viruses affecting rabbits by their clinical significance. Viruses of major and minor clinical significance are described, and viruses of laboratory significance are mentioned.

  1. [Ratio of amylase clearance and creatinine clearance in the diagnosis of acute pancreatitis].

    Science.gov (United States)

    Haffter, D; Reichlin, B; Gyr, K

    1981-05-30

    In 21 healthy volunteers the ratio of amylase clearance and creatinine clearance (Cam/Ccr) was determined in urine collected at admission, after a 1-hour collection period and after a 2-hour collection period. The normal values were 1.8 +/- 1.6%, 1.9 +/- 2% and 2.0 +/- 1.7% respectively. They were comparable with those published by others. The reproducibility of the method was acceptable (r = 0.62). When compared with serum amylase determinations, Cam/Ccr showed neither better sensitivity in 19 patients suffering an acute episode of proven pancreatitis, nor better specificity in 19 patients with acute abdomen but no evidence of pancreatitis.

  2. Cytokine determinants of viral tropism

    OpenAIRE

    McFadden, Grant; Mohamed, Mohamed R.; Rahman, Masmudur M.; Bartee, Eric

    2009-01-01

    The specificity of a given virus for a ceil type, tissue or species — collectively known as viral tropism — is an important factor in determining the outcome of viral infection in any particular host. Owing to the increased prevalence of zoonotic infections and the threat of emerging and re-emerging pathogens, gaining a better understanding of the factors that determine viral tropism has become particularly important. In this Review, we summarize our current understanding of the central role ...

  3. [A retrospective study on HBsAg clearance rate after antiviral therapy in children with HBeAg-positive chronic hepatitis B aged 1-7 years].

    Science.gov (United States)

    Zhu, S S; Dong, Y; Xu, Z Q; Wang, L M; Chen, D W; Gan, Y; Wang, F C; Yan, J G; Cao, L L; Wang, P; Zhang, H F

    2016-10-20

    Objective: To investigate the HBsAg clearance rate after antiviral therapy in children with HBeAg-positive chronic hepatitis B (CHB) aged 1-7 years. Methods: A retrospective analysis was performed for the HBsAg clearance rate in 293 children who were hospitalized in 302 Hospital of PLA from June 2006 to December 2013, met the inclusion criteria, received antiviral therapy, and were followed up for at least 6 months after the withdrawal of antiviral therapy. The t-test or the rank sum test was applied according to the distribution of continuous data, and the chi-square test was used for comparison of categorical data. Results: The HBsAg positive rate of children's mothers was 91.1%. In the age groups of >1-≤2 years, >2-≤3 years, >3-≤4 years, >4-≤5 years, >5-≤6 years, and >6-≤7 years, the HBsAg clearance rates were 66.1%, 65.5%, 45.7%, 41.3%, 20.6%, and 27.6%, respectively. There were significant differences in HBsAg clearance rate between the age groups of >1-≤3 years and >3-≤5 years, >1-≤3 years and >5-≤7 years, and >3-≤5 years and >5-≤7 years (P = 0.001, 0.000, and 0.008). Of all children, 64.8% were boys, among whom 41.1% achieved HBsAg clearance, and 35.2% were girls, among whom 61.2% achieved HBsAg clearance; there was a significant difference in HBsAg clearance rate between boys and girls (P = 0.001). The children with pretreatment alanine aminotransferase (ALT) levels of ≤80 IU/L, > 80 IU/L, ≤200 IU/L, and > 200 IU/L had HBsAg clearance rates of 40.7%, 51.2%, 47.6%, and 49.4%, respectively; there were no significant differences in HBsAg clearance rate between the ALT ≤80 IU/L and ALT > 80 IU/L groups and the ALT ≤200 IU/L and ALT > 200 IU/L groups (P = 0.101 and 0.778). There was no significant difference in HBsAg clearance rate between the pretreatment HBV DNA load clearance rate of 57.1%, and 85% had genotype C and an HBsAg clearance rate of 39.5%; there was no significant difference in HBsAg clearance rate between the

  4. Influenza infection suppresses NADPH oxidase-dependent phagocytic bacterial clearance and enhances susceptibility to secondary MRSA infection

    Science.gov (United States)

    Sun, Keer; Metzger, Dennis W.

    2014-01-01

    Methicillin-resistant S. aureus (MRSA) has emerged as a leading contributor to mortality during recent influenza pandemics. The mechanism for this influenza-induced susceptibility to secondary S. aureus infection is poorly understood. Here we show that innate antibacterial immunity was significantly suppressed during the recovery stage of influenza infection, despite the fact that MRSA super-infection had no significant effect on viral burdens. Compared to mice infected with bacteria alone, post-influenza MRSA infected mice exhibited impaired bacterial clearance, which was not due to defective phagocyte recruitment, but rather coincided with reduced intracellular reactive oxygen species (ROS) levels in alveolar macrophages and neutrophils. NADPH oxidase is responsible for ROS production during phagocytic bacterial killing, a process also known as oxidative burst. We found that gp91phox-containing NADPH oxidase activity in macrophages and neutrophils was essential for optimal bacterial clearance during respiratory MRSA infections. In contrast to WT animals, gp91phox−/− mice exhibited similar defects in MRSA clearance before and after influenza infection. Using gp91phox+/− mosaic mice, we further demonstrate that influenza infection inhibits a cell-intrinsic contribution of NADPH oxidase to phagocyte bactericidal activity. Together, our results establish that influenza infection suppresses NADPH oxidase-dependent bacterial clearance and leads to susceptibility to secondary MRSA infection. PMID:24563256

  5. Dynamics of viral replication in blood and lymphoid tissues during SIVmac251 infection of macaques

    Directory of Open Access Journals (Sweden)

    Mannioui Abdelkrim

    2009-01-01

    Full Text Available Abstract Background Extensive studies of primary infection are crucial to our understanding of the course of HIV disease. In SIV-infected macaques, a model closely mimicking HIV pathogenesis, we used a combination of three markers -- viral RNA, 2LTR circles and viral DNA -- to evaluate viral replication and dissemination simultaneously in blood, secondary lymphoid tissues, and the gut during primary and chronic infections. Subsequent viral compartmentalization in the main target cells of the virus in peripheral blood during the chronic phase of infection was evaluated by cell sorting and viral quantification with the three markers studied. Results The evolutions of viral RNA, 2LTR circles and DNA levels were correlated in a given tissue during primary and early chronic infection. The decrease in plasma viral load principally reflects a large decrease in viral replication in gut-associated lymphoid tissue (GALT, with viral RNA and DNA levels remaining stable in the spleen and peripheral lymph nodes. Later, during chronic infection, a progressive depletion of central memory CD4+ T cells from the peripheral blood was observed, accompanied by high levels of viral replication in the cells of this subtype. The virus was also found to replicate at this point in the infection in naive CD4+ T cells. Viral RNA was frequently detected in monocytes, but no SIV replication appeared to occur in these cells, as no viral DNA or 2LTR circles were detected. Conclusion We demonstrated the persistence of viral replication and dissemination, mostly in secondary lymphoid tissues, during primary and early chronic infection. During chronic infection, the central memory CD4+ T cells were the major site of viral replication in peripheral blood, but viral replication also occurred in naive CD4+ T cells. The role of monocytes seemed to be limited to carrying the virus as a cargo because there was an observed lack of replication in these cells. These data may have important

  6. Tip Clearance Control Using Plasma Actuators

    Science.gov (United States)

    2007-03-01

    Clearance Control Using Plasma Actuators 4 posed by Denton (1993). A number of investigators have used partial shrouds, or " winglet " designs to...main molded blade with a span of 3.42 in., a removable molded blade segment with a span of 0.1875 in., and removable blade tip winglets made of glass...segment and the main blade to vary the distance between the blade end and the front wall of the cascade section. The winglets were machined using a

  7. The economics of landmine clearance in Afghanistan.

    Science.gov (United States)

    Harris, Geoff

    2002-03-01

    This paper presents an economic evaluation of landmine clearance in Afghanistan. The main benefits comprise increased agricultural output, saved transport time and running costs, saved human casualties and the saved costs of supporting refugees and displaced persons. An investment of US$100 million between 1988 and 1998 is estimated to provide annual benefits of $50.3 million per annum between 1999 and 2008. This translates into net present values of between $935 and $1,744 million, depending on the rate of discount used. This contrasts with the negative NPVs estimated for several other countries.

  8. Amylase creatinine clearance ratio after biliary surgery.

    Science.gov (United States)

    Donaldson, L A; McIntosh, W; Joffe, S N

    1977-01-01

    The amylase creatinine clearance ratio (ACCR) is considered to be a more sensitive index of acute pancreatitis than the serum amylase level. Serial ACCR estimations were undertaken in 25 patients undergoing an elective cholecystectomy. Using accepted criteria, 28% of these patients developed, in the postoperative period, biochemical evidence of pancreatic gland damage, although the serum amylase level remained normal. This raised ACCR was particularly noted in patients who had undergone an exploration of the common bile duct. The ACCR would appear to be a more sensitive index of pancreatic gland disruption secondary to biliary surgery than the serum amylase level.

  9. Load Measurements

    DEFF Research Database (Denmark)

    Vesth, Allan; Kock, Carsten Weber

    The report describes Load measurements carried out on a given wind turbine. The aim of the measurement program regarding the loads on the turbine is to verify the basic characteristics of the wind turbine and loads on the blades, the rotor and the tower, using [Ref 1], [Ref2] and [Ref 3]. Regardi...

  10. Viral causes of diarrhea.

    Science.gov (United States)

    Goodgame, R W

    2001-09-01

    Viruses are important causes of diarrhea. In healthy adults, the main clinical manifestation is acute, self-limited gastroenteritis. Advances in molecular diagnostics have shown that epidemics of acute gastroenteritis most frequently are due to caliciviruses spread through contaminated food or through person-to-person contact. Application of similar technology is needed to make a definitive statement about the role of such candidate viruses as rotavirus, astrovirus, and adenovirus as the cause of nonepidemic acute gastroenteritis in adults. Rarely a previously healthy adult gets acute CMV colitis. CMV and EBV mainly cause diarrhea in immunocompromised patients, however. Advances in prophylaxis and treatment have reduced the frequency and severity of these diseases. Acute infantile gastroenteritis is caused by rotavirus, calcivirus, astrovirus, and adenovirus. These viral diseases of the gut are seen by the physician as routine and rare clinical problems.

  11. Viral quasispecies evolution.

    Science.gov (United States)

    Domingo, Esteban; Sheldon, Julie; Perales, Celia

    2012-06-01

    Evolution of RNA viruses occurs through disequilibria of collections of closely related mutant spectra or mutant clouds termed viral quasispecies. Here we review the origin of the quasispecies concept and some biological implications of quasispecies dynamics. Two main aspects are addressed: (i) mutant clouds as reservoirs of phenotypic variants for virus adaptability and (ii) the internal interactions that are established within mutant spectra that render a virus ensemble the unit of selection. The understanding of viruses as quasispecies has led to new antiviral designs, such as lethal mutagenesis, whose aim is to drive viruses toward low fitness values with limited chances of fitness recovery. The impact of quasispecies for three salient human pathogens, human immunodeficiency virus and the hepatitis B and C viruses, is reviewed, with emphasis on antiviral treatment strategies. Finally, extensions of quasispecies to nonviral systems are briefly mentioned to emphasize the broad applicability of quasispecies theory.

  12. A unified framework of immunological and epidemiological dynamics for the spread of viral infections in a simple network-based population

    Directory of Open Access Journals (Sweden)

    Vickers David M

    2007-12-01

    Full Text Available Abstract Background The desire to better understand the immuno-biology of infectious diseases as a broader ecological system has motivated the explicit representation of epidemiological processes as a function of immune system dynamics. While several recent and innovative contributions have explored unified models across cellular and organismal domains, and appear well-suited to describing particular aspects of intracellular pathogen infections, these existing immuno-epidemiological models lack representation of certain cellular components and immunological processes needed to adequately characterize the dynamics of some important epidemiological contexts. Here, we complement existing models by presenting an alternate framework of anti-viral immune responses within individual hosts and infection spread across a simple network-based population. Results Our compartmental formulation parsimoniously demonstrates a correlation between immune responsiveness, network connectivity, and the natural history of infection in a population. It suggests that an increased disparity between people's ability to respond to an infection, while maintaining an average immune responsiveness rate, may worsen the overall impact of an outbreak within a population. Additionally, varying an individual's network connectivity affects the rate with which the population-wide viral load accumulates, but has little impact on the asymptotic limit in which it approaches. Whilst the clearance of a pathogen in a population will lower viral loads in the short-term, the longer the time until re-infection, the more severe an outbreak is likely to be. Given the eventual likelihood of reinfection, the resulting long-run viral burden after elimination of an infection is negligible compared to the situation in which infection is persistent. Conclusion Future infectious disease research would benefit by striving to not only continue to understand the properties of an invading microbe, or

  13. Analysis of the Viral Load and Clinical Features of Children With Hand,Foot and Mouth Disease by Different Enteroviruses%不同肠道病毒感染手足口病患儿病毒载量及临床特征对比分析

    Institute of Scientific and Technical Information of China (English)

    陈苏; 杜潘艳; 郑红; 王宝林; 高翠红; 张双

    2016-01-01

    Objective To analyze the viral load and clinical features of children with hand,foot and mouth disease (HFMD)by EV71 and CoxA16. Methods A total of 430 children who were definitely diagnosed with HFMD in the Department of Pediatrics in Tangshan Women and Children Health - care Hospital from May to September in 2015 were enrolled. According to clinical symptoms,physical signs and species of virus,the children were divided into EV71 mild group(162 cases),EV71 severe group(87 cases),CoxA16 mild group(158 cases)and CoxA16 severe group(23 cases). Throat swabs of the children were collected and the RNA of EV71 and CoxA16 was detected by real - time fluorescent quantitative RT-qPCR method,and viral load was calculated. Length of disease,temperature,length of fever,dental ulcer,salivation,cough,hand rash,foot rash, somnolence,convulsion,vomit,change of consciousness,limb jitter,and myospasm of the children were recorded. Results Cycle threshold(Ct value)shown by standard curve had highly negative correlation with the viral load( r = - 1. 000,P 0. 05). EV71 severe group and CoxA16 severe group had longer length of disease than EV71 mild group and CoxA16 mild group(P 0. 05). EV71 severe group and CoxA16 severe group had higher incidence rate of the length of fever ≥3 d than EV71 mild group and CoxA16 mild group(P 0.05)。EV71重度组、CoxA16重度组 HFMD 患儿病程较 EV71轻度组、CoxA16轻度组延长(P 0.05)。EV71重度组、CoxA16重度组 HFMD 患儿热程≥3 d 发生率较 EV71轻度组、CoxA16轻度组升高(P <0.007);EV71重度组、CoxA16重度组 HFMD 患儿体温≥38.5℃+热程≥3 d 发生率较 EV71轻度组、CoxA16轻度组升高,EV71轻度组 HFMD 患儿体温≥38.5℃+热程≥3 d发生率较 CoxA16轻度组升高,EV71重度组 HFMD 患儿体温≥38.5℃+热程≥3 d 发生率较 CoxA16重度组升高(P <0.007);CoxA16轻度组、CoxA16重度组 HFMD 患儿咳嗽、手部出疹数≥15个(

  14. Correlation among interferon-gamma gene polymorphism, viral load high-risk human papilloma virus ;remains and prognosis after loop electrosurgical excision procedure for CIN patients%高危型HPV载量及IFNγ基因多态性与LEEP术后CIN患者预后的相关性

    Institute of Scientific and Technical Information of China (English)

    陈艳; 林琳; 贾志强; 陈尼娅

    2015-01-01

    目的:探讨高危型人乳头状瘤病毒(HPV)载量及γ干扰素(IFNγ)基因多态性与宫颈上皮内瘤变(CIN)患者经环状电圈切除(LEEP)术后病灶残留或复发的关系,以及发病过程中的相关性。方法:所选来自本院门诊或住院行LEEP术的HPV阳性患者共439例,并选取同期体检HPV阴性的健康女性120例作为对照,采用基因测序方法检测IFNγ基因多态性,术后3、6、9、12个月时复查高危型HPVDNA及宫颈新柏氏液基细胞学(TCT)检测。结果:IFNγ基因多态性rs243056l位点TT基因型为HPV感染发病的保护因素(OR为0.471,95%CI:0.283~0.783;x2=8.702;P=0.003),AA基因型为HPV感染发病的危险因素(OR为1.688,95%CI:1.108~2.572;x2=6.005;P=0.014),术前及术后3个月HPV载量与病灶残留/复发相关(P<0.05)。Kaplan-Meier分析结果显示,AA与TT基因型HPV感染累积阴性率有显著差异(log-rank=15.414,P<0.001),AA基因型女性HPV感染的累积阴性率最低,病灶残留/复发率为45.65%。结论:术前及术后3个月高危型HPV载量与CIN的发生、进展及CIN患者LEEP术预后有关。IFNγ基因rs2430561位点多态性影响女性宫颈HPV的易感性,AA基因型女性感染风险更高,并易于HPV感染的持续和复发。%Objective:To investigate the association of interferon-gamma gene polymorphisms and the cor-relation between viral load remains and recidivation after loop ment for CIN patients. Methods:Performed gene analysis was used for detection of polymorphisms in interferon-gamma gene in 439 HPV positive patients under-gone the LEEP treatment for CIN and 120 HPV negative normal controls, reviewed high-risk HPV DNA and cer-vix uterus TCT were reviewed in 3, 6, 9 and 12 months after treatment. Results:That the individuals with the TT genotype showed statistically signiifcant had protection against HPV infection (OR=0.471, 95%CI=0.283~0.783;x2=8.702, P=0

  15. 阿德福韦酯与恩替卡韦治疗低病毒载量代偿期乙肝肝硬化疗效比较%Comparison of adefovir and entecavir in treatment with low viral load hepatitis B virus related compensated cirrhosis

    Institute of Scientific and Technical Information of China (English)

    毛创杰; 王丽; 胡蓉; 曾义岚; 张琼; 康信通

    2015-01-01

    Objectives To compare the curative effect of adefovir dipivoxil ( ADV) and entecavir ( ETV) in the treatment of low viral load decompensated liver cirrhosis .Methods From 2011 Jan to 2012 June, 96 cases of low viral load decompensated liver cirrhosis caused by hepatitis B virus ( HBV-DNA 0.05);treated for 12 months, ADV group’ s HBeAg serum virological breakthrough rate was 16.7% and 2.1%, ETV group were 14.6% and 4.2%, the difference was not statistically significant ( P >0.05); treated for 12 months, 2 groups’ ALT, TB, Alb, PT were significantly improved ( P 0.05).The se-rum creatinine ( SCr) and lactic acid ( LA) more than the normal value of the upper limit were not found in both of the two groups.ADV group died of 1 case (2.1%), and there was no mortality in ETV group.Conclusion Adefovir dipivoxil or en entecavir treatment for low viral load compensated hepatitis B cirrhosis can significantly inhibited HBV -DNA replication, im-prove liver function indicators , reduce incidence of decompensated , its worthy of clinical application .%目的:比较阿德福韦酯( ADV)与恩替卡韦( ETV)治疗低病毒载量代偿期乙肝肝硬化患者的疗效。方法2011年1月—2012年6月选取低病毒载量代偿期乙肝肝硬化( HBV DNA均<2ˇ.0×104拷贝/ml )患者96例,按照随机数字表分为2组,其中48例接受阿德福韦酯抗病毒治疗( ADV组),48例接受恩替卡韦抗病毒治疗( ETV组),每1~3个月检测患者肝功能[丙氨酸氨基转移酶(ALT)、总胆红素(TB)、白蛋白(Alb)]、肾功能、甲胎蛋白、乙肝三系、血清HBV DNA、凝血酶原时间( PT)、肝脏B型超声或CT检查,随访12个月比较疗效及不良反应和病死率。结果 ADV组和ETV组12个月后血清HBV DNA 阴转率均为100%,比较差异无统计学意义( P >0.05);ADV组治疗12个月HBeAg血清转换率及病毒学突破率为16.7%、2.1%,ETV组分别为14.6%、4

  16. CSF clearance in Alzheimer Disease measured with dynamic PET.

    Science.gov (United States)

    de Leon, Mony J; Li, Yi; Okamura, Nobuyuki; Tsui, Wai H; Saint Louis, Les A; Glodzik, Lidia; Osorio, Ricardo S; Fortea, Juan; Butler, Tracy; Pirraglia, Elizabeth; Fossati, Silvia; Kim, Hee-Jin; Carare, Roxana O; Nedergaard, Maiken; Benveniste, Helene; Rusinek, Henry

    2017-03-16

    Evidence supporting the hypothesis that reduced cerebrospinal fluid (CSF) clearance is involved in the pathophysiology of Alzheimer's disease (AD) comes from primarily from rodent models. However, unlike rodents where predominant extra-cranial CSF egress is via olfactory nerves traversing the cribriform plate, human CSF clearance pathways are not well characterized. Using dynamic Positron Emission Tomography (PET) with (18)F-THK5117 a tracer for tau pathology, the ventricular CSF time activity was used as a biomarker for CSF clearance. We tested three hypotheses: 1. Extra-cranial CSF is detected at the superior turbinates; 2. CSF clearance is reduced in AD; and 3. CSF clearance is inversely associated with amyloid deposition. Methods: 15 subjects, 8 with AD and 7 normal control volunteers were examined with (18)F-THK5117. 10 subjects additionally received (11)C-PiB PET scans and 8 were PiB positive. Ventricular time activity curves (TAC) of (18)F-THK5117 were used to identify highly correlated TAC from extra-cranial voxels. Results: For all subjects, the greatest density of CSF positive extra-cranial voxels was in the nasal turbinates. Tracer concentration analyses validated the superior nasal turbinate CSF signal intensity. AD patients showed ventricular tracer clearance reduced by 23% and 66% fewer superior turbinate CSF egress sites. Ventricular CSF clearance was inversely associated with amyloid deposition. Conclusion: The human nasal turbinate is part of the CSF clearance system. Lateral ventricle and superior nasal turbinates CSF clearance abnormalities are found in AD. Ventricular CSF clearance reductions are associated with increased brain amyloid depositions. These data suggest that PET measured CSF clearance is a biomarker of potential interest in AD and other neurodegenerative diseases.

  17. Genetic Variation of HIV: Viral Load and Genotypic Diversity in Relation to Viral Pathogenesis and Treatment

    Science.gov (United States)

    1993-07-20

    0 Z MAMA -0341 10/25 11 705 64 0 N ADFR-O 194 05/10 If 703 387 0 N BECH-0171 03109 11 678 5% 0 N MALE-0264 07/26 Ii1 644 3138 0 N ROJO-0331 11/29 11...or III RIPH 0179 1060 40.800 39 0 0 HI{D) 1099 623 36.000 0 0 0 ATKA 0361 760 9.400 0 0 0 HOJU 0143 720 36.900 0 0 0 MAMA 0341 706 113.400 31 0 0 ADFR...biologically unique strains of HIV-2. Annual Meeting. Laboratory for Tumor Cell Biolov. Bethesda, Maryland, 1991. 8. SHAW, G.M., G. Pan, SJ. Clark, M.S. Saag

  18. Understanding MHC class I presentation of viral antigens by human dendritic cells as a basis for rational design of therapeutic vaccines

    NARCIS (Netherlands)

    N. van Montfoort (Nadine); E. van der Aa (Evelyn); A.M. Woltman (Andrea)

    2014-01-01

    textabstractEffective viral clearance requires the induction of virus-specific CD8+ cytotoxic T lymphocytes (CTL). Since dendritic cells (DC) have a central role in initiating and shaping virus-specific CTL responses, it is important to understand how DC initiate virus-specific CTL responses. Some v

  19. Sphingolipids in viral infection.

    Science.gov (United States)

    Schneider-Schaulies, Jürgen; Schneider-Schaulies, Sibylle

    2015-06-01

    Viruses exploit membranes and their components such as sphingolipids in all steps of their life cycle including attachment and membrane fusion, intracellular transport, replication, protein sorting and budding. Examples for sphingolipid-dependent virus entry are found for: human immunodeficiency virus (HIV), which besides its protein receptors also interacts with glycosphingolipids (GSLs); rhinovirus, which promotes the formation of ceramide-enriched platforms and endocytosis; or measles virus (MV), which induces the surface expression of its own receptor CD150 via activation of sphingomyelinases (SMases). While SMase activation was implicated in Ebola virus (EBOV) attachment, the virus utilizes the cholesterol transporter Niemann-Pick C protein 1 (NPC1) as 'intracellular' entry receptor after uptake into endosomes. Differential activities of SMases also affect the intracellular milieu required for virus replication. Sindbis virus (SINV), for example, replicates better in cells lacking acid SMase (ASMase). Defined lipid compositions of viral assembly and budding sites influence virus release and infectivity, as found for hepatitis C virus (HCV) or HIV. And finally, viruses manipulate cellular signaling and the sphingolipid metabolism to their advantage, as for example influenza A virus (IAV), which activates sphingosine kinase 1 and the transcription factor NF-κB.

  20. Dengue viral infections

    Directory of Open Access Journals (Sweden)

    Gurugama Padmalal

    2010-01-01

    Full Text Available Dengue viral infections are one of the most important mosquito-borne diseases in the world. Presently dengue is endemic in 112 countries in the world. It has been estimated that almost 100 million cases of dengue fever and half a million cases of dengue hemorrhagic fever (DHF occur worldwide. An increasing proportion of DHF is in children less than 15 years of age, especially in South East and South Asia. The unique structure of the dengue virus and the pathophysiologic responses of the host, different serotypes, and favorable conditions for vector breeding have led to the virulence and spread of the infections. The manifestations of dengue infections are protean from being asymptomatic to undifferentiated fever, severe dengue infections, and unusual complications. Early recognition and prompt initiation of appropriate supportive treatment are often delayed resulting in unnecessarily high morbidity and mortality. Attempts are underway for the development of a vaccine for preventing the burden of this neglected disease. This review outlines the epidemiology, clinical features, pathophysiologic mechanisms, management, and control of dengue infections.

  1. Emerging zoonotic viral diseases.

    Science.gov (United States)

    Wang, L-F; Crameri, G

    2014-08-01

    Zoonotic diseases are infectious diseases that are naturally transmitted from vertebrate animals to humans and vice versa. They are caused by all types of pathogenic agents, including bacteria, parasites, fungi, viruses and prions. Although they have been recognised for many centuries, their impact on public health has increased in the last few decades due to a combination of the success in reducing the spread of human infectious diseases through vaccination and effective therapies and the emergence of novel zoonotic diseases. It is being increasingly recognised that a One Health approach at the human-animal-ecosystem interface is needed for effective investigation, prevention and control of any emerging zoonotic disease. Here, the authors will review the drivers for emergence, highlight some of the high-impact emerging zoonotic diseases of the last two decades and provide examples of novel One Health approaches for disease investigation, prevention and control. Although this review focuses on emerging zoonotic viral diseases, the authors consider that the discussions presented in this paper will be equally applicable to emerging zoonotic diseases of other pathogen types.

  2. [Mucociliary clearance function and medicamentous modification].

    Science.gov (United States)

    Konrad, F

    1996-09-01

    Mucociliary clearance represents a complex self-cleaning mechanism of the lung and is based on the functional unity of ciliated columnar cells and the special viscoelastic properties of the secretion produced in the tracheobronchial system. It has been known for a long time that intubation and mechanical ventilation can impair mucous transport and lead to morphological damage to the tracheobronchial mucosa. Recent studies made it clear, however, that mechanical ventilation during anaesthesia using an appropriate anaesthesiological technique has no deleterious effect on mucus transport in patients with healthy lungs. Ventilated patients in the intensive-care unit frequently have impaired mucus transport, which is associated with the development of retention of secretion and nosocomial pneumonia. In these patients a number of factors combine to form a formidable potential insult to the mucociliary transport mechanism. Numerous drugs can affect mucociliary transport. Beta-mimetics and theophylline, in particular, have a favourable effect on mucociliary transport, whereas the effect of mucolytic agents is controversial.

  3. Nonlinear Dynamics Behaviors of a Rotor Roller Bearing System with Radial Clearances and Waviness Considered

    Institute of Scientific and Technical Information of China (English)

    Wang Liqin; Cui Li; Zheng Dezhi; Gu Le

    2008-01-01

    A rotor system supported by roller bearings displays very complicated nonlinear behaviors due to nonlinear Hertzian contact forces, radial clearances and bearing waviness. This paper presents nonlinear bearing forces of a roller bearing under four-dimensional loads and establishes 4-DOF dynamics equations of a rotor roller bearing system. The methods of Newmark-β and of Newton-Laphson are used to solve the nonlinear equations. The dynamics behaviors of a rigid rotor system are studied through the bifurcation, the Poincar bility caused by the quasi-periodic bifurcation, the periodic-doubling bifurcation and chaos routes as the rotational speed increases.Clearances, outer race waviness, inner race waviness, roller waviness, damping, radial forces and unbalanced forces-all these bring a significant influence to bear on the system stability. As the clearance increases, the dynamics behaviors become complicated with the number and the scale of instable regions becoming larger. The vibration frequencies induced by the roller bearing waviness and the orders of the waviness might cause severe vibrations. The system is able to eliminate non-periodic vibration by reasonable choice and optimization of the parameters.

  4. Comparative analysis of measures of viral reservoirs in HIV-1 eradication studies.

    Directory of Open Access Journals (Sweden)

    Susanne Eriksson

    2013-02-01

    Full Text Available HIV-1 reservoirs preclude virus eradication in patients receiving highly active antiretroviral therapy (HAART. The best characterized reservoir is a small, difficult-to-quantify pool of resting memory CD4(+ T cells carrying latent but replication-competent viral genomes. Because strategies targeting this latent reservoir are now being tested in clinical trials, well-validated high-throughput assays that quantify this reservoir are urgently needed. Here we compare eleven different approaches for quantitating persistent HIV-1 in 30 patients on HAART, using the original viral outgrowth assay for resting CD4(+ T cells carrying inducible, replication-competent viral genomes as a standard for comparison. PCR-based assays for cells containing HIV-1 DNA gave infected cell frequencies at least 2 logs higher than the viral outgrowth assay, even in subjects who started HAART during acute/early infection. This difference may reflect defective viral genomes. The ratio of infected cell frequencies determined by viral outgrowth and PCR-based assays varied dramatically between patients. Although strong correlations with the viral outgrowth assay could not be formally excluded for most assays, correlations achieved statistical significance only for integrated HIV-1 DNA in peripheral blood mononuclear cells and HIV-1 RNA/DNA ratio in rectal CD4(+ T cells. Residual viremia was below the limit of detection in many subjects and did not correlate with the viral outgrowth assays. The dramatic differences in infected cell frequencies and the lack of a precise correlation between culture and PCR-based assays raise the possibility that the successful clearance of latently infected cells may be masked by a larger and variable pool of cells with defective proviruses. These defective proviruses are detected by PCR but may not be affected by reactivation strategies and may not require eradication to accomplish an effective cure. A molecular understanding of the discrepancy

  5. Encefalitis virales en la infancia

    OpenAIRE

    2013-01-01

    La encefalitis viral es una enfermedad grave que implica el compromiso inflamatorio del parénquima cerebral. Las infecciones virales del SNC ocurren con frecuencia como complicación de infecciones virales sistémicas. Más de 100 virus están implicados como agentes causales, entre los cuales el virus Herpes simplex tipo I, es el agente causal más frecuente de encefalitis no epidémica en todos los grupos poblacionales del mundo; es el responsable de los casos más graves en todas las edades. Much...

  6. Enfermedades virales emergentes y reemergentes

    OpenAIRE

    Jorge Eliécer Ossa Londoño; Ana Isabel Toro Montoya

    1996-01-01

    Los virus no son una excepción al principio de que toda forma de vida de hoyes el producto de la evolución de información gen ética preexistente. Tradicionalmente se ha reconocido que ta expresión clínica de las enfermedades virales cambia con el tiempo; molecularmente se ha demostrado que esos cambios fenotípicos son el producto de variaciones en el genoma viral. La tasa de cambio
    gen ético y fenotípico no es la misma en todos los agentes virales y ello está determinado, principal...

  7. 48 CFR 32.502-2 - Contract finance office clearance.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Contract finance office clearance. 32.502-2 Section 32.502-2 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION... finance office clearance. The contracting officer shall obtain the approval of the contract finance...

  8. 10 CFR 95.53 - Termination of facility clearance.

    Science.gov (United States)

    2010-01-01

    ... 10 Energy 2 2010-01-01 2010-01-01 false Termination of facility clearance. 95.53 Section 95.53 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) FACILITY SECURITY CLEARANCE AND SAFEGUARDING OF NATIONAL SECURITY INFORMATION AND RESTRICTED DATA Control of Information § 95.53 Termination of facility...

  9. 48 CFR 1432.502-2 - Contract finance office clearance.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Contract finance office clearance. 1432.502-2 Section 1432.502-2 Federal Acquisition Regulations System DEPARTMENT OF THE INTERIOR... finance office clearance. The CO shall obtain approval of the bureau finance office prior to...

  10. 48 CFR 832.502-2 - Contract finance office clearance.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Contract finance office clearance. 832.502-2 Section 832.502-2 Federal Acquisition Regulations System DEPARTMENT OF VETERANS AFFAIRS... finance office clearance. Contracting officers must obtain approval from the DSPE before taking...

  11. 30 CFR 77.514 - Switchboards; passageways and clearance.

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Switchboards; passageways and clearance. 77.514 Section 77.514 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR COAL MINE... COAL MINES Electrical Equipment-General § 77.514 Switchboards; passageways and clearance....

  12. 33 CFR 160.115 - Withholding of clearance.

    Science.gov (United States)

    2010-07-01

    ... 33 Navigation and Navigable Waters 2 2010-07-01 2010-07-01 false Withholding of clearance. 160.115... § 160.115 Withholding of clearance. Each District Commander or Captain of the Port may request the Secretary of the Treasury, or the authorized representative thereof, to withhold or revoke the...

  13. 14 CFR 93.311 - Minimum terrain clearance.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 2 2010-01-01 2010-01-01 false Minimum terrain clearance. 93.311 Section 93.311 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED... of Grand Canyon National Park, AZ § 93.311 Minimum terrain clearance. Except in an emergency,...

  14. 48 CFR 245.7310-8 - Antitrust clearance.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 3 2010-10-01 2010-10-01 false Antitrust clearance. 245.7310-8 Section 245.7310-8 Federal Acquisition Regulations System DEFENSE ACQUISITION REGULATIONS SYSTEM... Antitrust clearance. When property with an acquisition cost of $3 million or more is to be sold, include...

  15. 5 CFR 720.307 - Interagency report clearance.

    Science.gov (United States)

    2010-01-01

    ... 5 Administrative Personnel 2 2010-01-01 2010-01-01 false Interagency report clearance. 720.307 Section 720.307 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT (CONTINUED) CIVIL SERVICE... Interagency report clearance. The reports contained in this regulation have been cleared in accordance...

  16. 24 CFR 58.22 - Limitations on activities pending clearance.

    Science.gov (United States)

    2010-04-01

    ... 24 Housing and Urban Development 1 2010-04-01 2010-04-01 false Limitations on activities pending clearance. 58.22 Section 58.22 Housing and Urban Development Office of the Secretary, Department of Housing... clearance. (a) Neither a recipient nor any participant in the development process, including public...

  17. Allometric scaling for predicting human clearance of bisphenol A

    Energy Technology Data Exchange (ETDEWEB)

    Collet, Séverine H., E-mail: s.collet@envt.fr; Picard-Hagen, Nicole, E-mail: n.hagen-picard@envt.fr; Lacroix, Marlène Z., E-mail: m.lacroix@envt.fr; Puel, Sylvie, E-mail: s.puel@envt.fr; Viguié, Catherine, E-mail: c.viguie@envt.fr; Bousquet-Melou, Alain, E-mail: a.bousquet-Melou@envt.fr; Toutain, Pierre-Louis, E-mail: pltoutain@wanadoo.fr; Gayrard, Véronique, E-mail: v.gayrard@envt.fr

    2015-05-01

    The investigation of interspecies differences in bisphenol A (BPA) pharmacokinetics (PK) may be useful for translating findings from animal studies to humans, identifying major processes involved in BPA clearance mechanisms, and predicting BPA PK parameters in man. For the first time, a large range of species in terms of body weight, from 0.02 kg (mice) to 495 kg (horses) was used to predict BPA clearance in man by an allometric approach. BPA PK was evaluated after intravenous administration of BPA in horses, sheep, pigs, dogs, rats and mice. A non-compartmental analysis was used to estimate plasma clearance and steady state volume of distribution and predict BPA PK parameters in humans from allometric scaling. In all the species investigated, BPA plasma clearance was high and of the same order of magnitude as their respective hepatic blood flow. By an allometric scaling, the human clearance was estimated to be 1.79 L/min (equivalent to 25.6 mL/kg.min) with a 95% prediction interval of 0.36 to 8.83 L/min. Our results support the hypothesis that there are highly efficient and hepatic mechanisms of BPA clearance in man. - Highlights: • Allometric scaling was used to predict BPA pharmacokinetic parameters in humans. • In all species, BPA plasma clearance approached hepatic blood flow. • Human BPA clearance was estimated to be 1.79 L/min.

  18. Do dialysate conductivity measurements provide conductivity clearance or ionic dialysance?

    Science.gov (United States)

    Petitclerc, T

    2006-11-01

    Dialysate conductivity measurements allow on-line estimation of urea clearance during hemodialysis session. Conductivity measurements provide a value of 'conductivity clearance' for some authors, but a value of 'ionic dialysance' for others. This paper aims at explaining which term should be the more appropriate. Clearance is a parameter defined for measuring the power of a mechanism, which aims at 'clearing' a solution by depurating some solutes. In hemodialysis, clearance measures the efficacy of patient's depuration. In contrast, dialysance measures the capability of transferring solutes between blood and dialysate. The conventional definition of dialysance, requiring the absence of convective transfer, should be generalized to the case of the usual presence of ultrafiltration during the hemodialysis session. For a solute (as urea) absent from the dialysate delivered to the dialyzer inlet, the clearance is equal to its dialysance. In order to avoid a dramatic fall in ionic concentrations during hemodialysis treatment, the clearance of ions is reduced by adding these ions in the dialysate and becomes lower than their dialysance. Conductivity measurements provide a value of electrolytes dialysance. Thus the term of 'ionic dialysance' is more appropriate than the term of 'conductivity clearance'. Nevertheless ionic dialysance represents a good estimation of urea clearance.

  19. Mechanistic evaluation of virus clearance by depth filtration.

    Science.gov (United States)

    Venkiteshwaran, Adith; Fogle, Jace; Patnaik, Purbasa; Kowle, Ron; Chen, Dayue

    2015-01-01

    Virus clearance by depth filtration has not been well-understood mechanistically due to lack of quantitative data on filter charge characteristics and absence of systematic studies. It is generally believed that both electrostatic interactions and sized based mechanical entrapment contribute to virus clearance by depth filtration. In order to establish whether the effectiveness of virus clearance correlates with the charge characteristics of a given depth filter, a counter-ion displacement technique was employed to determine the ionic capacity for several depth filters. Two depth filters (Millipore B1HC and X0HC) with significant differences in ionic capacities were selected and evaluated for their ability to eliminate viruses. The high ionic capacity X0HC filter showed complete porcine parvovirus (PPV) clearance (eliminating the spiked viruses to below the limit of detection) under low conductivity conditions (≤2.5 mS/cm), achieving a log10 reduction factor (LRF) of > 4.8. On the other hand, the low ionic capacity B1HC filter achieved only ∼2.1-3.0 LRF of PPV clearance under the same conditions. These results indicate that parvovirus clearance by these two depth filters are mainly achieved via electrostatic interactions between the filters and PPV. When much larger xenotropic murine leukemia virus (XMuLV) was used as the model virus, complete retrovirus clearance was obtained under all conditions evaluated for both depth filters, suggesting the involvement of mechanisms other than just electrostatic interactions in XMuLV clearance.

  20. 32 CFR 644.522 - Clearance of military scrap.

    Science.gov (United States)

    2010-07-01

    ... 32 National Defense 4 2010-07-01 2010-07-01 true Clearance of military scrap. 644.522 Section 644... Excess Land and Improvements § 644.522 Clearance of military scrap. Military scrap can contain or be... determining whether scrap metal will be removed should be the safety of persons coming on the land in...

  1. Clearance systems in the brain-implications for Alzheimer disease.

    Science.gov (United States)

    Tarasoff-Conway, Jenna M; Carare, Roxana O; Osorio, Ricardo S; Glodzik, Lidia; Butler, Tracy; Fieremans, Els; Axel, Leon; Rusinek, Henry; Nicholson, Charles; Zlokovic, Berislav V; Frangione, Blas; Blennow, Kaj; Ménard, Joël; Zetterberg, Henrik; Wisniewski, Thomas; de Leon, Mony J

    2015-08-01

    Accumulation of toxic protein aggregates-amyloid-β (Aβ) plaques and hyperphosphorylated tau tangles-is the pathological hallmark of Alzheimer disease (AD). Aβ accumulation has been hypothesized to result from an imbalance between Aβ production and clearance; indeed, Aβ clearance seems to be impaired in both early and late forms of AD. To develop efficient strategies to slow down or halt AD, it is critical to understand how Aβ is cleared from the brain. Extracellular Aβ deposits can be removed from the brain by various clearance systems, most importantly, transport across the blood-brain barrier. Findings from the past few years suggest that astroglial-mediated interstitial fluid (ISF) bulk flow, known as the glymphatic system, might contribute to a larger portion of extracellular Aβ (eAβ) clearance than previously thought. The meningeal lymphatic vessels, discovered in 2015, might provide another clearance route. Because these clearance systems act together to drive eAβ from the brain, any alteration to their function could contribute to AD. An understanding of Aβ clearance might provide strategies to reduce excess Aβ deposits and delay, or even prevent, disease onset. In this Review, we describe the clearance systems of the brain as they relate to proteins implicated in AD pathology, with the main focus on Aβ.

  2. The influence of body posture on lithium clearance

    DEFF Research Database (Denmark)

    Kamper, A L; Strandgaard, S; Holstein-Rathlou, N H;

    1988-01-01

    To establish appropriate standard circumstances for lithium clearance measurements, a study was undertaken in 12 healthy volunteers. In each subject, the glomerular filtration rate (GFR), as estimated by [51Cr]EDTA plasma clearance, and the renal clearances of lithium, sodium and potassium were...... measured four times at 1-week intervals: two in the supine and one in the sitting position, and one when the subject was walking around. Glomerular filtration rate was not influenced by posture changes. On the contrary, lithium clearance, which in the supine position was 30 +/- 9 ml/min (1 SD), tended...... to fall in the sitting position, and fell significantly to 26 +/- 5 ml/min (p less than 0.025) in walking subjects. Absolute proximal tubular reabsorption rate of fluid correspondingly rose from 83 +/- 16 to 92 +/- 15 ml/min (p less than 0.005) and sodium clearance fell from 1.52 +/- 0.81 to 1.00 +/- 0...

  3. Numerical simulation and optimization of clearance in sheet shearing process

    Institute of Scientific and Technical Information of China (English)

    秦泗吉; 李洪波; 彭加耕; 李硕本

    2003-01-01

    An analysis model to simplify the shearing and blanking process was developed. Based on the simplified model, the shearing process was simulated by FEM and analyzed for various clearances. An optimum clearance in the process was determined by new approach based on orientation of the maximum shearing stress on the characteristic line linking two blades, according to the law of crack propagation and experiments. The optimum clearance determined by this method can be used to dictate the range of reasonable clearance. By the new approach, the optimum clearance can be obtained conveniently and accurately even if there is some difference between the selected points, where the initial crack is assumed originated, and the actual one, where the initial crack occurs really.

  4. Neuroanatomy goes viral!

    Directory of Open Access Journals (Sweden)

    Jonathan eNassi

    2015-07-01

    Full Text Available The nervous system is complex not simply because of the enormous number of neurons it contains but by virtue of the specificity with which they are connected. Unraveling this specificity is the task of neuroanatomy. In this endeavor, neuroanatomists have traditionally exploited an impressive array of tools ranging from the Golgi method to electron microscopy. An ideal method for studying anatomy would label neurons that are interconnected, and, in addition, allow expression of foreign genes in these neurons. Fortuitously, nature has already partially developed such a method in the form of neurotropic viruses, which have evolved to deliver their genetic material between synaptically connected neurons while largely eluding glia and the immune system. While these characteristics make some of these viruses a threat to human health, simple modifications allow them to be used in controlled experimental settings, thus enabling neuroanatomists to trace multi-synaptic connections within and across brain regions. Wild-type neurotropic viruses, such as rabies and alpha-herpes virus, have already contributed greatly to our understanding of brain connectivity, and modern molecular techniques have enabled the construction of recombinant forms of these and other viruses. These newly engineered reagents are particularly useful, as they can target genetically defined populations of neurons, spread only one synapse to either inputs or outputs, and carry instructions by which the targeted neurons can be made to express exogenous proteins, such as calcium sensors or light-sensitive ion channels, that can be used to study neuronal function. In this review, we address these uniquely powerful features of the viruses already in the neuroanatomist's toolbox, as well as the aspects of their biology that currently limit their utility. Based on the latter, we consider strategies for improving viral tracing methods by reducing toxicity, improving control of transsynaptic

  5. Statistical mechanics of viral entry.

    Science.gov (United States)

    Zhang, Yaojun; Dudko, Olga K

    2015-01-09

    Viruses that have lipid-membrane envelopes infect cells by fusing with the cell membrane to release viral genes. Membrane fusion is known to be hindered by high kinetic barriers associated with drastic structural rearrangements-yet viral infection, which occurs by fusion, proceeds on remarkably short time scales. Here, we present a quantitative framework that captures the principles behind the invasion strategy shared by all enveloped viruses. The key to this strategy-ligand-triggered conformational changes in the viral proteins that pull the membranes together-is treated as a set of concurrent, bias field-induced activated rate processes. The framework results in analytical solutions for experimentally measurable characteristics of virus-cell fusion and enables us to express the efficiency of the viral strategy in quantitative terms. The predictive value of the theory is validated through simulations and illustrated through recent experimental data on influenza virus infection.

  6. Viral marketing as epidemiological model

    CERN Document Server

    Rodrigues, Helena Sofia

    2015-01-01

    In epidemiology, an epidemic is defined as the spread of an infectious disease to a large number of people in a given population within a short period of time. In the marketing context, a message is viral when it is broadly sent and received by the target market through person-to-person transmission. This specific marketing communication strategy is commonly referred as viral marketing. Due to this similarity between an epidemic and the viral marketing process and because the understanding of the critical factors to this communications strategy effectiveness remain largely unknown, the mathematical models in epidemiology are presented in this marketing specific field. In this paper, an epidemiological model SIR (Susceptible- Infected-Recovered) to study the effects of a viral marketing strategy is presented. It is made a comparison between the disease parameters and the marketing application, and simulations using the Matlab software are performed. Finally, some conclusions are given and their marketing impli...

  7. FastStats: Viral Hepatitis

    Science.gov (United States)

    ... Submit What's this? Submit Button NCHS Home Viral Hepatitis Recommend on Facebook Tweet Share Compartir Data are for the U.S. Morbidity Number of new hepatitis A cases: 1,781 (2013) Number of new ...

  8. Aseptic meningitis and viral myelitis.

    Science.gov (United States)

    Irani, David N

    2008-08-01

    Meningitis and myelitis represent common and very infrequent viral infections of the central nervous system, respectively. The number of cases of viral meningitis that occurs annually exceeds the total number of meningitis cases caused by all other etiologies combined. Focal central nervous system infections, such as occur in the spinal cord with viral myelitis, are much less common and may be confused with noninfectious disorders that cause acute flaccid paralysis. This article reviews some of the important clinical features, epidemiology, diagnostic approaches, and management strategies for patients with aseptic meningitis and viral myelitis. Particular focus is placed on the diseases caused by enteroviruses, which as a group account for most aseptic meningitis cases and many focal infections of the spinal cord.

  9. Microbiological diagnostics of viral hepatitis

    OpenAIRE

    HASDEMİR, Ufuk

    2016-01-01

    Viral hepatitis is an infection that primarily affects the liverbut may also have systemic clinical manifestations. The vastmajority of viral hepatitis are caused by one of five hepatotropicviruses: hepatitis A virus (HAV), hepatitis B virus (HBV),hepatitis C virus (HCV), hepatitis D (delta) virus (HDV), andhepatitis E virus (HEV) (Table I) [1]. HBV, HCV, and HDValso cause chronic hepatitis, whereas HAV does not. HEVcauses acute hepatitis in normal hosts but can cause protractedand chronic he...

  10. Food insecurity, CD4 counts, and incomplete viral suppression among HIV+ patients from Texas Children's Hospital: A pilot study

    Science.gov (United States)

    Our goal was to determine the relationship between food insecurity and CD4 counts and viral suppression among pediatric HIV-positive patients. Food insecurity was assessed by validated survey. CD4 counts and viral load were abstracted from patients’ charts. We used linear regression for the dependen...

  11. Viral RNAs are unusually compact.

    Directory of Open Access Journals (Sweden)

    Ajaykumar Gopal

    Full Text Available A majority of viruses are composed of long single-stranded genomic RNA molecules encapsulated by protein shells with diameters of just a few tens of nanometers. We examine the extent to which these viral RNAs have evolved to be physically compact molecules to facilitate encapsulation. Measurements of equal-length viral, non-viral, coding and non-coding RNAs show viral RNAs to have among the smallest sizes in solution, i.e., the highest gel-electrophoretic mobilities and the smallest hydrodynamic radii. Using graph-theoretical analyses we demonstrate that their sizes correlate with the compactness of branching patterns in predicted secondary structure ensembles. The density of branching is determined by the number and relative positions of 3-helix junctions, and is highly sensitive to the presence of rare higher-order junctions with 4 or more helices. Compact branching arises from a preponderance of base pairing between nucleotides close to each other in the primary sequence. The density of branching represents a degree of freedom optimized by viral RNA genomes in response to the evolutionary pressure to be packaged reliably. Several families of viruses are analyzed to delineate the effects of capsid geometry, size and charge stabilization on the selective pressure for RNA compactness. Compact branching has important implications for RNA folding and viral assembly.

  12. Effects of drugs on mucus clearance.

    Science.gov (United States)

    Houtmeyers, E; Gosselink, R; Gayan-Ramirez, G; Decramer, M

    1999-08-01

    Mucociliary clearance (MCC), the process in which airway mucus together with substances trapped within are moved out of the lungs, is an important defence mechanism of the human body. Drugs may alter this process, such that it is necessary to know the effect of the drugs on MCC. Indeed, agents stimulating MCC may be used therapeutically in respiratory medicine, especially in patients suspected of having an impairment of their mucociliary transport system. In contrast, caution should be taken with drugs depressing MCC as an undesired side-effect, independently of their therapeutic indication. Since cough clearance (CC) serves as a back-up system when MCC fails, the influence of drugs must be examined not only on MCC but also on CC. Ultimately, the clinical repercussions of alterations in mucus transport induced by drug administration must be studied. Tertiary ammonium compounds (anticholinergics), aspirin, anaesthetic agents and benzodiazepines have been shown to be capable of depressing the mucociliary transport system. Cholinergics, methylxanthines, sodium cromoglycate, hypertonic saline, saline as well as water aerosol have been shown to increase MCC. Adrenergic antagonists, guaifenesin, S-carboxymethylcysteine, sodium 2-mercapto-ethane sulphonate and frusemide have been reported not to alter the mucociliary transport significantly. Amiloride, uridine 5'-triphosphate (UTP), quaternary ammonium compounds (anticholinergics), adrenergic agonists, corticosteroids, recombinant human deoxyribonuclease (rhDNase), N-acetylcysteine, bromhexine and ambroxol have been reported either not to change or to augment MCC. Indirect data suggest that surfactant as well as antibiotics may improve the mucociliary transport system. As for the influence of drugs on CC, amiloride and rhDNase have been demonstrated to increase the effectiveness of cough. A trend towards an improved CC was noted after treatment with adrenergic agonists. The anticholinergic agent ipratropium bromide, which

  13. 64Cu loaded liposomes as positron emission tomography imaging agents

    DEFF Research Database (Denmark)

    Petersen, Anncatrine Luisa; Binderup, Tina; Rasmussen, Palle;

    2011-01-01

    We have developed a highly efficient method for utilizing liposomes as imaging agents for positron emission tomography (PET) giving high resolution images and allowing direct quantification of tissue distribution and blood clearance. Our approach is based on remote loading of a copper-radionuclid...

  14. Integrated Turbine Tip Clearance and Gas Turbine Engine Simulation

    Science.gov (United States)

    Chapman, Jeffryes W.; Kratz, Jonathan; Guo, Ten-Huei; Litt, Jonathan

    2016-01-01

    Gas turbine compressor and turbine blade tip clearance (i.e., the radial distance between the blade tip of an axial compressor or turbine and the containment structure) is a major contributing factor to gas path sealing, and can significantly affect engine efficiency and operational temperature. This paper details the creation of a generic but realistic high pressure turbine tip clearance model that may be used to facilitate active tip clearance control system research. This model uses a first principles approach to approximate thermal and mechanical deformations of the turbine system, taking into account the rotor, shroud, and blade tip components. Validation of the tip clearance model shows that the results are realistic and reflect values found in literature. In addition, this model has been integrated with a gas turbine engine simulation, creating a platform to explore engine performance as tip clearance is adjusted. Results from the integrated model explore the effects of tip clearance on engine operation and highlight advantages of tip clearance management.

  15. [Neuropsychiatric sequelae of viral meningitis in adults].

    Science.gov (United States)

    Damsgaard, Jesper; Hjerrild, Simon; Renvillard, Signe Groth; Leutscher, Peter Derek Christian

    2011-10-10

    Viral meningitis is considered to be a benign illness with only mild symptoms. In contrast to viral encephalitis and bacterial meningitis, the prognosis is usually good. However, retrospective studies have demonstrated that patients suffering from viral meningitis may experience cognitive impairment following the acute course of infection. Larger controlled studies are needed to elucidate the potential neuropsychiatric adverse outcome of viral meningitis.

  16. Impaired clearance of influenza A virus in obese, leptin receptor deficient mice is independent of leptin signaling in the lung epithelium and macrophages.

    Directory of Open Access Journals (Sweden)

    Kathryn A Radigan

    Full Text Available During the recent H1N1 outbreak, obese patients had worsened lung injury and increased mortality. We used a murine model of influenza A pneumonia to test the hypothesis that leptin receptor deficiency might explain the enhanced mortality in obese patients.We infected wild-type, obese mice globally deficient in the leptin receptor (db/db and non-obese mice with tissue specific deletion of the leptin receptor in the lung epithelium (SPC-Cre/LepR fl/fl or macrophages and alveolar type II cells (LysM-Cre/Lepr fl/fl with influenza A virus (A/WSN/33 [H1N1] (500 and 1500 pfu/mouse and measured mortality, viral clearance and several markers of lung injury severity.The clearance of influenza A virus from the lungs of mice was impaired in obese mice globally deficient in the leptin receptor (db/db compared to normal weight wild-type mice. In contrast, non-obese, SP-C-Cre+/+/LepR fl/fl and LysM-Cre+/+/LepR fl/fl had improved viral clearance after influenza A infection. In obese mice, mortality was increased compared with wild-type mice, while the SP-C-Cre+/+/LepR fl/fl and LysM-Cre+/+/LepR fl/fl mice exhibited improved survival.Global loss of the leptin receptor results in reduced viral clearance and worse outcomes following influenza A infection. These findings are not the result of the loss of leptin signaling in lung epithelial cells or macrophages. Our results suggest that factors associated with obesity or with leptin signaling in non-myeloid populations such as natural killer and T cells may be associated with worsened outcomes following influenza A infection.

  17. A comparative review of HLA associations with hepatitis B and C viral infections across global populations

    Institute of Scientific and Technical Information of China (English)

    Rashmi Singh; Rashmi Kaul; Anil Kaul; Khalid Khan

    2007-01-01

    Hepatitis B (HBV) and hepatitis C (HCV) viral infection or co-infection leads to risk of development of chronic infection, cirrhosis and hepatocellular carcinoma (HCC). Immigration and globalization have added to the challenges of public health concerns regarding chronic HBV and HCV infections worldwide. The aim of this study is to review existing global literature across ethnic populations on HBV and HCV related human leukocyte antigen (HLA) associations in relation to susceptibility, viral persistence and treatment. Extensive literature search was conducted to explore the HLA associations in HBV and HCV infections reported across global populations over the past decade to understand the knowledge status, weaknesses and strengths of this information in different ethnic populations. HLA DR13 is consistently associated with HBV clearance globally. HLADRB1*11/*12 alleles and DQB1*0301 are associated with HBV persistence but with HCV clearance worldwide. Consistent association of DRB1*03 and *07 is observed with HCV susceptibility and non-responsiveness to HBV vaccination across the population. HLA DR13 is protective for vertical HBV and HCV transmission in Chinese and Italian neonates, but different alleles are associated with their susceptibility in these populations. HLA class I molecule interactions with Killer cell immunoglobulin like receptors (KIR) of natural killer (NK) cells modulate HCV infection outcome via regulating immune regulatory cells and molecules. HLA associations with HBV vaccination, interferon therapy in HBV and HCV, and with extra hepatic manifestations of viral hepatitis are also discussed. Systematic studies in compliance with global regulatory standards are required to identify the HLA specific viral epitope, stage specific T cell populations interacting with different HLA alleles during disease progression and viral clearance ofchronic HBV or HCV infections among different ethnic populations. These studies would facilitate stage specific

  18. DNA-AuNP networks on cell membranes as a protective barrier to inhibit viral attachment, entry and budding.

    Science.gov (United States)

    Li, Chun Mei; Zheng, Lin Ling; Yang, Xiao Xi; Wan, Xiao Yan; Wu, Wen Bi; Zhen, Shu Jun; Li, Yuan Fang; Luo, Ling Fei; Huang, Cheng Zhi

    2016-01-01

    Viral infections have caused numerous diseases and deaths worldwide. Due to the emergence of new viruses and frequent virus variation, conventional antiviral strategies that directly target viral or cellular proteins are limited because of the specificity, drug resistance and rapid clearance from the human body. Therefore, developing safe and potent antiviral agents with activity against viral infection at multiple points in the viral life cycle remains a major challenge. In this report, we propose a new modality to inhibit viral infection by fabricating DNA conjugated gold nanoparticle (DNA-AuNP) networks on cell membranes as a protective barrier. The DNA-AuNPs networks were found, via a plaque formation assay and viral titers, to have potent antiviral ability and protect host cells from human respiratory syncytial virus (RSV). Confocal immunofluorescence image analysis showed 80 ± 3.8% of viral attachment, 91.1 ± 0.9% of viral entry and 87.9 ± 2.8% of viral budding were inhibited by the DNA-AuNP networks, which were further confirmed by real-time fluorescence imaging of the RSV infection process. The antiviral activity of the networks may be attributed to steric effects, the disruption of membrane glycoproteins and limited fusion of cell membrane bilayers, all of which play important roles in viral infection. Therefore, our results suggest that the DNA-AuNP networks have not only prophylactic effects to inhibit virus attachment and entry, but also therapeutic effects to inhibit viral budding and cell-to-cell spread. More importantly, this proof-of-principle study provides a pathway for the development of a universal, broad-spectrum antiviral therapy.

  19. [Pathology and viral metagenomics, a recent history].

    Science.gov (United States)

    Bernardo, Pauline; Albina, Emmanuel; Eloit, Marc; Roumagnac, Philippe

    2013-05-01

    Human, animal and plant viral diseases have greatly benefited from recent metagenomics developments. Viral metagenomics is a culture-independent approach used to investigate the complete viral genetic populations of a sample. During the last decade, metagenomics concepts and techniques that were first used by ecologists progressively spread into the scientific field of viral pathology. The sample, which was first for ecologists a fraction of ecosystem, became for pathologists an organism that hosts millions of microbes and viruses. This new approach, providing without a priori high resolution qualitative and quantitative data on the viral diversity, is now revolutionizing the way pathologists decipher viral diseases. This review describes the very last improvements of the high throughput next generation sequencing methods and discusses the applications of viral metagenomics in viral pathology, including discovery of novel viruses, viral surveillance and diagnostic, large-scale molecular epidemiology, and viral evolution.

  20. NUMERICAL SIMULATION OF TIP-CLEARANCE FLOW IN CASCADE

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    The tip-clearance flow in a cascade was numerically simulated by solving the RANS equations of incompressible fluids. The computational model was based upon the artificial compressibility formulation proposed by Chorin. The Baldwin-Lomax turbulence model was used to make the governing equations closed. For the specific structure of tip-clearance flow, a multi-block grid structure was adopted to facilitate numerical computations. The comparison of numerical results with experimental data indicates that the present method is capable of simulating tip-clearance flows with satisfactory accuracy.

  1. System-Level Design of a Shape Memory Alloy Actuator for Active Clearance Control in the High-Pressure Turbine

    Science.gov (United States)

    DeCastro, Jonathan A.; Melcher, Kevin J.; Noebe, Ronald D.

    2005-01-01

    This paper describes results of a numerical analysis evaluating the feasibility of high-temperature shape memory alloys (HTSMA) for active clearance control actuation in the high-pressure turbine section of a modern turbofan engine. The prototype actuator concept considered here consists of parallel HTSMA wires attached to the shroud that is located on the exterior of the turbine case. A transient model of an HTSMA actuator was used to evaluate active clearance control at various operating points in a test bed aircraft engine simulation. For the engine under consideration, each actuator must be designed to counteract loads from 380 to 2000 lbf and displace at least 0.033 inches. Design results show that an actuator comprised of 10 wires 2 inches in length is adequate for control at critical engine operating points and still exhibits acceptable failsafe operability and cycle life. A proportional-integral-derivative (PID) controller with integrator windup protection was implemented to control clearance amidst engine transients during a normal mission. Simulation results show that the control system exhibits minimal variability in clearance control performance across the operating envelope. The final actuator design is sufficiently small to fit within the limited space outside the high-pressure turbine case and is shown to consume only small amounts of bleed air to adequately regulate temperature.

  2. Iron load

    Directory of Open Access Journals (Sweden)

    Filippo Cassarà

    2013-03-01

    Full Text Available Recent research addressed the main role of hepcidin in the regulation of iron metabolism. However, while this mechanism could be relevant in causing iron load in Thalassemia Intermedia and Sickle-Cell Anemia, its role in Thalassemia Major (TM is marginal. This is mainly due to the high impact of transfusional requirement into the severe increase of body iron. Moreover, the damage of iron load may be worsened by infections, as HCV hepatitis, or liver and endocrinological damage. One of the most relevant associations was found between splenectomy and increase of risk for mortality due,probably, to more severe iron load. These issues suggest as morbidity and mortality of this group of patients they do not depend only by our ability in controlling heart damage but even in preventing or treating particular infections and complications. This finding is supported by the impairment of survival curves in patients with complications different from heart damage. However, because, during recent years different direct and indirect methods to detect iron overload in patients affected by secondary hemochromatosis have been implemented, our ability to maintain under control iron load is significantly improved. Anyway, the future in iron load management remains to be able to have an iron load map of our body for targeting chelation and other medical treatment according to the single organ damage.

  3. A three-dimensional model of tracheobronchial particle distribution during mucociliary clearance in the human respiratory tract.

    Science.gov (United States)

    Sturm, Robert

    2013-05-01

    Although theoretical approaches to tracheobronchial (TB) clearance have been continuously refined during the past decades, questions concerning the exact course of particle removal from the TB tree have been largely remained unsolved. In order to clarify this problem, three-dimensional patterns of mucociliary particle clearance have to be generated at pre-defined time points after particle exposure. Here, we present a mathematical method for the generation of respective clearance patterns. Three-dimensional transport paths of inhaled particles as well as spatial deposition patterns were generated by determining spatial information of all airway tubes passed by the particles and the particle deposition sites. Three-dimensional data were converted to a coordinate system, within which the trachea represented the z-axis. Visualization of stored data was realized with the help of a freely available program code that is specialized in processing huge data sets. Mucociliary clearance of deposited particular mass was computed by assuming (1) an interrelationship between mucus velocity and airway caliber and (2) an average tracheal mucus velocity of 5.5mm min(-1). Position of cleared particles within the spatial TB tree was determined at t=0 h (immediately after exposure), t=12 h and t=24 h. Spatial patterns of mucociliary clearance were computed for particles with a uniform geometric diameter of 5μm and a density of 1g cm(-3). Inhalation of the aerosol loaded with those particles took place under sitting breathing conditions (breathing frequency: 15min(-1), tidal volume: 750 ml). As demonstrated by the generated clearance patterns, mucociliary transport of 5μm particles is completed after 30 h. Within the first 12 h following aerosol exposure, about 75% of the initially deposited particular mass is removed from the TB tree. After 24 h, 95% of the particles have been cleared. Clearance patterns are characterized by a successive transition of maximal particle

  4. Discussing viral load levels after HIV/AIDS merges HBV/HCV infection and its relationship with T lymphocytes%HIV/AIDS合并HBV/HCV感染病毒载量水平及与T淋巴细胞相关性的探讨

    Institute of Scientific and Technical Information of China (English)

    张茹薏; 游晶; 杨微波; 饶少锋

    2016-01-01

    目的:探讨人类免疫缺陷病毒(HIV)/艾滋病(AIDS)合并乙型肝炎病毒(HBV)/丙型肝炎病毒(HCV)感染后病毒载量水平变化及对机体T淋巴细胞免疫机制的影响。方法分别测定 HIV/AIDS单纯感染组,HIV/HBV合并感染组,HIV/HCV合并感染组3组的 HIV RNA、HBV DNA、HCV RNA、CD4+ T淋巴细胞频数、CD8+ T淋巴细胞频数、CD4/CD8比值,并分析各组T淋巴细胞与HIV RNA的关系,HBV DNA/HCV RNA与HIV RNA、CD4+ T淋巴细胞、CD8+ T淋巴细胞、CD4/CD8比值的相关性。结果 HIV/AIDS单纯感染组、HIV/HBV合并感染组及 HIV/HCV合并感染组的CD4+ T 淋巴细胞与各自组的HIV RNA呈负相关,差异有统计学意义(P<0.05);HIV/AIDS单纯感染组、HIV/HBV合并感染组的CD8+ T淋巴细胞与各自组的HIV RNA呈负相关,差异有统计学意义(P<0.05);HIV/AIDS单纯感染组、HIV/HBV合并感染组及 HIV/HCV合并感染组的CD4/CD8与各自组的HIV RNA呈负相关,差异有统计学意义(P<0.05)。结论合并感染 HBV后,HIV/AIDS患者T细胞的数量下降更明显,致HIV RNA、HBV DNA高载量,加速了 HIV病情进展;感染 HBV后CD4+ T细胞的数量下降比感染HCV更明显。%Objective To explore the viral load levels after HIV/AIDS merges HBV/HCV infection and its relationship with T lymphocytes .Methods HIV RNA ,HBV DNA ,HCV RNA ,CD4+ T lymphocyte frequency ,CD8+ T lymphocyte frequency ,CD4/CD8 measured in HIV/AIDS simple infection group ,mixed HIV/HBV infection group and mixed HIV/HCV infection group .Ana‐lyze relationship of T lymphocyte and HIV RNA ,the correlation of HBV DNA/HCV RNA ,HIV RNA ,CD4+ T lymphocyte fre‐quency ,CD8+ T lymphocyte frequency ,CD4/CD8 .Results CD4+ T lymphocyte frequency of HIV/AIDS simple infection group , mixed HIV/HBV infection group and mixed HIV/HCV infection group showed negative correlated with their respective

  5. 低水平病毒载量长期不进展人类免疫缺陷病毒-1感染者的人类免疫缺陷病毒-1的遗传分析%Genetic analysis of human immunodeficieney virus-1 in long-term non-progress human immunodeficiency virus-1 infected individuals with low viral load

    Institute of Scientific and Technical Information of China (English)

    陈伟烈; 唐小平; 唐漾波; 魏绍静

    2009-01-01

    目的 分析低水平病毒载量长期不进展(LTNP)HIV-1感染者HIV-1的遗传特征.方法 采用有限稀释套式PCR、终点PCR和序列确证分析等技术对5例低病毒载量LTNP HIV-1感染者不同随访时间点HIV-1前病毒enw基因c2-v3-c3区域和gag基因p17区域进行扩增和序列分析.分别计算不同时间点内以及不同时间点与用于分析的最早时间点之间上述两个基因区域的基因多样性和基因离散率,依据基因离散率计算基因的进化率,统计学分析用GraphPad Prism 5软件.结果 5例患者在21个随访时间点共获得115条c2-v3-c3序列和173条p17序列.进化树分析表明,不同患者的序列分开,同一患者的序列特异地聚集,序列质量可靠.5例患者env基因c2-v3-c3区域不同时间点基因多样性为0~6.38%,平均为2.1%,病例1、3和5基因多样性随感染时间的增加逐渐升高(r=0.7257、0.4954、0.3288),病例2和4基因多样性随感染时间的增加逐渐下降(r=-0.3759、-0.5028);基因离散率为0.1%~6.5%,平均为2.9%,除病例1外,基因离散率均随感染时间间隔的增加逐渐升高,进化率分别为每年每位点-0.13%、0.81%、0.09%、0.14%和0.16%,平均为0.21%.gag基因p17区域基因多样性为0~2.5%,平均为1.2%,基因离散率为0.2%~2.7%,平均为1.4%,除病例3基因多样性和基因离散率随感染时间或时间间隔的增加下降外,其余病例均随感染时间或时间间隔的增加而逐渐升高,进化率分别为每年每位点0.087%、0.064%、-0.014%、0.081%和0.087%,平均为0.061%.结论 低水平病毒载量LTNP HIV-1感染者HIV-1有复制能力,病毒基因维持较低水平的进化;HIV-1 env基因变化的程度大于gag基因.%Objective To analyze the genetic characteristics of human immunodeficiency virus (HIV)-1 in long-term non-progress (LTNP) HIV-1 infected individuals with low viral load. Methods Limiting dilution nested polymerase chain reaction (PCR) and end-point PCR were used to

  6. Enterovirus 71-induced autophagy increases viral replication and pathogenesis in a suckling mouse model

    OpenAIRE

    Lee, Ying-Ray; Wang, Po-Shun; Wang, Jen-Ren; Liu, Hsiao-Sheng

    2014-01-01

    Background We previously reported that Enterovirus 71 (EV71) infection activates autophagy, which promotes viral replication both in vitro and in vivo. In the present study we further investigated whether EV71 infection of neuronal SK-N-SH cells induces an autophagic flux. Furthermore, the effects of autophagy on EV71-related pathogenesis and viral load were evaluated after intracranial inoculation of mouse-adapted EV71 (MP4 strain) into 6-day-old ICR suckling mice. Results We demonstrated th...

  7. 吲哚胺2,3双加氧酶与乙肝病毒不同感染状态T淋巴细胞亚群及病毒载量的相关性研究%Investigation of the correlation between indoleamine 2,3-dioxygenase and T cell subsets,viral load in different hepatitis B virus infection status

    Institute of Scientific and Technical Information of China (English)

    曾道炳; 卢实春; 李军峰; 胡冬; 周育森

    2012-01-01

    目的 探讨乙肝病毒(HBV)不同感染状态下,吲哚胺2,3双加氧酶(indoleamine 2,3-dioxygenase,IDO)表达水平及其与T淋巴细胞亚群及病毒载量的相关性.方法 检测受检者外周静脉血IDO mRNA、IDO蛋白、IDO活性,T淋巴细胞亚群及病毒载量(对照组除外);进行各组间均数比较及相关性分析.结果 IDO mRNA、IDO蛋白及IDO活性从高到低依次为急性乙型肝炎组(acute hepatitis B,AHB)、肝硬化组(HBV-related liver cirrhosis,LC)、慢性乙型肝炎组(chronic hepatitis B,CHB)、肝癌组(HBV-related hepatocellular carci