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Sample records for clearance viral load

  1. 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

    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...

  2. 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

    , respectively. A greater HCV RNA level was associated with a greater chance of being infected with HCV genotype 1 (aOR, 1.60 per 1 log higher [95% CI, 1.36-1.88]). CONCLUSIONS: More than three-quarters of the HIV- and HCV Ab-positive patients in EuroSIDA showed active HCV replication. Viremia was more frequent......BACKGROUND: Variables influencing serum hepatitis C virus (HCV) RNA levels and genotype distribution in individuals with human immunodeficiency virus (HIV) infection are not well known, nor are factors determining spontaneous clearance after exposure to HCV in this population. METHODS: All HCV...... antibody (Ab)-positive patients with HIV infection in the EuroSIDA cohort who had stored samples were tested for serum HCV RNA, and HCV genotyping was done for subjects with viremia. Logistic regression was used to identify variables associated with spontaneous HCV clearance and HCV genotype 1. RESULTS: Of...

  3. Effect of Internal Clearance on Load Distribution and Life of Radially Loaded Ball and Roller Bearings

    Science.gov (United States)

    Oswald, Fred B.; Zaretsky, Erwin V.; Poplawski, Joseph V.

    2012-01-01

    The effect of internal clearance on radially loaded deepgroove ball and cylindrical roller bearing load distribution and fatigue life was determined for four clearance groups defined in the bearing standards. The analysis was extended to negative clearance (interference) conditions to produce a curve of life factor versus internal clearance. Rolling-element loads can be optimized and bearing life maximized for a small negative operating clearance. Life declines gradually with positive clearance and rapidly with increasing negative clearance. Relationships were found between bearing life and internal clearance as a function of ball or roller diameter, adjusted for load. Results are presented as life factors for radially loaded bearings independent of bearing size or applied load. In addition, a modified Stribeck Equation is presented that relates the maximum rolling-element load to internal bearing clearance.

  4. A trend towards increasing viral load in newly diagnosed HIV-infected inpatients in southeast China.

    Science.gov (United States)

    Chen, Y; Wang, Z; Huang, A; Yuan, J; Wei, D; Ye, H

    2016-06-01

    Peripheral blood viral load is an important indicator of viral production and clearance. Previous studies have suggested that viral load might predict the rate of decrease in CD4+ cell count and progression to AIDS and death. Here, we conducted a retrospective analysis of the trends in HIV-1 viral load in southeast China. Among inpatients newly diagnosed with HIV infection, we found that viral load has increased over the past decade from 4·20 log10 copies/ml in 2002 to 6·61 log10 copies/ml in 2014, with a mean increase of 0·19 log10 copies/ml each year. However, the CD4+ cell count was stable and insensitive to changes in viral load. Thus, increasing viral load appears to be an emerging trend in newly diagnosed HIV-infected inpatients. PMID:26732896

  5. 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. PMID:27589232

  6. Fecal Viral Load and Norovirus-associated Gastroenteritis

    OpenAIRE

    Martin C W Chan; Sung, Joseph J Y; Lam, Rebecca K. Y.; Chan, Paul K.S.; Nelson L S Lee; Lai, Raymond W.M.; Leung, Wai K

    2006-01-01

    We report the median cDNA viral load of norovirus genogroup II is >100-fold higher than that of genogroup I in the fecal specimens of patients with norovirus-associated gastroenteritis. We speculate that increased cDNA viral load accounts for the higher transmissibility of genogroup II strains through the fecal-oral route.

  7. 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. PMID:26087934

  8. Natural FCoV infection: cats with FIP exhibit significantly higher viral loads than healthy infected cats.

    Science.gov (United States)

    Kipar, Anja; Baptiste, Keith; Barth, Andreas; Reinacher, Manfred

    2006-02-01

    Natural feline coronavirus (FCoV) infection has been shown to not only induce intestinal infection with viral shedding, but also systemic infection which either remains without clinical signs or leads to feline infectious peritonitis (FIP). As systemic infection is not the key event in the development of FIP, the question arises as to whether a potential difference in viral load might be of importance. Therefore, the purpose of this study was to quantitatively assess feline coronavirus (FCoV) RNA loads in haemolymphatic tissues of healthy, long-term FCoV-infected cats and cats with FIP. In cats that died from FIP, viral loads were significantly higher, indicating a higher rate of viral replication or a reduced capacity for viral clearance in cats developing and/or suffering from FIP. PMID:16213766

  9. HIV-1 viral diversity and its implications for viral load testing: review of current platforms.

    Science.gov (United States)

    Luft, LeeAnne M; Gill, M John; Church, Deirdre L

    2011-10-01

    The 2008 Recommendations for care of the International AIDS Society reaffirmed the importance of both accurate and sensitive viral load assessment, and by necessity, access to viral load assays. HIV-1 viral load testing is considered essential when initiating antiretroviral therapy (ART), when monitoring ART response, and when considering switching ART regimens. The demand for accurate, reproducible, and cost-effective viral load assays is therefore a global issue. Although the North American and Western European experience has historically been with HIV-1 group M subtype B virus, this paradigm is changing rapidly as migrants and refugees from developing countries with non-B subtype infections often now present for care in the developed world, and travelers to developing countries acquire non-B subtype infection abroad and present for care at home. Awareness of any clinical or laboratory differences between the common HIV-1 group M subtype B and the newer HIV-1 strains being seen in practice is therefore increasingly important. This review of current HIV-1 viral load testing is focused on the potential value of a standardized genotype assignment for HIV-1 viral subtypes, regular monitoring of the performance of available commercial HIV viral load assays on emerging non-B HIV subtypes, circulating recombinant forms (CRFs) and unique recombinant forms (URFs), and a discussion of the implications for resource-limited settings. PMID:21767972

  10. 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.

  11. Initial viral load and the outcomes of SARS

    Science.gov (United States)

    Chu, Chung-Ming; Poon, Leo L.M.; Cheng, Vincent C.C.; Chan, Kin-Sang; Hung, Ivan F.N.; Wong, Maureen M.L.; Chan, Kwok-Hung; Leung, Wah-Shing; Tang, Bone S.F.; Chan, Veronica L.; Ng, Woon-Leung; Sim, Tiong-Chee; Ng, Ping-Wing; Law, Kin-Ip; Tse, Doris M.W.; Peiris, Joseph S.M.; Yuen, Kwok-Yung

    2004-01-01

    Background Severe acute respiratory syndrome (SARS) is caused by a novel coronavirus. It may progress to respiratory failure, and a significant proportion of patients die. Preliminary data suggest that a high viral load of the SARS coronavirus is associated with adverse outcomes in the intensive care unit, but the relation of viral load to survival is unclear. Methods We prospectively studied an inception cohort of 133 patients with virologically confirmed SARS who were admitted to 2 general acute care hospitals in Hong Kong from Mar. 24 to May 4, 2003. The patients were followed until death or for a minimum of 90 days. We used Cox proportional hazard modelling to analyze potential predictors of survival recorded at the time of presentation, including viral load from nasopharyngeal specimens (measured by quantitative reverse transcriptase polymerase chain reaction [PCR] of the SARS-associated coronavirus). Results Thirty-two patients (24.1%) met the criteria for acute respiratory distress syndrome, and 24 patients (18.0%) died. The following baseline factors were independently associated with worse survival: older age (61–80 years) (adjusted hazard ratio [HR] 5.24, 95% confidence interval [CI] 2.03–13.53), presence of an active comorbid condition (adjusted HR 3.36, 95% CI 1.44–7.82) and higher initial viral load of SARS coronavirus, according to quantitative PCR of nasopharyngeal specimens (adjusted HR 1.21 per log10 increase in number of RNA copies per millilitre, 95% CI 1.06–1.39). Interpretation We found preliminary evidence that higher initial viral load is independently associated with worse prognosis in SARS. Mortality data for patients with SARS should be interpreted in light of age, comorbidity and viral load. These considerations will be important in future studies of SARS. PMID:15557587

  12. 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.

  13. Targeting CD45RB alters T cell migration and delays viral clearance.

    Science.gov (United States)

    Lim, Bock; Sutherland, Robyn M; Zhan, Yifan; Deliyannis, Georgia; Brown, Lorena E; Lew, Andrew M

    2006-02-01

    CD45 is a receptor tyrosine phosphatase essential for TCR signaling. One isoform, CD45RB, is down-regulated in memory cells and targeting CD45RB with a specific antibody has been shown to inhibit graft rejection. Its role in immunity to infection, however, has not been tested. Here, we report the effect of anti-CD45RB antibody treatment on the induction of anti-influenza CD8+ T cells and viral clearance. Anti-CD45RB-treated mice had delayed pulmonary viral clearance compared with untreated mice whose infection was completely cleared by day 8 post-infection. In anti-CD45RB-treated mice, the total CD4+ and CD8+ T cell numbers in both the lungs and mediastinal nodes were substantially reduced at days 5 and 8; this effect was less marked for the spleen. CD8+ T cells specific for influenza virus were also reduced compared with the control group in all three organs at day 8. By day 11, when both treated and control groups showed no virus remaining in the lungs, specific CD8+ T cell numbers were at similar low levels. Homing to lymph nodes and lung of dye-labeled T cells was greatly inhibited (by >80%) by anti-CD45RB treatment. This reduced homing corresponded with reduced CD62L and beta1-integrin expression in both uninfected and infected mice. Since CD62L plays a critical role in homing lymphocytes to lymph nodes, and high levels of CD62L and alpha4beta1-integrin are expressed by lymphocytes that home to bronchus-associated lymphoid tissue, we suggest that reduced expression of these molecules is a key explanation for the delay in immune responses. PMID:16361310

  14. Viral Load Monitoring of Antiretroviral Therapy, cohort viral load and HIV transmission in Southern Africa: A Mathematical Modelling Analysis

    OpenAIRE

    Estill, Janne; Aubrière, Cindy; Egger, Matthias; Johnson, Leigh; Wood, Robin; Garone, Daniela; Gsponer, Thomas; Wandeler, Gilles; Boulle, Andrew; Davies, Mary-Ann; Hallett, Timothy B.; Keiser, Olivia

    2012-01-01

    In low-income settings, treatment failure is often identified using CD4 cell count monitoring. Consequently, patients remain on a failing regimen, resulting in a higher risk of transmission. We investigated the benefit of routine viral load monitoring for reducing HIV transmission.

  15. Hepatic transcriptome analysis of hepatitis C virus infection in chimpanzees defines unique gene expression patterns associated with viral clearance.

    Directory of Open Access Journals (Sweden)

    Santosh Nanda

    Full Text Available Hepatitis C virus infection leads to a high rate of chronicity. Mechanisms of viral clearance and persistence are still poorly understood. In this study, hepatic gene expression analysis was performed to identify any molecular signature associated with the outcome of hepatitis C virus (HCV infection in chimpanzees. Acutely HCV-infected chimpanzees with self-limited infection or progression to chronicity were studied. Interferon stimulated genes were induced irrespective of the outcome of infection. Early induction of a set of genes associated with cell proliferation and immune activation was associated with subsequent viral clearance. Specifically, two of the genes: interleukin binding factor 3 (ILF3 and cytotoxic granule-associated RNA binding protein (TIA1, associated with robust T-cell response, were highly induced early in chimpanzees with self-limited infection. Up-regulation of genes associated with CD8+ T cell response was evident only during the clearance phase of the acute self-limited infection. The induction of these genes may represent an initial response of cellular injury and proliferation that successfully translates to a "danger signal" leading to induction of adaptive immunity to control viral infection. This primary difference in hepatic gene expression between self-limited and chronic infections supports the concept that successful activation of HCV-specific T-cell response is critical in clearance of acute HCV infection.

  16. 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.

  17. Psychiatric Distress, Drug Use, and HIV Viral Load Suppression in Russia.

    Science.gov (United States)

    Ustinov, A; Suvorova, A; Belyakov, A; Makhamatova, A; Levina, O; Krupitsky, E; Lioznov, D; Niccolai, L; Heimer, R

    2016-08-01

    To explore the influence of psychiatric distress and substance use on viral load suppression in HIV-infected patients taking ART we analyzed socio-demographic characteristics, CD4+ cells count and viral loads, the Symptom Check List-90 and the Addiction Severity Index of 75 patients who had taken ART for at least 6 month. Using viral load data as the marker of ART success, we divided the sample into two groups. Comparison of the groups showed that education, marriage, and female gender are predictors of optimal viral load suppression. Overall results failed to demonstrate substance use and psychiatric distress as predictors of viral load suppression. PMID:26809193

  18. 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

  19. Effect of the clearance and interference-fit on failure of the pin-loaded composites

    International Nuclear Information System (INIS)

    The aim of this study is to examine the effect of the clearance and interference-fit on the failure mode, failure load and bearing strength of the pin-loaded joints subjected to traction forces. The failure load and failure mode are determined both experimentally and numerically. Three-dimensional finite element models are created using ANSYS software. Non-linear contact analyses are performed to examine the effects of the clearance and interference for different ratios of the edge distance-to-hole diameter (E/D) and plate width-to-hole diameter (W/D). Damage is also examined using scanning electron microscope (SEM). It is observed that interference for all pin-loaded joint configurations is beneficial. A good agreement between experimental and numerical results is obtained.

  20. Multilaboratory Comparison of Hepatitis C Virus Viral Load Assays

    OpenAIRE

    Caliendo, A M; Valsamakis, A.; Zhou, Y.; Yen-Lieberman, B; Andersen, J; Young, S.; Ferreira-Gonzalez, A; Tsongalis, G. J.; Pyles, R.; Bremer, J W; Lurain, N. S.

    2006-01-01

    We report a multilaboratory evaluation of hepatitis C virus (HCV) viral load assays to determine their linear range, reproducibility, subtype detection, and agreement. A panel of HCV RNA samples ranging in nominal concentration from 1.0 to 7.0 log10 IU/ml was constructed by diluting a clinical specimen (genotype 1b). Replicates of the panel were tested in multiple laboratories using the Abbott TaqMan analyte-specific reagent (Abbott reverse transcription-PCR [RT-PCR]), Roche TaqMan RUO (Roche...

  1. Cutaneous human papillomavirus 88: Remarkable differences in viral load

    OpenAIRE

    Kullander, Johanna; Handisurya, Alessandra; Forslund, Ola; Geusau, Alexandra; Kirnbauer, Reinhard; Dillner, Joakim

    2008-01-01

    A human papillomavirus (HPV) was cloned from a patient with multiple squamous cell carcinomas (SCCs) and identified as HPV88, recently categorized into a new species within the genus Gamma. The HPV88 viral load in an SCC of the index patient exceeded 1 million copies/cell. By contrast, a survey of 447 skin lesions (79 actinic keratoses, 73 seborrhoeic keratoses, 169 basal cell carcinomas and 126 SCCs) and 362 healthy skin biopsies found detectable HPV88 DNA in only 7 specimens. All these had ...

  2. In vitro Evaluation of Biofield Treatment on Viral Load Against Human Immunodeficiency-1 and Cytomegalo Viruses

    OpenAIRE

    Trivedi, Mahendra Kumar

    2015-01-01

    Viral load quantification is the amount of particular viral DNA or RNA in a blood samples. It is one of the surrogate biomarker of AIDS. High viral load indicates that the immune system is failed to fight against viruses. The aim of this study was to evaluate the impact of biofield treatment on HIV-1 and HCMV in terms of viral loads as surrogate marker. The viral load assay was performed on stored stock cultures of HIV infected human plasma samples before and after 7 days of biofield treatmen...

  3. Stress analysis method for clearance-fit joints with bearing-bypass loads

    Science.gov (United States)

    Naik, R. A.; Crews, J. H., Jr.

    1989-01-01

    Within a multi-fastener joint, fastener holes may be subjected to the combined effects of bearing loads and loads that bypass the hole to be reacted elsewhere in the joint. The analysis of a joint subjected to search combined bearing and bypass loads is complicated by the usual clearance between the hole and the fastener. A simple analysis method for such clearance-fit joints subjected to bearing-bypass loading has been developed in the present study. It uses an inverse formulation with a linear elastic finite-element analysis. Conditions along the bolt-hole contact arc are specified by displacement constraint equations. The present method is simple to apply and can be implemented with most general purpose finite-element programs since it does not use complicated iterative-incremental procedures. The method was used to study the effects of bearing-bypass loading on bolt-hole contact angles and local stresses. In this study, a rigid, frictionless bolt was used with a plate having the properties of a quasi-isotropic graphite/epoxy laminate. Results showed that the contact angle as well as the peak stresses around the hole and their locations were strongly influenced by the ratio of bearing and bypass loads. For single contact, tension and compression bearing-bypass loading had opposite effects on the contact angle. For some compressive bearing-bypass loads, the hole tended to close on the fastener leading to dual contact. It was shown that dual contact reduces the stress concentration at the fastener and would, therefore, increase joint strength in compression. The results illustrate the general importance of accounting for bolt-hole clearance and contact to accurately compute local bolt-hole stresses for combined bearings and bypass loading.

  4. 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. PMID:27136459

  5. 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.

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

    DEFF Research Database (Denmark)

    Phillips, Andrew; Shroufi, Amir; Vojnov, Lara;

    2015-01-01

    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.......) 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...

  7. Increased alpha-9 human papillomavirus species viral load in human immunodeficiency virus positive women

    OpenAIRE

    Mbulawa, Zizipho Z. A.; Johnson, Leigh F.; Marais, Dianne J.; Gustavsson, Inger; Moodley, Jennifer R; Coetzee, David; Gyllensten, Ulf; Williamson, Anna-Lise

    2014-01-01

    Background: Persistent high-risk (HR) human papillomavirus (HPV) infection and increased HR-HPV viral load are associated with the development of cancer. This study investigated the effect of human immunodeficiency virus (HIV) co-infection, HIV viral load and CD4 count on the HR-HPV viral load; and also investigated the predictors of cervical abnormalities. Methods: Participants were 292 HIV-negative and 258 HIV-positive women. HR-HPV viral loads in cervical cells were determined by the real-...

  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. 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.

  10. Female sex and IL28B, a synergism for spontaneous viral clearance in hepatitis C virus (HCV seroconverters from a community-based cohort.

    Directory of Open Access Journals (Sweden)

    Charlotte H B S van den Berg

    Full Text Available BACKGROUND & AIMS: Since acute hepatitis C virus (HCV infection is often asymptomatic, it is difficult to examine the rate and determinants of spontaneous clearance. Consequently, these studies are subject to bias, which can potentially lead to biased rates of viral clearance and risk estimates. We evaluated determinants of spontaneous HCV clearance among HCV seroconverters identified in a unique community-based cohort. METHODS: Subjects were 106 drug users with documented dates of HCV seroconversion from the Amsterdam Cohort Study. Logistic regression was used to examine sociodemographic, behavioral, clinical, viral and host determinants, measured around acute infection, of HCV clearance. RESULTS: The spontaneous viral clearance rate was 33.0% (95% confidence interval (CI 24.2-42.8. In univariate analyses female sex and fever were significantly associated with spontaneous clearance. The favorable genotypes for rs12979860 (CC and rs8099917 (TT were associated with spontaneous clearance, although borderline significant. In multivariate analysis, females with the favorable genotype for rs12979860 (CC had an increased odds to spontaneously clear HCV infection (adjusted OR 6.62, 95% 2.69-26.13, whereas females with the unfavorable genotype were as likely as men with the favorable and unfavorable genotype to clear HCV. Chronic Hepatitis B infection and absence of HIV coinfection around HCV seroconversion also favor HCV clearance. CONCLUSIONS: This study shows that co-infection with HIV and HBV and genetic variation in the IL28B region play an important role in spontaneous clearance of HCV. Our findings suggest a possible synergistic interaction between female sex and IL28B in spontaneous clearance of HCV.

  11. Expression of suppressor of cytokine signaling 1 (SOCS1 impairs viral clearance and exacerbates lung injury during influenza infection.

    Directory of Open Access Journals (Sweden)

    Keer Sun

    2014-12-01

    Full Text Available Suppressor of cytokine signaling (SOCS proteins are inducible feedback inhibitors of cytokine signaling. SOCS1-/- mice die within three weeks postnatally due to IFN-γ-induced hyperinflammation. Since it is well established that IFN-γ is dispensable for protection against influenza infection, we generated SOCS1-/-IFN-γ-/- mice to determine whether SOCS1 regulates antiviral immunity in vivo. Here we show that SOCS1-/-IFN-γ-/- mice exhibited significantly enhanced resistance to influenza infection, as evidenced by improved viral clearance, attenuated acute lung damage, and consequently increased survival rates compared to either IFN-γ-/- or WT animals. Enhanced viral clearance in SOCS1-/-IFN-γ-/- mice coincided with a rapid onset of adaptive immune responses during acute infection, while their reduced lung injury was associated with decreased inflammatory cell infiltration at the resolution phase of infection. We further determined the contribution of SOCS1-deficient T cells to antiviral immunity. Anti-CD4 antibody treatment of SOCS1-/-IFN-γ-/- mice had no significant effect on their enhanced resistance to influenza infection, while CD8+ splenocytes from SOCS1-/-IFN-γ-/- mice were sufficient to rescue RAG1-/- animals from an otherwise lethal infection. Surprisingly, despite their markedly reduced viral burdens, RAG1-/- mice reconstituted with SOCS1-/-IFN-γ-/- adaptive immune cells failed to ameliorate influenza-induced lung injury. In conclusion, in the absence of IFN-γ, the cytoplasmic protein SOCS1 not only inhibits adaptive antiviral immune responses but also exacerbates inflammatory lung damage. Importantly, these detrimental effects of SOCS1 are conveyed through discrete cell populations. Specifically, while SOCS1 expression in adaptive immune cells is sufficient to inhibit antiviral immunity, SOCS1 in innate/stromal cells is responsible for aggravated lung injury.

  12. Evaluation of Biofield Modality on Viral Load of Hepatitis B and C Viruses

    OpenAIRE

    Trivedi, Mahendra Kumar

    2015-01-01

    Study background: Nowadays, hepatitis is a major challenge for clinical research, regulatory bodies, and clinicians who are trying to assess the more effectiveness of antiviral therapy against patients. Viral load count is the amount of particular viral DNA or RNA in a blood samples. It is one of the surrogate biomarker of hepatitis. High viral load indicates that the immune system is failed to fight against viruses. The aim of this study was to evaluate the impact of biofield modality o...

  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. PMID:26995036

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

    OpenAIRE

    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 occu...

  15. 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.

  16. Decreases in Community Viral Load Are Accompanied by Reductions in New HIV Infections in San Francisco

    OpenAIRE

    Moupali Das; Priscilla Lee Chu; Glenn-Milo Santos; Susan Scheer; Eric Vittinghoff; Willi McFarland; Grant N Colfax

    2010-01-01

    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. METHOD...

  17. Scale-up of HIV Viral Load Monitoring--Seven Sub-Saharan African Countries.

    Science.gov (United States)

    Lecher, Shirley; Ellenberger, Dennis; Kim, Andrea A; Fonjungo, Peter N; Agolory, Simon; Borget, Marie Yolande; Broyles, Laura; Carmona, Sergio; Chipungu, Geoffrey; De Cock, Kevin M; Deyde, Varough; Downer, Marie; Gupta, Sundeep; Kaplan, Jonathan E; Kiyaga, Charles; Knight, Nancy; MacLeod, William; Makumbi, Boniface; Muttai, Hellen; Mwangi, Christina; Mwangi, Jane W; Mwasekaga, Michael; Ng'Ang'A, Lucy W; Pillay, Yogan; Sarr, Abdoulaye; Sawadogo, Souleymane; Singer, Daniel; Stevens, Wendy; Toure, Christiane Adje; Nkengasong, John

    2015-11-27

    To achieve global targets for universal treatment set forth by the Joint United Nations Programme on human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) (UNAIDS), viral load monitoring for HIV-infected persons receiving antiretroviral therapy (ART) must become the standard of care in low- and middle-income countries (LMIC) (1). CDC and other U.S. government agencies, as part of the President's Emergency Plan for AIDS Relief, are supporting multiple countries in sub-Saharan Africa to change from the use of CD4 cell counts for monitoring of clinical response to ART to the use of viral load monitoring, which is the standard of care in developed countries. Viral load monitoring is the preferred method for immunologic monitoring because it enables earlier and more accurate detection of treatment failure before immunologic decline. This report highlights the initial successes and challenges of viral load monitoring in seven countries that have chosen to scale up viral load testing as a national monitoring strategy for patients on ART in response to World Health Organization (WHO) recommendations. Countries initiating viral load scale-up in 2014 observed increases in coverage after scale-up, and countries initiating in 2015 are anticipating similar trends. However, in six of the seven countries, viral load testing coverage in 2015 remained below target levels. Inefficient specimen transport, need for training, delays in procurement and distribution, and limited financial resources to support scale-up hindered progress. Country commitment and effective partnerships are essential to address the financial, operational, technical, and policy challenges of the rising demand for viral load monitoring. PMID:26605986

  18. Sequence elements correlating with circulating viral load in genotype 1b hepatitis C virus infection

    International Nuclear Information System (INIS)

    The correlation between hepatitis C virus (HCV) genomic sequences and circulating HCV RNA levels was assessed to investigate the genetic elements affecting viral load. The interferon sensitivity-determining region (ISDR) sequence and the serum viral load were strongly correlated in 226 patients examined. Analysis of the entire HCV genome from six patients (three with a high and the others with a low viral load) with similar ISDR sequences identified several candidate residues associated with viral load. The amino acid (aa) sequences of these candidate residues and flanking regions in 67 additional patients revealed that only the residue at aa 962 varied significantly between the HCV patients with low and high serum loads (P 0.042). At this position, alanine was observed more frequently in the patients with a high viral load. In conclusion, our results strongly suggest that serum HCV RNA loads are inversely correlated with amino acid substitutions in the ISDR, and aa 962 was identified as a possible second determinant of serum HCV RNA load

  19. 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.

  20. Viral load and clinicopathological features of chronic hepatitis C (1b) in a homogeneous patient population.

    Science.gov (United States)

    Fanning, L; Kenny, E; Sheehan, M; Cannon, B; Whelton, M; O'Connell, J; Collins, J K; Shanahan, F

    1999-03-01

    Monitoring the progression of hepatitis C virus (HCV) includes clinical, biochemical, and histological parameters. Quantitation of viral load by reverse-transcription polymerase chain reaction (RT-PCR) may offer a more reliable marker of disease status. Conflicting reports on viral titers may reflect heterogeneity of patient population, mode of infection, and viral type/subtype. The aim of this study was to correlate quantitative serum viral load with alanine transaminase (ALT) and histological status in a homogenous population. The study population consisted of 77 Rhesus-negative women with chronic hepatitis C type 1b. Homogenous features of this study population included: same defined source of infection (contaminated anti-D immunoglobulin); same duration of disease (17 years at the time of study); same viral type/subtype; same ethnic origin; all healthy child-bearing females at the time of infection; and an absence of competing risk factors for infectious and other liver diseases. None of the patients had received antiviral treatment at the time of study. Liver biopsy was performed on all patients. All biopsies were scored by a single histopathologist who was blinded to the clinical and viral status of each patient. A weak, but statistically significant, correlation (rs =.26; P <.05) between serum viral load and the degree of inflammation (mean value: 3.87 +/- 2.17 [SD]) was found. There was no significant correlation between serum viral load and the degree of fibrosis (mean value: 0.84 +/- 0.8 [SD]; P =.06). There was no significant correlation between serum viral load and ALT, although there was a correlation between ALT and the degree of inflammation (rs =.241; P =.035). PMID:10051496

  1. Viral Load of Human Herpesvirus 8 in Peripheral Blood of Human Immunodeficiency Virus-Infected Patients with Kaposi's Sarcoma

    OpenAIRE

    Tedeschi, Rosamaria; Enbom, Malin; Bidoli, Ettore; Linde, Annika; De Paoli, Paolo; Dillner, Joakim

    2001-01-01

    Viral load is an important marker of activity of viral diseases for a number of viruses. We wished to evaluate whether the viral load of human herpesvirus 8 (HHV-8) in peripheral blood was a consistent feature of Kaposi's sarcoma (KS) patients and whether the viral load correlated with human immunodeficiency virus (HIV) RNA levels, CD4 counts, and/or the HHV-8 seroreactivity. Fifty-four consecutive plasma samples from 14 patients with KS were evaluated for HHV-8 viral load by quantitative rea...

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

    Directory of Open Access Journals (Sweden)

    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

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

    Directory of Open Access Journals (Sweden)

    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.

  4. 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.

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

    International Nuclear Information System (INIS)

    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

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

    Directory of Open Access Journals (Sweden)

    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.

  7. 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.

  8. Human Papillomavirus prevalence, viral load and cervical intraepithelial neoplasia in HIV-infected women

    Directory of Open Access Journals (Sweden)

    Levi José E.

    2002-01-01

    Full Text Available HIV-infected women from São Paulo city were enrolled in a cross-sectional study on Human Papillomavirus (HPV and cervical intraepithelial neoplasia (CIN prevalence and their association with laboratory markers of AIDS, namely HIV viral load and CD4+ cell counts. A cervical specimen was collected and submitted to Hybrid Capture, a test for HPV viral load determination. HPV-DNA was detected in 173 of 265 women (64.5%. Twenty (7.5% women were infected by one or more low-risk viruses, 89 (33% by one or more high-risk viruses, and 64 (24% harbored at least one HPV type from each risk group. Abnormal smears were observed in 19% of the patients, though there were no invasive carcinomas. Severely immunosuppressed patients (CD4/µL <100 were at the greatest risk of having a cytological abnormality and a high high-risk HPV viral load.

  9. Viral load profiles in drug users with asymptomatic HIV infection and normal CD4 cell counts

    OpenAIRE

    Zubairi Djoerban

    2002-01-01

    Since the year 2000 there has been a steep increased in the number of HIV/AIDS patients in Indonesia, coming mostly from intravenous drug users. Antiretroviral treatment has been proved to decrease mortality and increase quality of life of HIV/AIDS patients. The treatment is given according to clinical condition of the patients, number of CD4 and viral load. In this study, CD4 and viral load were examined in 71 asymptomatic HIV patients originated from injecting-drug users. CD4 counting was p...

  10. Assessment of antiretroviral therapy by plasma viral load testing: standard and ICD HIV-1 p24 antigen and viral RNA (QC-PCR) assays compared.

    Science.gov (United States)

    Kappes, J C; Saag, M S; Shaw, G M; Hahn, B H; Chopra, P; Chen, S; Emini, E A; McFarland, R; Yang, L C; Piatak, M

    1995-10-01

    To assess the utility of quantitative competitive-polymerase chain reaction (QC-PCR) measurements of plasma human immunodeficiency virus type 1 (HIV-1) RNA and other viral load markers for assessment of antiretroviral therapy, we used archived cryopreserved specimens from a randomized controlled clinical trial of 135 patients (CD4+ T cell count or = 30 pg/ml) in 42% and 56%, respectively. All viral load parameters showed significant decreases from baseline within 1 week of initiation of zidovudine, as measured by standard p24 antigen assay, ICD p24 assay, and QC-PCR. At 1 week, patients treated with either 300 or 1,000 mg/day of L-697,661 showed significant decreases from baseline in plasma standard and ICD p24 antigen and QC-PCR-determined HIV-1 RNA levels. Whereas viral load decreases seen with zidovudine were sustained for the duration of treatment, plasma viral markers often returned to pretreatment levels despite ongoing L-697,661 treatment, with evidence of the emergence of drug-resistant virus. Whereas standard p24, ICD p24, and viral RNA levels changed similarly in response to treatment, the superior sensitivity and available dynamic range of plasma viral RNA assays like QC-PCR analysis provide an advantage for clinical monitoring of plasma viral load, allowing tracking of treatment-related changes even in patients with earlier stage disease and lower levels of viral load. PMID:7552477

  11. Comorbidity and high viral load linked to clinical presentation of respiratory human bocavirus infection.

    Science.gov (United States)

    Ghietto, Lucía María; Majul, Diego; Ferreyra Soaje, Patricia; Baumeister, Elsa; Avaro, Martín; Insfrán, Constanza; Mosca, Liliana; Cámara, Alicia; Moreno, Laura Beatriz; Adamo, Maria Pilar

    2015-01-01

    Human bocavirus (HBoV) is a new parvovirus associated with acute respiratory tract infection (ARTI). In order to evaluate HBoV significance as an agent of acute respiratory disease, we screened 1,135 respiratory samples from children and adults with and without symptoms during two complete calendar years. HBoV1 prevalence in patients with ARTI was 6.33 % in 2011 and 11.64 % in 2012, including neonatal and adult patients. HBoV1 was also detected in 3.77 % of asymptomatic individuals. The co-detection rate was 78.1 %. Among children, 87 % were clinically diagnosed with lower respiratory infection (no significant differences between patients with and without coinfection), and 31 % exhibited comorbidities. Pediatric patients with comorbidities were significantly older than patients without comorbidities. Patients with ARTI had either high or low viral load, while controls had only low viral load, but there were no clinical differences between patients with high or low viral load. In conclusion, we present evidence of the pathogenic potential of HBoV1 in young children with ARTI. Since patients with HBoV1-single infection are not significantly different from those with coinfection with respect to clinical features, the virus can be as pathogenic by itself as other respiratory agents are. Furthermore, an association between high HBoV1 load and disease could not be demonstrated in this study, but all asymptomatic individuals had low viral loads. Also, children with comorbidities are susceptible to HBoV1 infection at older ages than previously healthy children. Thus, the clinical presentation of infection may occur depending on both viral load and the particular interaction between the HBoV1 and the host. PMID:25269520

  12. Mechanism of antibody-mediated viral clearance in immunotherapy of respiratory syncytial virus infection of cotton rats.

    OpenAIRE

    Prince, G A; Hemming, V G; Horswood, R L; Baron, P A; Murphy, B R; Chanock, R M

    1990-01-01

    Antibody-mediated clearance of respiratory syncytial virus from cotton rat pulmonary tissues occurs in the absence of complement and in the absence of the Fc portion of the immunoglobulin G molecule, suggesting that complement-independent, cell-independent neutralization is the major mechanism of clearance.

  13. 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

    Directory of Open Access Journals (Sweden)

    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.

  14. Viral Load Drives Disease in Humans Experimentally Infected with Respiratory Syncytial Virus

    OpenAIRE

    DeVincenzo, John P.; Wilkinson, Tom; Vaishnaw, Akshay; Cehelsky, Jeff; Meyers, Rachel; Nochur, Saraswathy; Harrison, Lisa; Meeking, Patricia; Mann, Alex; Moane, Elizabeth; Oxford, John; Pareek, Rajat; Moore, Ryves; Walsh, Ed; Studholme, Robert

    2010-01-01

    Rationale: Respiratory syncytial virus (RSV) is the leading cause of childhood lower respiratory infection, yet viable therapies are lacking. Two major challenges have stalled antiviral development: ethical difficulties in performing pediatric proof-of-concept studies and the prevailing concept that the disease is immune-mediated rather than being driven by viral load.

  15. The Number of Herpes Simplex Virus-Infected Neurons and the Number of Viral Genome Copies per Neuron Correlate with the Latent Viral Load in Ganglia*

    OpenAIRE

    Hoshino, Yo; Qin, Jing; Follmann, Dean; Cohen, Jeffrey I.; Straus, Stephen E

    2007-01-01

    The latent viral load is the most important factor that predicts reactivation rates of animals latently infected with herpes simplex virus (HSV). To estimate the latent viral load, individual latently infected mouse trigeminal ganglia were dispersed into single cell suspensions and plated into 96-well real-time PCR plates, and HSV-2 genome copies were measured. By assuming a Poisson distribution for both the number of HSV-2 infected cells per well and the number of HSV-2 genome copies per inf...

  16. Detectable HIV Viral Load in Kenya: Data from a Population-Based Survey

    Science.gov (United States)

    Cherutich, Peter; Kim, Andrea A.; Kellogg, Timothy A.; Sherr, Kenneth; Waruru, Anthony; De Cock, Kevin M.; Rutherford, George W.

    2016-01-01

    Introduction At the individual level, there is clear evidence that Human Immunodeficiency Virus (HIV) transmission can be substantially reduced by lowering viral load. However there are few data describing population-level HIV viremia especially in high-burden settings with substantial under-diagnosis of HIV infection. The 2nd Kenya AIDS Indicator Survey (KAIS 2012) provided a unique opportunity to evaluate the impact of antiretroviral therapy (ART) coverage on viremia and to examine the risks for failure to suppress viral replication. We report population-level HIV viral load suppression using data from KAIS 2012. Methods Between October 2012 to February 2013, KAIS 2012 surveyed household members, administered questionnaires and drew serum samples to test for HIV and, for those found to be infected with HIV, plasma viral load (PVL) was measured. Our principal outcome was unsuppressed HIV viremia, defined as a PVL ≥ 550 copies/mL. The exposure variables included current treatment with ART, prior history of an HIV diagnosis, and engagement in HIV care. All point estimates were adjusted to account for the KAIS 2012 cluster sampling design and survey non-response. Results Overall, 61·2% (95% CI: 56·4–66·1) of HIV-infected Kenyans aged 15–64 years had not achieved virological suppression. The base10 median (interquartile range [IQR]) and mean (95% CI) VL was 4,633 copies/mL (0–51,596) and 81,750 copies/mL (59,366–104,134), respectively. Among 266 persons taking ART, 26.1% (95% CI: 20.0–32.1) had detectable viremia. Non-ART use, younger age, and lack of awareness of HIV status were independently associated with significantly higher odds of detectable viral load. In multivariate analysis for the sub-sample of patients on ART, detectable viremia was independently associated with younger age and sub-optimal adherence to ART. Discussion This report adds to the limited data of nationally-representative surveys to report population- level virological

  17. Detectable HIV Viral Load in Kenya: Data from a Population-Based Survey.

    Directory of Open Access Journals (Sweden)

    Peter Cherutich

    Full Text Available At the individual level, there is clear evidence that Human Immunodeficiency Virus (HIV transmission can be substantially reduced by lowering viral load. However there are few data describing population-level HIV viremia especially in high-burden settings with substantial under-diagnosis of HIV infection. The 2nd Kenya AIDS Indicator Survey (KAIS 2012 provided a unique opportunity to evaluate the impact of antiretroviral therapy (ART coverage on viremia and to examine the risks for failure to suppress viral replication. We report population-level HIV viral load suppression using data from KAIS 2012.Between October 2012 to February 2013, KAIS 2012 surveyed household members, administered questionnaires and drew serum samples to test for HIV and, for those found to be infected with HIV, plasma viral load (PVL was measured. Our principal outcome was unsuppressed HIV viremia, defined as a PVL ≥ 550 copies/mL. The exposure variables included current treatment with ART, prior history of an HIV diagnosis, and engagement in HIV care. All point estimates were adjusted to account for the KAIS 2012 cluster sampling design and survey non-response.Overall, 61·2% (95% CI: 56·4-66·1 of HIV-infected Kenyans aged 15-64 years had not achieved virological suppression. The base10 median (interquartile range [IQR] and mean (95% CI VL was 4,633 copies/mL (0-51,596 and 81,750 copies/mL (59,366-104,134, respectively. Among 266 persons taking ART, 26.1% (95% CI: 20.0-32.1 had detectable viremia. Non-ART use, younger age, and lack of awareness of HIV status were independently associated with significantly higher odds of detectable viral load. In multivariate analysis for the sub-sample of patients on ART, detectable viremia was independently associated with younger age and sub-optimal adherence to ART.This report adds to the limited data of nationally-representative surveys to report population- level virological suppression. We established heterogeneity across the

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

    Directory of Open Access Journals (Sweden)

    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.

  19. Cell-Mediated Immunity in Elite Controllers Naturally Controlling HIV Viral Load

    OpenAIRE

    Genovese, Luca; Nebuloni, Manuela; Alfano, Massimo

    2013-01-01

    The natural course of human immunodeficiency virus (HIV) infection is characterized by high viral load, depletion of immune cells, and immunodeficiency, ultimately leading to acquired immunodeficiency syndrome phase and the occurrence of opportunistic infections and diseases. Since the discovery of HIV in the early 1980s a naturally selected population of infected individuals has been emerged in the last years, characterized by being infected for many years, with viremia constantly below dete...

  20. Cerebrospinal fluid human immunodeficiency virus viral load in patients with neurosyphilis

    OpenAIRE

    Almeida, Sergio Monteiro de; Bhatt, Archana; Riggs, Patricia K.; Durelle, Janis; Lazzaretto, Deborah; Marquie-Beck, Jennifer; McCutchan, Allen; Letendre, Scott; Ellis, Ronald

    2010-01-01

    Syphilis is a frequent coinfection with human immunodeficiency virus (HIV). Whereas systemic syphilis infection increases plasma HIV RNA levels (viral load; VL), effects of syphilis on cerebrospinal fluid (CSF) VL are unknown. We hypothesized that intrathecal immune activation in neurosyphilis would selectively increase CSF VL in coinfected patients. In this study, HIV-infected research subjects (N = 225) were categorized into three groups based on serum rapid plasma reagin (RPR), microhemagl...

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

    OpenAIRE

    Laura Perez-Martinez; Isabel Sanjoaquin; Maria Rivero; Desiré Gil-Pérez; Santiago Letona; Carmen Irigoyen Olaiz; Piedad Arazo; Jose Ramón Blanco

    2014-01-01

    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 ...

  2. Increase in Viral Load, Viral Integration, and Gain of Telomerase Genes during Uterine Cervical Carcinogenesis can be Simultaneously Assessed by the HPV 16/18 MLPA-Assay

    OpenAIRE

    Theelen, Wendy; Speel, Ernst-Jan M; Herfs, Michael; Reijans, Martin; Simons, Guus; Meulemans, Els V.; Baldewijns, Marcella M.; Ramaekers, Frans C. S.; Somja, Joan; Delvenne, Philippe; Hopman, Anton H. N.

    2010-01-01

    Oncogenic human papillomavirus (HPV) infection is the most important risk factor in cervical carcinogenesis cases; high viral loads, viral integration into the host genome, and gain of the telomerase-related genes, TERT and TERC, are all factors associated with progression to cancer. A recently developed multiparameter HPV 16/18 multiplex ligation-dependent probe amplification (MLPA) assay, which allows the simultaneous assessment of these factors, was applied to a series of 67 normal and (pr...

  3. 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

  4. 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; Christensen, Peer Brehm; Laursen, Alex Lund; Bentzen-Petersen, Anne; Møller, Jørn Munkhof; Weis, Nina Margrethe

    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)....

  5. 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; Christensen, Peer Brehm; Laursen, Alex Lund; Bentzen-Petersen, Anne; Møller, Jørn M; Weis, Nina; Nielsen, Henrik Ib; Tage-Jensen, U.

    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)....

  6. PD-1 blockade in chronically HIV-1-infected humanized mice suppresses viral loads.

    Directory of Open Access Journals (Sweden)

    Edward Seung

    Full Text Available An estimated 34 million people are living with HIV worldwide (UNAIDS, 2012, with the number of infected persons rising every year. Increases in HIV prevalence have resulted not only from new infections, but also from increases in the survival of HIV-infected persons produced by effective anti-retroviral therapies. Augmentation of anti-viral immune responses may be able to further increase the survival of HIV-infected persons. One strategy to augment these responses is to reinvigorate exhausted anti-HIV immune cells present in chronically infected persons. The PD-1-PD-L1 pathway has been implicated in the exhaustion of virus-specific T cells during chronic HIV infection. Inhibition of PD-1 signaling using blocking anti-PD-1 antibodies has been shown to reduce simian immunodeficiency virus (SIV loads in monkeys. We now show that PD-1 blockade can improve control of HIV replication in vivo in an animal model. BLT (Bone marrow-Liver-Thymus humanized mice chronically infected with HIV-1 were treated with an anti-PD-1 antibody over a 10-day period. The PD-1 blockade resulted in a very significant 45-fold reduction in HIV viral loads in humanized mice with high CD8(+ T cell expression of PD-1, compared to controls at 4 weeks post-treatment. The anti-PD-1 antibody treatment also resulted in a significant increase in CD8(+ T cells. PD-1 blockade did not affect T cell expression of other inhibitory receptors co-expressed with PD-1, including CD244, CD160 and LAG-3, and did not appear to affect virus-specific humoral immune responses. These data demonstrate that inhibiting PD-1 signaling can reduce HIV viral loads in vivo in the humanized BLT mouse model, suggesting that blockade of the PD-1-PD-L1 pathway may have therapeutic potential in the treatment of patients already infected with the AIDS virus.

  7. The Association of HIV Viral Load with Indirect Markers of Liver Injury

    OpenAIRE

    Forrester, Janet E; Rhee, Martin S.; McGovern, Barbara H; Sterling, Richard K; Knox, Tamsin A; Terrin, Norma

    2011-01-01

    This study assessed the association of HIV RNA with indirect markers of liver injury including FIB-4 index, liver enzymes and platelet counts in a high-risk Hispanic population. The data were derived from a prospective study that included 138 HIV/hepatitis C (HCV) co-infected and 68 HIV-infected participants without hepatitis C or B co-infection (mono-infected). In unadjusted analyses, detectable HIV viral load (vs. undetectable, 1.45 in the HIV/HCV co-infected group and 70% greater odds of ...

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

    OpenAIRE

    V. B. Musatov; Yakovlev, A. A.; S. G. Andreeva; M. V. Ivanova

    2015-01-01

    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 opportunist...

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

    Directory of Open Access Journals (Sweden)

    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.

  10. Circulating virus load determines the size of bottlenecks in viral populations progressing within a host.

    Directory of Open Access Journals (Sweden)

    Serafín Gutiérrez

    Full Text Available For any organism, population size, and fluctuations thereof, are of primary importance in determining the forces driving its evolution. This is particularly true for viruses--rapidly evolving entities that form populations with transient and explosive expansions alternating with phases of migration, resulting in strong population bottlenecks and associated founder effects that increase genetic drift. A typical illustration of this pattern is the progression of viral disease within a eukaryotic host, where such demographic fluctuations are a key factor in the emergence of new variants with altered virulence. Viruses initiate replication in one or only a few infection foci, then move through the vasculature to seed secondary infection sites and so invade distant organs and tissues. Founder effects during this within-host colonization might depend on the concentration of infectious units accumulating and circulating in the vasculature, as this represents the infection dose reaching new organs or "territories". Surprisingly, whether or not the easily measurable circulating (plasma virus load directly drives the size of population bottlenecks during host colonization has not been documented in animal viruses, while in plants the virus load within the sap has never been estimated. Here, we address this important question by monitoring both the virus concentration flowing in host plant sap, and the number of viral genomes founding the population in each successive new leaf. Our results clearly indicate that the concentration of circulating viruses directly determines the size of bottlenecks, which hence controls founder effects and effective population size during disease progression within a host.

  11. Spontaneous hepatitis C viral clearance and hepatitis C chronic infection are associated with distinct cytokine profiles in Mexican patients

    Directory of Open Access Journals (Sweden)

    Nora A Fierro

    2015-04-01

    Full Text Available The mechanisms related to the spontaneous clearance of hepatitis C virus (HCV have been primarily studied in regions where the infection is endemic. Results of prior studies have been extrapolated to populations with low endemicity, such as Mexico. Herein, we determined the cytokine profiles in serum samples from Mexican patients who spontaneously cleared HCV and patients chronically infected with HCV genotype 1a. Chronic HCV-infected patients displayed increased interleukin (IL-8 and regulated upon activation, normal T-cell expressed and secreted (CCL-5 secretion, whereas patients who spontaneously cleared HCV showed augmented levels of IL-1 alpha, tumour necrosis factor-alpha, transforming growth factor-beta, monocyte chemoattractant protein-2 (CCL-8, IL-13 and IL-15. Our study suggeststhat cytokine profiles may predict disease outcome during HCV infection.

  12. 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....

  13. The semen microbiome and its relationship with local immunology and viral load in HIV infection.

    Directory of Open Access Journals (Sweden)

    Cindy M Liu

    2014-07-01

    Full Text Available Semen is a major vector for HIV transmission, but the semen HIV RNA viral load (VL only correlates moderately with the blood VL. Viral shedding can be enhanced by genital infections and associated inflammation, but it can also occur in the absence of classical pathogens. Thus, we hypothesized that a dysregulated semen microbiome correlates with local HIV shedding. We analyzed semen samples from 49 men who have sex with men (MSM, including 22 HIV-uninfected and 27 HIV-infected men, at baseline and after starting antiretroviral therapy (ART using 16S rRNA gene-based pyrosequencing and quantitative PCR. We studied the relationship of semen bacteria with HIV infection, semen cytokine levels, and semen VL by linear regression, non-metric multidimensional scaling, and goodness-of-fit test. Streptococcus, Corynebacterium, and Staphylococcus were common semen bacteria, irrespective of HIV status. While Ureaplasma was the more abundant Mollicutes in HIV-uninfected men, Mycoplasma dominated after HIV infection. HIV infection was associated with decreased semen microbiome diversity and richness, which were restored after six months of ART. In HIV-infected men, semen bacterial load correlated with seven pro-inflammatory semen cytokines, including IL-6 (p = 0.024, TNF-α (p = 0.009, and IL-1b (p = 0.002. IL-1b in particular was associated with semen VL (r(2  = 0.18, p = 0.02. Semen bacterial load was also directly linked to the semen HIV VL (r(2 = 0.15, p = 0.02. HIV infection reshapes the relationship between semen bacteria and pro-inflammatory cytokines, and both are linked to semen VL, which supports a role of the semen microbiome in HIV sexual transmission.

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

    Directory of Open Access Journals (Sweden)

    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.

  15. Maraviroc and Other HIV-1 Entry Inhibitors Exhibit a Class-Specific Redistribution Effect That Results in Increased Extracellular Viral Load

    OpenAIRE

    Kramer, Victor G; Schader, Susan M.; Oliveira, Maureen; Colby-Germinario, Susan P.; Donahue, Daniel A.; Singhroy, Diane N; Tressler, Randy; Sloan, Richard D.; Mark A Wainberg

    2012-01-01

    HIV entry inhibitors, such as maraviroc (MVC), prevent cell-free viruses from entering the cells. In clinical trials, patients who were treated with MVC often displayed viral loads that were above the limit of conventional viral load detection compared to efavirenz-based regimens. We hypothesize that viruses blocked by entry inhibitors may be redistributed to plasma, where they artificially increase viral load measurements compared to those with the use of antiretroviral drugs (ARVs) that act...

  16. Factors associated with poor CD4 and viral load outcomes in patients with HIV/AIDS.

    Science.gov (United States)

    Syed, Imran Ahmed; Sulaiman, Syed Azhar Syed; Hassali, Mohammad Azmi; Syed, Shahzad Hasan; Shan, Lau Hui; Lee, Christopher K C

    2016-05-01

    Suboptimal viral suppression and CD4 response to antiretroviral treatment (HAART) is known to cause poor outcomes with the increase cost of treatment. We aimed to assess factors associated with such control among HIV/AIDS patients in Malaysia. Four hundred and six HIV/AIDS patients, using Antiretroviral Therapy (ART) for at least the past three months, treated as outpatients at medication therapy adherence clinics (MTAC) were recruited. CD4 cell counts, viral load readings along with co-variants such as socio-demographic factors, adverse drug reactions, comorbidities, and medication record were obtained. Statistical Package for Social Sciences (SPSS(®) ) version 18 and STATA IC(®) version 12 were used for data analysis. CD4 counts were found highest among those within the age category 41-50 years (390.43 ± 272.28), female (402.64 ± 276.14), other ethnicities (400.20 ± 278.04), and participants with no formal education (414.87 ± 290.90). Patients experiencing adverse effects had a 2.28 (95%CI:1.25-4.18) fold greater risk of poor CD4 control, while patients with comorbidities had 2.46 (95%CI:1.02-5.91) fold greater risk of mild viral suppression. Adverse drug reactions, co-morbidities were found to be significantly associated with poor immunological and virological outcomes in HIV/AIDS patients. However, a comprehensive evaluation is needed to better understand other confounders J. Med. Virol. 88:790-797, 2016. © 2015 Wiley Periodicals, Inc. PMID:26399724

  17. Number of Drinks to "Feel a Buzz" by HIV Status and Viral Load in Men.

    Science.gov (United States)

    McGinnis, Kathleen A; Fiellin, David A; Tate, Janet P; Cook, Robert L; Braithwaite, R Scott; Bryant, Kendall J; Edelman, E Jennifer; Gordon, Adam J; Kraemer, Kevin L; Maisto, Stephen A; Justice, Amy C

    2016-03-01

    The impact of HIV and its treatment on the effects of alcohol remain unclear. Blood alcohol concentrations have been noted to be higher in HIV infected individuals prior to antiretroviral initiation. Our goal was to compare number of drinks to "feel a buzz or high" among HIV infected and uninfected men, stratified by viral load (VL) suppression. Data includes 1478 HIV infected and 1170 uninfected men in the veterans aging cohort study who endorsed current drinking. Mean (SD) number of drinks to feel a buzz was 3.1 (1.7) overall. In multivariable analyses, HIV infected men reported a lower mean number of drinks to feel a buzz compared to uninfected men (coef = -14 for VL buzz. Future research on the relationship between alcohol and HIV should consider the role of VL suppression. PMID:26936030

  18. Cell-Mediated Immunity in Elite Controllers Naturally Controlling HIV Viral Load.

    Science.gov (United States)

    Genovese, Luca; Nebuloni, Manuela; Alfano, Massimo

    2013-01-01

    The natural course of human immunodeficiency virus (HIV) infection is characterized by high viral load, depletion of immune cells, and immunodeficiency, ultimately leading to acquired immunodeficiency syndrome phase and the occurrence of opportunistic infections and diseases. Since the discovery of HIV in the early 1980s a naturally selected population of infected individuals has been emerged in the last years, characterized by being infected for many years, with viremia constantly below detectable level and poor depletion of immune cells. These individuals are classified as "elite controllers (EC) or suppressors" and do not develop disease in the absence of anti-retroviral therapy. Unveiling host factors and immune responses responsible for the elite status will likely provide clues for the design of therapeutic vaccines and functional cures. Scope of this review was to examine and discuss differences of the cell-mediated immune responses between HIV+ individuals with disease progression and EC. PMID:23577012

  19. Cell-mediated Immunity in Elite Controllers Naturally Controlling HIV Viral Load

    Directory of Open Access Journals (Sweden)

    Luca eGenovese

    2013-04-01

    Full Text Available The natural course of HIV infection is characterized by high viral load, depletion of immune cells and immunodeficiency, ultimately leading to acquired immunodeficiency syndrome (AIDS phase and the occurrence of opportunistic infections and diseases.Since the discovery of HIV in the early 80’s a naturally selected population of infected individuals has been emerged in the last years, characterized by being infected for many years, with viremia constantly below detectable level and poor depletion of immune cells. These individuals are classified as elite controllers or suppressors and do not develop disease in the absence of anti-retroviral therapy.Unveiling host factors and immune responses responsible for the elite status will likely provide clues for the design of therapeutic vaccines and functional cures. Scope of this review was to examine and discuss differences of the cell-mediated immune responses between HIV+ individuals with disease progression and elite controllers.

  20. Sensitive and specific nested PCR assay for detection of rotavirus A in samples with a low viral load.

    Science.gov (United States)

    Mijatovic-Rustempasic, Slavica; Esona, Mathew D; Williams, Alice L; Bowen, Michael D

    2016-10-01

    Techniques such as the real-time reverse transcription-polymerase chain reaction (qRT-PCR) can detect RNA in samples with a low viral load. However, these amplicons typically are either too short or at insufficient concentrations for use in subsequent sequencing reactions for genotyping and detection confirmation. The assay developed in this study detects rotavirus G genotypes and P genotypes with viral loads as low as 6.2 and 8.2 copies per reaction, respectively. The assay was validated using a panel of 91 stool samples, 32 reference rotavirus strains, and 6 non-target enteric virus samples. PMID:27421626

  1. Proteomics approach to understand reduced clearance of mycobacteria and high viral titers during HIV-mycobacteria co-infection.

    Science.gov (United States)

    Ganji, Rakesh; Dhali, Snigdha; Rizvi, Arshad; Sankati, Swetha; Vemula, Mani Harika; Mahajan, Gaurang; Rapole, Srikanth; Banerjee, Sharmistha

    2016-03-01

    Environmental mycobacteria, highly prevalent in natural and artificial (including chlorinated municipal water) niches, are emerging as new threat to human health, especially to HIV-infected population. These seemingly harmless non-pathogenic mycobacteria, which are otherwise cleared, establish as opportunistic infections adding to HIV-associated complications. Although immune-evading strategies of pathogenic mycobacteria are known, the mechanisms underlying the early events by which opportunistic mycobacteria establish infection in macrophages and influencing HIV infection are unclear. Proteomics of phagosome-enriched fractions from Mycobacterium bovis Bacillus Calmette-Guérin (BCG) mono-infected and HIV-M. bovis BCG co-infected THP-1 cells by LC-MALDI-MS/MS revealed differential distribution of 260 proteins. Validation of the proteomics data showed that HIV co-infection helped the survival of non-pathogenic mycobacteria by obstructing phagosome maturation, promoting lipid biogenesis and increasing intracellular ATP equivalents. In turn, mycobacterial co-infection up-regulated purinergic receptors in macrophages that are known to support HIV entry, explaining increased viral titers during co-infection. The mutualism was reconfirmed using clinically relevant opportunistic mycobacteria, Mycobacterium avium, Mycobacterium kansasii and Mycobacterium phlei that exhibited increased survival during co-infection, together with increase in HIV titers. Additionally, the catalogued proteins in the study provide new leads that will significantly add to the understanding of the biology of opportunistic mycobacteria and HIV coalition. PMID:26332641

  2. Effects of external pressure loading on human skin blood flow measured by 133Xe clearance

    International Nuclear Information System (INIS)

    Forearm skin blood flow was measured during external pressure loading in normal human subjects using 133Xe washout from intracutaneous injection sites. Pressures ranging between 5 and 150 mmHg were applied through a 3-cm-diameter disc placed over the site of flow determination. The pressure was maintained constant by a servo-controlled loading mechanism. Flow decreased with pressures from 5 to 10 and 30 to 150 mmHg, but remained constant with pressures from 10 to 30 mmHg. Reactive hyperemia occurred following removal of pressures of 90 mmHg or greater, but did not occur following removal of lower pressures. The pressure-flow curve for parasacral skin of paraplegic subjects closely paralleled the pressure-flow curve of normal skin at pressures tested: 5 to 15 mmHg. These data are interpreted to demonstrate autoregulation of skin blood flow. Autoregulation in parasacral skin of paraplegic subjects suggests a peripheral mechanism. The occurrence of hyperemia at pressures which exceed the ability of skin to autoregulate suggests that both autoregulation and post occlusion hyperemia may have the same mechanism

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

    Directory of Open Access Journals (Sweden)

    V. B. Musatov

    2015-11-01

    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

  4. End-of-Treatment-Response in Patients Treated for Hepatitis C Virus with Standard Interferon and Ribavirin Based on Viral Load

    International Nuclear Information System (INIS)

    Objective: To determine the End-of-Treatment-Response (ETR) to standard interferon and ribavirin based regimen in patients of chronic hepatitis C and to compare the ETR response in low and high viral load groups. Study Design: Descriptive study. Place and Duration of Study: Virology Department, Armed Forces Institute of Pathology (AFIP), Rawalpindi, from March 2012 to May 2013. Methodology: Patients with chronic hepatitis C virus infection were included in the study. Pre-treatment viral load was determined by RoboGene Quantification kit. Based on viral load, the 400 patients were divided into two equal groups of low viral load (< 800,000 IU/ml) and high viral load (> 800,000 IU/ml). The patients were treated with standard interferon alpha (3 million units subcutaneously thrice weekly) and ribavirin (10.6 mg/kg body weight) for 6 months. ETR was measured using Sacace Biotechnologies Qualitative kit. Chi-square test was used to compare the ETR in the two viral load groups. P-value < 0.05 was considered as significant. Results: Out of 400 patients, 206 (51.5%) were males and 194 (48.5%) were females. Two hundred seventy (67.5%) patients achieved ETR and 130 (35.5%) failed to do so. In low viral load group, 145 (72.5%) patients achieved and 55 (27.5%) patients did not achieve ETR. In high viral load group, 123 (61.5%) patients achieved and 77 (38.5%) did not achieve ETR. The difference in ETR between low and high viral load groups was statistically significant (p=0.019). Conclusion: End-of-treatment-response in patients treated for hepatitis C virus with standard interferon and ribavirin was greater in patients with low viral load as compared to patients with high viral load. (author)

  5. 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. PMID:25193072

  6. 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

    , the predicted proportion of potential life-years survived was 83% with viral load monitoring (switch when viral load >500 copies per mL), 82% with CD4 cell count monitoring (switch at 50% drop from peak), and 82% with clinical monitoring (switch when two new WHO stage 3 events or a WHO stage 4 event occur...

  7. Abbott RealTime HIV-1 m2000rt viral load testing: Manual extraction versus the automated m2000sp extraction

    OpenAIRE

    Scott, Lesley E.; Crump, John A.; Msuya, Emma; Morrissey, Anne B.; Venter, Willem F.; Stevens, Wendy S.

    2010-01-01

    The Abbott RealTime HIV-1 assay is a real-time nucleic acid amplification assay available for HIV-1 viral load quantitation. The assay has a platform for automated extraction of viral RNA from plasma or dried blood spot samples, and an amplification platform with real time fluorescent detection. Overall, this study found no clinically relevant differences in viral load, if samples were extracted manually.

  8. Clinical Factors and Viral Load Influencing Severity of Acute Hepatitis A.

    Directory of Open Access Journals (Sweden)

    Hyun Woong Lee

    Full Text Available Clinical manifestations of hepatitis A virus (HAV infection vary from mild to fulminant hepatic failure (FHF in adults. We investigated the relationship between laboratory findings, including viral load, and clinical outcomes in patients with acute hepatitis A (AHA and evaluated predictive factors for severe acute hepatitis (s-AH.We analyzed the clinical manifestations of AHA in 770 patients. Patients with a prothrombin time (PT of less than 40% of normal were classified as s-AH and included 4 patients with FHF, 11 patients with acute renal failure, and 3 patients with prolonged jaundice (n = 128. Other patients were defined as mild acute hepatitis (m-AH (n = 642. Serum samples were obtained from 48 patients with acute hepatitis A. Among them, 20 with s-AH, and 28 with m-AH, were tested for HAV RNA titer.In a multivariate analysis, age (HR = 1.042, P = 0.041, peak creatinine (HR = 4.014, P = 0.001, bilirubin (HR = 1.153, P = 0.003, alanine aminotransferase (ALT (HR = 1.001, P < 0.001, initial lactate dehydrogenase (LDH (HR = 1.000, P = 0.045 and total cholesterol (HR = 0.978, P < 0.001 were independent factors for s-AH. Serum HAV RNA was detected in 20/20 (100% patients with s-AH and 22/28 (78.6% patients with m-AH. In a multivariate analysis of the 48 patients who were tested for HAV RNA, peak ALT (HR = 1.001, P = 0.004 and HAV RNA titer (HR = 2.076, P = 0.012 were independent factors for s-AH.Clinical factors including age, peak creatinine, bilirubin, ALT, initial LDH and total cholesterol were independent factors for s-AH in a multivariate analysis. In particular, HAV load strongly correlated with the severity of hepatitis A.

  9. 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......-count, CD4+HLA-DR+, CD8+HLA-DR+CD38+, CD4+CD45RA-CD45RO+, CD8+CD45RA-CD45RO+, CD4+CD45RA+CD62L+, CD8+CD45RA+CD62L+ T cells, IgG or IgM. In conclusion, RV was associated with increased blood levels of soluble immune activation markers in HAART-treated HIV-1-infected patients. The finding that RV was...... 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...

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

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    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

  11. Human Papillomavirus 16, 18, 31 and 45 viral load, integration and methylation status stratified by cervical disease stage

    International Nuclear Information System (INIS)

    Persistent infection with oncogenic Human Papillomavirus (HPV) is associated with the development of cervical cancer with each genotype differing in their relative contribution to the prevalence of cervical disease. HPV DNA testing offers improved sensitivity over cytology testing alone but is accompanied by a generally low specificity. Potential molecular markers of cervical disease include type-specific viral load (VL), integration of HPV DNA into the host genome and methylation of the HPV genome. The aim of this study was to evaluate the relationship between HPV type-specific viral load, integration and methylation status and cervical disease stage in samples harboring HPV16, HPV18, HPV31 or HPV45. Samples singly infected with HPV16 (n = 226), HPV18 (n = 32), HPV31 (n = 75) or HPV45 (n = 29) were selected from a cohort of 4,719 women attending cervical screening in England. Viral load and integration status were determined by real-time PCR while 3’L1-URR methylation status was determined by pyrosequencing or sequencing of multiple clones derived from each sample. Viral load could differentiate between normal and abnormal cytology with a sensitivity of 75% and a specificity of 80% (odds ratio [OR] 12.4, 95% CI 6.2–26.1; p < 0.001) with some variation between genotypes. Viral integration was poorly associated with cervical disease. Few samples had fully integrated genomes and these could be found throughout the course of disease. Overall, integration status could distinguish between normal and abnormal cytology with a sensitivity of 72% and a specificity of 50% (OR 2.6, 95% CI 1.0–6.8; p = 0.054). Methylation levels were able to differentiate normal and low grade cytology from high grade cytology with a sensitivity of 64% and a specificity of 82% (OR 8.2, 95% CI 3.8–18.0; p < 0.001). However, methylation varied widely between genotypes with HPV18 and HPV45 exhibiting a broader degree and higher magnitude of methylated CpG sites than HPV16 and HPV31. This

  12. Epstein-Barr virus: general factors, virus-related diseases and measurement of viral load after transplant

    Directory of Open Access Journals (Sweden)

    Luciana Cristina Fagundes Gequelin

    2011-10-01

    Full Text Available The Epstein-Barr virus is responsible for infectious mononucleosis syndrome and is also closely associated to several types of cancer. The main complication involving Epstein-Barr virus infection, both in recipients of hematopoietic stem cells and solid organs, is post-transplant lymphoproliferative disease. The importance of this disease has increased interest in the development of laboratory tools to improve post-transplant monitoring and to detect the disease before clinical evolution. Viral load analysis for Epstein-Barr virus through real-time polymerase chain reaction is, at present, the best tool to measure viral load. However, there is not a consensus on which sample type is the best for the test and what is its predictive value for therapeutic interventions.

  13. KINETICS OF VIRAL LOADS AND GENOTYPIC ANALYSIS OF ELEPHANT ENDOTHELIOTROPIC HERPESVIRUS-1 INFECTION IN CAPTIVE ASIAN ELEPHANTS (ELEPHAS MAXIMUS)

    OpenAIRE

    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

    2013-01-01

    Elephant endotheliotropic herpesviruses (EEHVs) can cause fatal hemorrhagic disease in juvenile Asian elephants (Elephas 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 reac...

  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.

    2013-01-01

    Elephant endotheliotropic herpesviruses (EEHVs) can cause fatal hemorrhagic disease in juvenile Asian elephants (Elephas 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. PMID:23505702

  15. Age and Ebola viral load correlate with mortality and survival time in 288 Ebola virus disease patients

    OpenAIRE

    Jin Li; Hui-Juan Duan; Hao-Yang Chen; Ying-Jie Ji; Xin Zhang; Yi-Hui Rong; Zhe Xu; Li-Jian Sun; Ji-Yuan Zhang; Li-Ming Liu; Bo Jin; Jian Zhang; Ning Du; Hai-Bin Su; Guang-Ju Teng

    2016-01-01

    Background: A Chinese medical team managed Ebola virus disease (EVD) patients in Sierra Leone from October 2014 to March 2015 and attended to 693 suspected patients, of whom 288 had confirmed disease. Methods: A retrospective study was conducted of the 288 patients with confirmed disease. Clinical symptoms, manifestations, and serum viral load were analyzed and compared among the different groups for mortality and survival time. Results: Among the 288 confirmed EVD patients (149 male an...

  16. Ring finger protein 39 genetic variants associate with HIV-1 plasma viral loads and its replication in cell culture

    OpenAIRE

    Lin, Ying-Ju; Chen, Chia-Yen; Jeang, Kuan-Teh; Liu, Xiang; Wang, Jen-Hsien; Hung, Chien-Hui; Tsang, Hsinyi; Lin, Ting-Hsu; Liao, Chiu-Chu; Huang, Shao-Mei; Lin, Cheng-Wen; Ho, Mao-Wang; Chien, Wen-Kuei; Chen, Jin-Hua; Ho, Tsung-Jung

    2014-01-01

    Background The human immunodeficiency virus (HIV-1) exploits host proteins to complete its life cycle. Genome-wide siRNA approaches suggested that host proteins affect HIV-1 replication. However, the results barely overlapped. RING finger protein 39 (RNF39) has been identified from genome-wide association studies. However, its function during HIV-1 replication remains unclear. Methods and results We investigated the relationship between common RNF39 genetic variants and HIV-1 viral loads. The...

  17. Is HCV core antigen a reliable marker of viral load? An evaluation of HCV core antigen automated immunoassay

    OpenAIRE

    Hadziyannis, Emilia; Minopetrou, Martha; Georgiou, Anastasia; Spanou, Fotini; Koskinas, John

    2013-01-01

    Background Hepatitis C viral (HCV) load detection and quantification is routinely accomplished by HCV RNA measurement, an expensive but essential test, both for the diagnosis and treatment of chronic hepatitis C (CHC). HCV core antigen (Ag) testing has been suggested as an attractive alternative to molecular diagnostics. The aim of the study was to evaluate an automated chemiluminescent immunoassay (CLIA) for HCV core Ag measurement in comparison to quantitative HCV RNA determination. Methods...

  18. Impact of Adherence Counseling Dose on Antiretroviral Adherence and HIV Viral Load among HIV-Infected Methadone Maintained Drug Users

    OpenAIRE

    Cooperman, Nina A.; Heo, Moonseong; Berg, Karina M.; Li, Xuan; Litwin, Alain H.; Nahvi, Shadi; Arnsten, Julia H.

    2012-01-01

    Adherence counseling can improve antiretroviral adherence and related health outcomes in HIV-infected individuals. However, little is known about how much counseling is necessary to achieve clinically significant effects. We investigated antiretroviral adherence and HIV viral load relative to the number of hours of adherence counseling received by 60 HIV-infected drug users participating in a trial of directly observed antiretroviral therapy delivered in methadone clinics. Our adherence couns...

  19. Cytomegalovirus Viral Load and Virus-specific Immune Reconstitution after Peripheral Blood Stem Cell versus Bone Marrow Transplantation

    OpenAIRE

    Guerrero, A; Riddell, S. R.; Storek, J.; Stevens-Ayers, T; Storer, B; Zaia, J A; Forman, S; Negrin, R S; Chauncey, T.; Bensinger, W.; Boeckh, M.

    2011-01-01

    Peripheral blood stem cell (PBSC) products contain more T cells and monocytes when compared to bone marrow (BM), leading to fewer bacterial and fungal infections. CMV viral load and disease as well as CMV-specific immune reconstitution were compared in patients enrolled in a randomized trial comparing PSBC and BM transplantation. There was a higher rate of CMV infection and disease during the first 100 days after transplantation among PBSC recipients (any antigenemia/DNAemia: PBSC, 63% vs. BM...

  20. Human papillomavirus type 16 viral load is decreased following a therapeutic vaccination.

    Science.gov (United States)

    Coleman, Hannah N; Greenfield, William W; Stratton, Shawna L; Vaughn, Rita; Kieber, Alexander; Moerman-Herzog, Andrea M; Spencer, Horace J; Hitt, Wilbur C; Quick, Charles Matthew; Hutchins, Laura F; Mackintosh, Samuel G; Edmondson, Ricky D; Erickson, Stephen W; Nakagawa, Mayumi

    2016-05-01

    In the dose-escalation phase of a Phase I clinical trial in which six subjects each were vaccinated with PepCan at the 50, 100, 250, and 500 μg per peptide dose, the 50 μg dose showed the best histological regression rate. Ten additional subjects were vaccinated at this dose in the final dose phase. As with the dose-escalation phase, no dose-limiting toxicities were observed. Overall, the histological regression rates were 50 % at the 50 μg dose (7 of 14) and 100 μg dose (3 of 6), and 45 % overall (14 of 31). Of subjects in whom HPV type 16 (HPV 16) was detected at entry, it became undetectable in three subjects after vaccination, and the viral loads significantly decreased in nine subjects in whom HPV 16 infection was detected at entry and exit (p = 0.008). Immune profiling revealed increased T-helper type 1 cells after vaccinations (p = 0.02 and 0.0004 after 2 and 4 vaccinations, respectively). T-helper type 2 cells initially increased after two vaccinations (p = 0.01), but decreased below the baseline level after four vaccinations although not significantly. Pre-vaccination regulatory T cell levels were significantly lower in histological responders compared to non-responders (p = 0.03). Feasibility of testing plasma for multiplex cytokine/chemokine analysis and of performing proteomic analysis of PBMCs was examined for potentially identifying biomarkers in the future. While these analyses are feasible to perform, attention needs to be given to how soon the blood samples would be processed after phlebotomy. As sufficient safety of PepCan has been demonstrated, enrollment for the Phase II clinical trial has been opened. PMID:26980480

  1. Viral load, integration and methylation of E2BS3 and 4 in human papilloma virus (HPV 16-positive vaginal and vulvar carcinomas.

    Directory of Open Access Journals (Sweden)

    Gabriella Lillsunde Larsson

    Full Text Available To investigate if viral load, integration and methylation of E2BS3 and 4 represent different ways of tumor transformation in vaginal and vulvar carcinoma and to elucidate its clinical impact.Fifty-seven samples, positive for HPV16, were selected for the study. Detection of viral load was made with realtime-PCR using copy numbers of E6 and integration was calculated from comparing E2 to E6-copies. Methylation of E2BS3 and 4 was analysed using bisulphite treatment of tumor DNA, followed by PCR and pyrosequencing.Vaginal tumors were found to have a higher viral load (p = 0.024 compared to vulvar tumors but a high copy number (> median value, 15,000 as well as high methylation (>50% was significantly (p = 0.010 and p = 0.045 associated with a worse cancer-specific survival rate in vulvar carcinoma, but not in vaginal carcinoma. Four groups could be defined for the complete series using a Cluster Two step analysis; (1 tumors holding episomal viral DNA, viral load below 150,000 copies not highly methylated (n = 25, 46.3%; (2 tumors harboring episomal viral DNA and being highly methylated (>50%; n = 6, 11.1%; (3 tumors with viral DNA fully integrated (n = 11, 20.4%, and (4 tumors harboring episomal viral DNA and being medium- or unmethylated ( total mean value 150,000; n = 12, 22.2%. The completely integrated tumors were found to be distinct group, whilst some overlap between the groups with high methylation and high viral load was observed.HPV16- related integration, methylation in E2BS3 and 4 and viral load may represent different viral characteristics driving vaginal and vulvar carcinogenesis. HPV16- related parameters were found to be of clinical importance in the vulvar series only.

  2. 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

  3. 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.

  4. 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.

  5. Prevalence and Viral Load of Human Parvovirus B19 (B19V) Among Blood Donors in South-East Brazil.

    Science.gov (United States)

    Slavov, Svetoslav Nanev; Otaguiri, Katia Kaori; Covas, Dimas Tadeu; Kashima, Simone

    2016-06-01

    The infection of human parvovirus B19 (B19V) is a common event in the general population, including volunteer blood donors. In some cases it can be asymptomatic and can remain persistent for a long period of time. The objective of this study was to examine the B19V DNA prevalence and viral load in first-time volunteer blood donors. Blood samples were collected from 91 primary blood donors at the Regional Blood Center of Ribeirão Preto, Southeast Brazil. Viral detection and quantitation was performed by an in-house TaqMan(®) real-time PCR with high sensitivity. B19V DNA was detected in one male blood donor (1.0 %) and was characterized by a very low viral load (537.36 copies/mL). Our studies demonstrate that B19V DNA at low titer may be present in apparently healthy individuals. Sensitive molecular diagnostic tools can be applied for the screening of fresh blood derived products in order to prevent transfusion-transmitted B19V infection. PMID:27408426

  6. Molecular investigations on the prevalence and viral load of enteric viruses in pigs from five European countries.

    Science.gov (United States)

    Zhou, Weiguang; Ullman, Karin; Chowdry, Vinay; Reining, Márta; Benyeda, Zsófia; Baule, Claudia; Juremalm, Mikael; Wallgren, Per; Schwarz, Lukas; Zhou, Enmin; Pedrero, Sonia Pina; Hennig-Pauka, Isabel; Segales, Joaquim; Liu, Lihong

    2016-01-15

    Enteric viral infections in pigs may cause diarrhea resulting in ill-thrift and substantial economic losses. This study reports the enteric infections with porcine astrovirus type 4 (PAstV4), porcine group A rotavirus (GARV), porcine group C rotavirus (GCRV), porcine circovirus type 2 (PCV2) and porcine kobuvirus (PKoV) in 419 pigs, comprising both healthy and diarrheic animals, from 49 farms in five European countries (Austria, Germany, Hungary, Spain and Sweden). Real-time RT-PCR assays were developed to test fecal samples and to compare the prevalence and viral load in relation to health status, farms of origin and age groups. The results showed that PAstV4 (70.4%) was the dominant virus species, followed by PKoV (56.7%), PCV2 (42.2%), GCRV (3%) and GARV (0.9%). Diarrheic pigs had a higher viral load of PAstV4 in the nursery and growing-finishing groups. Rotaviruses were mainly detected in diarrheic pigs, whereas PCV2 was more often detected in clinically healthy than in diarrheic pigs, suggesting that most PCV2 infections were subclinical. PAstV4, PCV2 and PKoV were considered ubiquitous in the European pig livestock and co-infections among them were frequent, independently of the disease status, in contrast to a low prevalence of classical rotavirus infections. PMID:26711031

  7. Fatal and nonfatal AIDS and non-AIDS events in HIV-1-positive individuals with high CD4 cell counts according to viral load strata

    DEFF Research Database (Denmark)

    Reekie, Joanne; Gatell, Jose M; Yust, Israel;

    2011-01-01

    This study compared the incidence of fatal and nonfatal AIDS and non-AIDS events in HIV-positive individuals with a CD4 cell count more than 350¿ cells/µl among viral load strata: low (......This study compared the incidence of fatal and nonfatal AIDS and non-AIDS events in HIV-positive individuals with a CD4 cell count more than 350¿ cells/µl among viral load strata: low (...

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

    OpenAIRE

    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 collaboration study. Methods: A total of 158 385 pairs of consecutive viral load and CD4+ cell count simultaneously measured from 34 384 ART-naive individuals in the COHERE database were analysed. Annual...

  9. Switching to second-line antiretroviral therapy in resource-limited settings: comparison of programmes with and without viral load monitoring.

    OpenAIRE

    Keiser, Olivia; Tweya, Hannock; Boulle, Andrew; Braitstein, Paula; Schecter, Mauro; Brinkhof, Martin W. G; DABIS, François; Tuboi, Suely; Sprinz, Eduardo; Pujades-Rodriguez, Mar; Calmy, Alexandra; Kumarasamy, Nagalingeswaran; Nash, Denis; Jahn, Andreas; Macphail, Patrick

    2009-01-01

    BACKGROUND: In high-income countries, viral load is routinely measured to detect failure of antiretroviral therapy (ART) and guide switching to second-line ART. Viral load monitoring is not generally available in resource-limited settings. We examined switching from nonnucleoside reverse transcriptase inhibitor (NNRTI)-based first-line regimens to protease inhibitor-based regimens in Africa, South America and Asia. DESIGN AND METHODS: Multicohort study of 17 ART programmes. All sites monitore...

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

    OpenAIRE

    F. Nakagawa; Grp, NHPW; Ep, COHIV; EuroCoord

    2014-01-01

    Objectives: Among antiretroviral therapy (ART)-naive individuals, viral load levels tend to increase and CD4þ 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 collaboration study. Methods: A total of 158 385 pairs of consecutive viral load and CD4þ cell count simultaneously measured from 34 384 ART-naive individuals in the COHERE database ...

  11. 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....

  12. 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.

  13. Epitope specificity is critical for high and moderate avidity cytotoxic T lymphocytes associated with control of viral load and clinical disease in horses with equine infectious anemia virus

    International Nuclear Information System (INIS)

    Equine infectious anemia virus (EIAV) is a lentivirus that causes persistent infections in horses. We hypothesized that high-avidity CTL specific for nonvariable epitopes might be associated with low viral load and minimal disease in EIAV-infected horses. To test this hypothesis, memory CTL (CTLm) responses were analyzed in two infected horses with high plasma viral loads and recurrent disease (progressors), and in two infected horses with low-to-undetectable viral loads and mild disease (nonprogressors). High-avidity CTLm in one progressor recognized an envelope gp90 epitope, and the data documented for the first time in EIAV that viral variation led to CTL escape. Each of the nonprogressors had high-to-moderate avidity CTLm directed against epitopes within Rev, including the nuclear export and nuclear localization domains. These results suggested that the epitope specificity of high- and moderate-avidity CTLm was an important determinant for disease outcome in the EIAV-infected horses examined

  14. Long-term effect of a four-drugs induction regimen for patients with high baseline viral load

    OpenAIRE

    Maggiolo, Franco; Masini,Giulia; Astuti, Noemi; Di Filippo, Elisa; Benatti, Simone; Valenti, Daniela; Callegaro, Anna Paola; Rizzi, Marco

    2014-01-01

    Introduction The long-term effects of an intensified induction regimen are unknown. In this pilot, randomized, prospective study we evaluate the effect of a short-term four-drugs induction regimen in patients with high baseline viral load. Methods Naive patients with HIV-RNA>100.000 copies/ml receiving TDF+FTC+EFV+RAL (group ER) for 4 months and were then simplified to TDF+FTC+EFV. Two randomized control groups treated ab-initio with TDF+FTC+EFV (E) or TDF+FTC+RAL (R) were used. Results 19 pa...

  15. Long-term effect of a four-drugs induction regimen for patients with high baseline viral load

    OpenAIRE

    Franco Maggiolo; Giulia Masini; Noemi Astuti; Elisa Di Filippo; Simone Benatti; Daniela Valenti; Anna Paola Callegaro; Marco Rizzi

    2014-01-01

    Introduction: The long-term effects of an intensified induction regimen are unknown. In this pilot, randomized, prospective study we evaluate the effect of a short-term four-drugs induction regimen in patients with high baseline viral load. Methods: Naive patients with HIV-RNA>100.000 copies/ml receiving TDF+FTC+EFV+RAL (group ER) for 4 months and were then simplified to TDF+FTC+EFV. Two randomized control groups treated ab-initio with TDF+FTC+EFV (E) or TDF+FTC+RAL (R) were used. Results: 19...

  16. Genotypes and viral load of hepatitis C virus among persons attending a voluntary counseling and testing center in Ethiopia.

    Science.gov (United States)

    Abreha, Tesfay; Woldeamanuel, Yimtubezinash; Pietsch, Corinna; Maier, Melanie; Asrat, Daniel; Abebe, Almaz; Hailegiorgis, Bereket; Aseffa, Abraham; Liebert, Uwe Gerd

    2011-05-01

    The prevalence of different genotypes of hepatitis C virus (HCV) in Ethiopia is not known. HCV genotypes influence the response to therapy with alpha-interferon alone or in combination with ribavirin. A cross sectional study was conducted on attendees of voluntary counseling and testing center. Serum samples from 1,954 (734 HIV positive and 1,220 HIV negative) individuals were screened for HCV antibody. Active HCV infection was confirmed by quantitative PCR in 18 of the 71 samples with anti-HCV antibodies. The HCV viral load ranged from 39,650 to 9,878,341 IU/ml (median 1,589,631 IU/ml) with no significant difference [χ(2)(17) = 18.00, P = 0.389] between persons positive or negative for HIV. The viral load of HCV was, however, higher in older study subjects (r = 0.80, P = 0.000). HCV genotypes were determined using the VERSANT HCV Genotype Assay (LiPA) and sequence analysis of the NS5b region of the HCV genome. Diverse HCV genotypes were found including genotypes 1, 2, 4, and 5. There was no difference in the distribution regarding the HIV status. As in other parts of the world, genotyping of HCV must be considered whenever HCV is incriminated as a cause of hepatitis. PMID:21351106

  17. The performance of reverse transcriptase assay for the estimation of the plasma viral load in HIV-1 and HIV-2 infections.

    Science.gov (United States)

    Padaki, Priyadarshini A; Sachithanandham, Jaiprasath; Isaac, Rita; Ramalingam, Veena V; Abraham, Ooriapadickal C; Pulimood, Susanne A; Kannangai, Rajesh

    2016-06-01

    Viral load testing for human immunodeficiency virus 1 (HIV-1) in resource-poor settings continues to be a challenge. Although antiretroviral therapy (ART) is being made available in developing countries, monitoring of viral load is not being done on a regular basis. The purpose of this study was to assess the utility of Cavidi version 3.0, which measures the plasma reverse transcriptase (RT) activity and compare its performance with molecular HIV viral load assays. In all, 125 HIV-1 and 13 HIV-2 positive samples were analyzed. The overall sensitivity of the assay was 86.8% and 94.1% for viral load >1000 copies/ml measured by Qiagen Artus HIV-1 RG RT PCR and Abbott RealTime HIV-1 PCR assays, respectively. Compared with the routine molecular viral load assays, Cavidi version 3.0 is inexpensive, user-friendly, the expenditure on infrastructure is minimal, and it can be used for monitoring of both HIV types. PMID:26654354

  18. The Rhesus Rhadinovirus CD200 Homologue Affects Immune Responses and Viral Loads during In Vivo Infection

    OpenAIRE

    Estep, Ryan D.; Rawlings, Stephanie D.; Li, Helen; Manoharan, Minsha; Blaine, Elizabeth T.; O'Connor, Megan A.; Messaoudi, Ilhem; Axthelm, Michael K.; Wong, Scott W.

    2014-01-01

    Rhesus macaque rhadinovirus (RRV) is a gammaherpesvirus of rhesus macaque (RM) monkeys that is closely related to human herpesvirus 8 (HHV-8)/Kaposi's Sarcoma-associated herpesvirus (KSHV), and it is capable of inducing diseases in simian immunodeficiency virus (SIV)-infected RM that are similar to those seen in humans coinfected with HIV and HHV-8. Both HHV-8 and RRV encode viral CD200 (vCD200) molecules that are homologues of cellular CD200, a membrane glycoprotein that regulates immune res...

  19. 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...... diseases characterized by defective mucus clearance have resulted in a variety of therapies, which might be able to enhance clearance from the lungs. In addition, ways to study in vivo mucociliary clearance in humans have been developed. This can be used as a means to assess the effect of different...... 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, and...

  20. 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

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

    Directory of Open Access Journals (Sweden)

    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

  2. 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

  3. Viral Load, Integration and Methylation of E2BS3 and 4 in Human Papilloma Virus (HPV) 16-Positive Vaginal and Vulvar Carcinomas

    OpenAIRE

    Lillsunde Larsson, Gabriella; Helenius, Gisela; SORBE, BENGT; Karlsson, Mats G

    2014-01-01

    Objective To investigate if viral load, integration and methylation of E2BS3 and 4 represent different ways of tumor transformation in vaginal and vulvar carcinoma and to elucidate its clinical impact. Methods Fifty-seven samples, positive for HPV16, were selected for the study. Detection of viral load was made with realtime-PCR using copy numbers of E6 and integration was calculated from comparing E2 to E6-copies. Methylation of E2BS3 and 4 was analysed using bisulphite treatment of tumor DN...

  4. Association between Virus-Specific T-Cell Responses and Plasma Viral Load in Human Immunodeficiency Virus Type 1 Subtype C Infection

    OpenAIRE

    Novitsky, Vladimir A.; Gilbert, P; T. Peter; McLane, Mary Frances; Gaolekwe, S.; Rybak, N.; Thior, Ibou; Ndung, T.; Marlink, Richard G.; Lee, Tae Ho; Essex, Myron Elmer

    2003-01-01

    Virus-specific T-cell immune responses are important in restraint of human immunodeficiency virus type 1 (HIV-1) replication and control of disease. Plasma viral load is a key determinant of disease progression and infectiousness in HIV infection. Although HIV-1 subtype C (HIV-1C) is the predominant virus in the AIDS epidemic worldwide, the relationship between HIV-1C-specific T-cell immune responses and plasma viral load has not been elucidated. In the present study we address (i) the associ...

  5. 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.

  6. Comparing HBV Viral Load in Serum, Cerumen, and Saliva and Correlation With HBeAg Serum Status in Patients With Chronic Hepatitis B Infection

    Science.gov (United States)

    Gholami Parizad, Elaheh; Gholami Parizad, Eskandar; Khosravi, Afra; Amraei, Mansour; Valizadeh, Azar; Davoudian, Abdoullah

    2016-01-01

    Background Hepatitis B is a disease that is prevalent worldwide and is responsible for 10% of the deaths that occur every year. The virus persists in 5% of infected adults and 90% of infected children and can cause chronic hepatitis. In addition to blood, the virus may also be present in other secretions. Transmission through saliva, sexual fluids, and urine has also been confirmed. Objectives The main aim of this study was to compare viral DNA copies in the serum, cerumen, and saliva of patients with HBeAg levels in their sera. Patients and Methods This was a cross-sectional study and subjects were selected by non-randomized methods. Serum, cerumen, and saliva samples were collected from 50 patients who were diagnosed with chronic hepatitis B about a year prior to the study. Enzyme-linked immunosorbent assay (ELISA) was performed to determine the presence of HBsAg and HBeAg in the gathered specimens. Viral DNA was extracted from specimens by using a Qiagen kit. The number of viral DNA copies was determined using a real-time polymerase chain reaction (PCR) assay. The study was performed in Ilam province in western Iran. Results Twenty-eight percent of the patients were HBeAg positive. The average number of viral copies in serum, cerumen, and saliva was higher in women than in men, and a significant correlation was observed between the gender and average viral copies. However, no significant correlation was observed between viral copies present in the serum and cerumen with the age and gender of patients. In addition, no correlation was observed between serum HBeAg and viral copies present in serum, cerumen, and saliva. The correlation analysis confirmed a direct and definite correlation between viral DNA loads in the patients’ serum and cerumen. Conclusions A significant direct correlation was observed between the viral DNA copies present in patients’ cerumen and serum. However, the correlation between saliva viral load with serum and cerumen viral load was

  7. Targeting of conserved gag-epitopes in early HIV infection is associated with lower plasma viral load and slower CD4+ T cell depletion

    DEFF Research Database (Denmark)

    Perez, Carina L.; Milush, Jeffrey M.; Buggert, Marcus;

    2013-01-01

    epitopes had a significantly lower median viral load over time compared to patients with responses targeting a variable epitope (0.63 log10 difference). Furthermore, the rate of CD4+ T cell decline was slower for subjects targeting a conserved epitope (0.85% per month) compared to subjects targeting a...

  8. 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...... collaboration study. METHODS: A total of 158 385 pairs of consecutive viral load and CD4(+) cell count simultaneously measured from 34 384 ART-naive individuals in the COHERE database were analysed. Annual changes and factors associated with these changes were estimated using generalized estimating equations...... (95% CI) CD4(+) cell count change was -78.0 (-80.1 to -76.0) cell/μl per year and it was strongly associated with a higher current viral load: for every 1 log10 copies/ml higher, CD4(+) cell count declined by an additional 37.6 cells/μl per year (P < 0.001). Current viral load was a stronger predictor...

  9. A Prospective Study of Intimate Partner Violence as a Risk Factor for Detectable Plasma Viral Load in HIV-Positive Women Engaged in Transactional Sex in Mombasa, Kenya.

    Science.gov (United States)

    Wilson, Kate S; Wanje, George; Yuhas, Krista; Simoni, Jane M; Masese, Linnet; Vander Stoep, Ann; Jaoko, Walter; Hughes, James P; Richardson, Barbra A; Scott McClelland, R

    2016-09-01

    We conducted a prospective cohort study to evaluate intimate partner violence (IPV) as a risk factor for detectable plasma viral load in HIV-positive female sex workers (FSWs) on antiretroviral therapy (ART) in Kenya. IPV in the past year was defined as ≥1 act of physical, sexual, or emotional violence by the index partner (i.e. boyfriend/husband). The primary outcome was detectable viral load (≥180 copies/ml). In-depth interviews and focus groups were included to contextualize results. Analyses included 195 women (570 visits). Unexpectedly, IPV was associated with significantly lower risk of detectable viral load (adjusted relative risk 0.21, 95 % CI 0.05-0.84, p-value = 0.02). Qualitative findings revealed that women valued emotional and financial support from index partners, despite IPV. IPV was not a major barrier to ART adherence. The observed association between IPV and lower risk of detectable viral load in FSWs may be due to unmeasured personal and relationship factors, warranting further research. PMID:27142058

  10. Comparative Evaluation of a Commercially Available Automated System for Extraction of Viral DNA from Whole Blood: Application to Monitoring of Epstein-Barr Virus and Cytomegalovirus Load

    OpenAIRE

    Pillet, Sylvie; Bourlet, Thomas; Pozzetto, Bruno

    2009-01-01

    The NucliSENS easyMAG automated system was compared to the column-based Qiagen method for Epstein-Barr virus (EBV) or cytomegalovirus (CMV) DNA extraction from whole blood before viral load determination using the corresponding R-gene amplification kits. Both extraction techniques exhibited a total agreement of 81.3% for EBV and 87.2% for CMV.

  11. 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; Holst, Peter J

    2009-01-01

    -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...

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

    NARCIS (Netherlands)

    Mocroft, A.; Phillips, A.N.; Gatell, J.; Horban, A.; Ledergerber, B.; Zilmer, K.; Jevtovic, D.; Maltez, F.; Podlekareva, D.; Lundgren, J.D.; Burger, D.M.

    2013-01-01

    BACKGROUND: 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 stud

  13. Dynamic Ground Clearance

    OpenAIRE

    Hamache, Violette

    2013-01-01

    The purpose of this work is to develop a test method which will consider the variation of the ground clearance when driving, the so-called dynamic ground clearance. This has been done through the analysis of a specific application: the tractors in grain used in Brazil. Series of real life tests are run in order to obtain data on the tire compressions and the suspension travels. The tractor used is a 6x4 and is loaded with a trailer. When investigating critical cases, the minimum dynamic groun...

  14. 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

  15. 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

  16. Long-term effect of a four-drugs induction regimen for patients with high baseline viral load

    Directory of Open Access Journals (Sweden)

    Franco Maggiolo

    2014-11-01

    Full Text Available Introduction: The long-term effects of an intensified induction regimen are unknown. In this pilot, randomized, prospective study we evaluate the effect of a short-term four-drugs induction regimen in patients with high baseline viral load. Methods: Naive patients with HIV-RNA>100.000 copies/ml receiving TDF+FTC+EFV+RAL (group ER for 4 months and were then simplified to TDF+FTC+EFV. Two randomized control groups treated ab-initio with TDF+FTC+EFV (E or TDF+FTC+RAL (R were used. Results: 19 patients with a mean age of 38 years and mean baseline CD4 count of 334 (SD 216 cells/mcL and HIV-RNA of 5.47 log (SD 0.32 copies/mL were enrolled. No baseline significant difference was observed among groups. Early HIV-RNA reduction was significantly higher in ER compared to the other groups from week 1 to week 4 (P from 0.026 to 0.003 (figure 1, thereafter HIV-RNA values were comparable among the groups. At week 96, all patients had an HIV-RNA < 50 copies/mL, however only patients in the ER group had in all cases an HIV-RNA level < 3 copies/mL with a statistically significant difference compared to E (60%; P=0.038 and R (50%; P=0.020. At 96 weeks, CD4 cell median counts were 765 cells/mcL for ER, 600 cells/mcL for E and 771 for R (P=0.16, however patients in the ER group presented a lower proportion of activated CD4+CD38+HLADR+ cells (1.9% versus 3.9 and 3.8% and CD8+CD38+HLADR+ cells (10.3% versus 16.8 and 16.5% and a significantly better CD4/CD8 ratio (0.98 versus 0.53 and 0.61; P=0.03. Conclusions: A four-drug regimen in naive patients with high pre-therapy viral load improves early virologic response. A quick drop of HIV-RNA seems to correlate with a sustained virologic response. Although limited in time (four months, the four-drug regimens correlates with an improved immunological response as measured by the CD4/CD8 ratio or the percentage of activated CD4+ and CD8+ cells. The reasons why this happens deserve further studies. This study highlights the

  17. Diagnostic values for the viral load in peripheral blood mononuclear cells of patients with chronic active Epstein-Barr virus disease.

    Science.gov (United States)

    Ito, Yoshinori; Suzuki, Michio; Kawada, Jun-Ichi; Kimura, Hiroshi

    2016-04-01

    Chronic active Epstein-Barr virus disease (CAEBV) is a distinct EBV-associated lymphoproliferative disease with a poor prognosis. Although the viral load in blood samples has been widely used for diagnosing CAEBV, well-defined viral load thresholds to guide clinicians are currently lacking. The aim of the present study was to determine standardized diagnostic values for EBV load in blood samples of CAEBV patients using the World Health Organization international standard for reporting. Levels of EBV DNA in 103 peripheral blood mononuclear cells (PBMCs) and 95 plasma/serum samples from 107 cases with CAEBV were quantified and expressed in international units. Receiver operating characteristic curves were analyzed to assess the most appropriate cut-off values for levels of EBV DNA to distinguish CAEBV from EBV-associated infectious mononucleosis (IM) and controls with past EBV infection. Levels of EBV DNA in PBMCs were significantly higher in the CAEBV group (median, 10(4.2) IU/μgDNA) compared to the IM (median, 10(2.1) IU/μgDNA) and control groups. An inconsistent qualitative result was seen in 13 of 86 CAEBV patients; in these, EBV-DNA was positive in PBMCs, but negative in plasma. Diagnostic cut-off values for viral load in PBMCs from CAEBV patients, as compared to those of healthy controls and IM patients, were 10(2.0) IU/μgDNA and 10(3.2) IU/μgDNA, respectively. For diagnostic purposes, the viral load of PBMCs was better than of plasma/serum. A diagnostic cut-off EBV load for CAEBV may be useful for the management of CAEBV patients. PMID:26712582

  18. THE ROLE OF DISEASE STAGE, PLASMA VIRAL LOAD AND Tregs ON AUTO-ANTIBODY PRODUCTION IN THE SIV INFECTED NON-HUMAN PRIMATES1

    OpenAIRE

    Ansari, A; Pereira, Lara E.; Ann E Mayne; Onlamoon, Nattawat; Pattanapanyasat, Kovit; Mori, Kazuyasu; Villinger, F.

    2007-01-01

    Auto-antibodies appear in the sera of rhesus macaques following SIV infection. The present study was conducted to examine the role of viral load, anti-viral chemotherapy and stage of disease on the titers of such auto-antibodies and the spectrum of auto-antigens that become the target of such auto-immune responses. In addition, the role of regulatory T cells (Tregs) was also examined. Results of these studies showed that the highest auto-antibody titers were noted in animals with lower relati...

  19. Some Novel Insights on HPV16 Related Cervical Cancer Pathogenesis Based on Analyses of LCR Methylation, Viral Load, E7 and E2/E4 Expressions

    OpenAIRE

    Das Ghosh, Damayanti; Bhattacharjee, Bornali; Sen, Shrinka; Premi, Laikangbam; Mukhopadhyay, Indranil; Chowdhury, Rahul Roy; Roy, Sudipta; Sengupta, Sharmila

    2012-01-01

    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

  20. 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

  1. Viral hijacking of a replicative helicase loader and its implications for helicase loading control and phage replication

    Science.gov (United States)

    Hood, Iris V; Berger, James M

    2016-01-01

    Replisome assembly requires the loading of replicative hexameric helicases onto origins by AAA+ ATPases. How loader activity is appropriately controlled remains unclear. Here, we use structural and biochemical analyses to establish how an antimicrobial phage protein interferes with the function of the Staphylococcus aureus replicative helicase loader, DnaI. The viral protein binds to the loader’s AAA+ ATPase domain, allowing binding of the host replicative helicase but impeding loader self-assembly and ATPase activity. Close inspection of the complex highlights an unexpected locus for the binding of an interdomain linker element in DnaI/DnaC-family proteins. We find that the inhibitor protein is genetically coupled to a phage-encoded homolog of the bacterial helicase loader, which we show binds to the host helicase but not to the inhibitor itself. These findings establish a new approach by which viruses can hijack host replication processes and explain how loader activity is internally regulated to prevent aberrant auto-association. DOI: http://dx.doi.org/10.7554/eLife.14158.001 PMID:27244442

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

    Directory of Open Access Journals (Sweden)

    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.

  3. Scale-up of Routine Viral Load Testing in Resource-Poor Settings: Current and Future Implementation Challenges.

    Science.gov (United States)

    Roberts, Teri; Cohn, Jennifer; Bonner, Kimberly; Hargreaves, Sally

    2016-04-15

    Despite immense progress in antiretroviral therapy (ART) scale-up, many people still lack access to basic standards of care, with our ability to meet the Joint United Nations Programme on HIV/AIDS 90-90-90 treatment targets for HIV/AIDS dependent on dramatic improvements in diagnostics. The World Health Organization recommends routine monitoring of ART effectiveness using viral load (VL) testing at 6 months and every 12 months, to monitor treatment adherence and minimize failure, and will publish its VL toolkit later this year. However, the cost and complexity of VL is preventing scale-up beyond developed countries and there is a lack of awareness among clinicians as to the long-term patient benefits and its role in prolonging the longevity of treatment programs. With developments in this diagnostic field rapidly evolving-including the recent improvements for accurately using dried blood spots and the imminent appearance to the market of point-of-care technologies offering decentralized diagnosis-we describe current barriers to VL testing in resource-limited settings. Effective scale-up can be achieved through health system and laboratory system strengthening and test price reductions, as well as tackling multiple programmatic and funding challenges. PMID:26743094

  4. 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.

  5. 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

  6. 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.

    Directory of Open Access Journals (Sweden)

    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.

  7. 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; Ring-Larsen, H.; Krarup, H. B.

    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...... hepatitis C viral load as well as oxidative and antioxidant markers in patients with hepatitis C virus infection. The participants received a daily dose of ascorbic acid (500 mg), D-alpha-tocopherol (9451 U) and selenium (200 mu g) or placebo tablets for 6 months. Results Twenty-three patients were included...... aminotransferase and logo-transformed plasma hepatitis C virus-RNA between the groups or changes from the baseline at any time. No consistent differences between groups or changes from the baseline with respect to erythrocyte activities of antioxidative enzymes (glutathione reductase, superoxide dismutase and...

  8. 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.

  9. Twelve-Month Antiretroviral Therapy Suppresses Plasma and Genital Viral Loads but Fails to Alter Genital Levels of Cytokines, in a Cohort of HIV-Infected Rwandan Women

    OpenAIRE

    Ondoa, Pascale; Gautam, Raju; Rusine, John; Lutter, Rene; Jurriaans, Suzanne; Kootstra, Neeltje; Karita, Etienne; Wijgert, Janneke

    2015-01-01

    Background Genital viral load (GVL) is the main determinant of sexual transmission of human immune-deficiency virus (HIV). The effect of antiretroviral therapy (ART) on local cervico-vaginal immunological factors associated with GVL is poorly described. We aimed to identify the risk factors of detectable GVL, and the impact of ART on HIV genital shedding and its correlates in a cohort of HIV-infected women, attending HIV care in Kigali, Rwanda. Materials and Methods All participants were eval...

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

    OpenAIRE

    Kawaguchi, Takumi; Torimura, Takuji; Takata, Akio; Satomi, Susumu; Sata, Michio

    2012-01-01

    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...

  11. 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....

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

    Directory of Open Access Journals (Sweden)

    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.

  13. Vaccination with Brucella abortus recombinant in vivo-induced antigens reduces bacterial load and promotes clearance in a mouse model for infection.

    Directory of Open Access Journals (Sweden)

    Jake E Lowry

    Full Text Available Current vaccines used for the prevention of brucellosis are ineffective in inducing protective immunity in animals that are chronically infected with Brucella abortus, such as elk. Using a gene discovery approach, in vivo-induced antigen technology (IVIAT on B. abortus, we previously identified ten loci that encode products up-regulated during infection in elk and consequently may play a role in virulence. In our present study, five of the loci (D15, 0187, VirJ, Mdh, AfuA were selected for further characterization and compared with three additional antigens with virulence potential (Hia, PrpA, MltA. All eight genes were PCR-amplified from B. abortus and cloned into E. coli. The recombinant products were then expressed, purified, adjuvanted, and delivered subcutaneously to BALB/c mice. After primary immunization and two boosts, mice were challenged i.p. with 5 x 10⁴ CFU of B. abortus strain 19. Spleens from challenged animals were harvested and bacterial loads determined by colony count at various time points. While vaccination with four of the eight individual proteins appeared to have some effect on clearance kinetics, mice vaccinated with recombinant Mdh displayed the most significant reduction in bacterial colonization. Furthermore, mice immunized with Mdh maintained higher levels of IFN-γ in spleens compared to other treatment groups. Collectively, our in vivo data gathered from the S19 murine colonization model suggest that vaccination with at least three of the IVIAT antigens conferred an enhanced ability of the host to respond to infection, reinforcing the utility of this methodology for the identification of potential vaccine candidates against brucellosis. Mechanisms for immunity to one protein, Mdh, require further in vitro exploration and evaluation against wild-type B. abortus challenge in mice, as well as other hosts. Additional studies are being undertaken to clarify the role of Mdh and other IVI antigens in B. abortus virulence

  14. Vaccination with Brucella abortus recombinant in vivo-induced antigens reduces bacterial load and promotes clearance in a mouse model for infection.

    Science.gov (United States)

    Lowry, Jake E; Isaak, Dale D; Leonhardt, Jack A; Vernati, Giulia; Pate, Jessie C; Andrews, Gerard P

    2011-01-01

    Current vaccines used for the prevention of brucellosis are ineffective in inducing protective immunity in animals that are chronically infected with Brucella abortus, such as elk. Using a gene discovery approach, in vivo-induced antigen technology (IVIAT) on B. abortus, we previously identified ten loci that encode products up-regulated during infection in elk and consequently may play a role in virulence. In our present study, five of the loci (D15, 0187, VirJ, Mdh, AfuA) were selected for further characterization and compared with three additional antigens with virulence potential (Hia, PrpA, MltA). All eight genes were PCR-amplified from B. abortus and cloned into E. coli. The recombinant products were then expressed, purified, adjuvanted, and delivered subcutaneously to BALB/c mice. After primary immunization and two boosts, mice were challenged i.p. with 5 x 10⁴ CFU of B. abortus strain 19. Spleens from challenged animals were harvested and bacterial loads determined by colony count at various time points. While vaccination with four of the eight individual proteins appeared to have some effect on clearance kinetics, mice vaccinated with recombinant Mdh displayed the most significant reduction in bacterial colonization. Furthermore, mice immunized with Mdh maintained higher levels of IFN-γ in spleens compared to other treatment groups. Collectively, our in vivo data gathered from the S19 murine colonization model suggest that vaccination with at least three of the IVIAT antigens conferred an enhanced ability of the host to respond to infection, reinforcing the utility of this methodology for the identification of potential vaccine candidates against brucellosis. Mechanisms for immunity to one protein, Mdh, require further in vitro exploration and evaluation against wild-type B. abortus challenge in mice, as well as other hosts. Additional studies are being undertaken to clarify the role of Mdh and other IVI antigens in B. abortus virulence and induction of

  15. Carga viral vaginal de HIV em mulheres brasileiras infectadas pelo HIV HIV vaginal viral load in Brazilian HIV-infected women

    OpenAIRE

    Angela Campos; Eliana Amaral; José Eduardo Levi; Priscila Portugal; Marina Villarroel; Karina C. Bezerra; Marcos T. Nolasco da Silva; Sirlei Siani Morais

    2008-01-01

    OBJETIVO: Avaliar os fatores associados à presença de RNA-HIV na vagina. MÉTODOS: Estudo de corte transversal, em mulheres infectadas por HIV, excluindo-se aquelas com antecedente de histerectomia, as em uso de medicações vaginais nas últimas 48 horas, as que se referiram à relação sexual desprotegida há menos de 72 horas, as gestantes e aquelas com sangramento genital. Após consentimento, coletou-se amostra sanguínea para contagem de linfócitos T CD4 e carga viral plasmática de HIV, além de ...

  16. 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

  17. Albuminuria Is Associated with Traditional Cardiovascular Risk Factors and Viral Load in HIV-Infected Patients in Rural South Africa.

    Directory of Open Access Journals (Sweden)

    G Emerens Wensink

    Full Text Available As life expectancy improves among Human Immunodeficiency Virus (HIV patients, renal and cardiovascular diseases are increasingly prevalent in this population. Renal and cardiovascular disease are mutual risk factors and are characterized by albuminuria. Understanding the interactions between HIV, cardiovascular risk factors and renal disease is the first step in tackling this new therapeutic frontier in HIV.In a rural primary health care centre, 903 HIV-infected adult patients were randomly selected and data on HIV-infection and cardiovascular risk factors were collected. Glomerular filtration rate (eGFR was estimated. Albuminuria was defined as an Albumin-Creatinine-Ratio above 30 mg/g. Multivariate logistic regression analysis was used to analyse albuminuria and demographic, clinical and HIV-associated variables.The study population consisted of 903 HIV-infected patients, with a median age of 40 years (Inter-Quartile Range (IQR 34-48 years, and included 625 (69% women. The median duration since HIV diagnosis was 26 months (IQR 12-58 months and 787 (87% received antiretroviral therapy. Thirty-six (4% of the subjects were shown to have diabetes and 205 (23% hypertension. In the cohort, 21% had albuminuria and 2% an eGFR <60 mL/min/1.73m2. Albuminuria was associated with hypertension (adjusted odds ratio (aOR 1.59; 95% confidence interval (CI 1.05-2.41; p<0.05, total cholesterol (aOR 1.31; 95% CI 1.11-1.54; p<0.05, eGFR (aOR 0.98; 95% CI 0.97-0.99; p<0.001 and detectable viral load (aOR 2.74; 95% CI 1.56-4.79; p<0.001. Hypertension was undertreated: 78% were not receiving treatment, while another 11% were inadequately treated. No patients were receiving lipid-lowering medication.Glomerular filtration rate was well conserved, while albuminuria was common amongst HIV-infected patients in rural South Africa. Both cardiovascular and HIV-specific variables were associated with albuminuria. Improved cardiovascular risk prevention as well as adequate

  18. 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.

  19. Relationship between changes of blood HBV-DNA viral load and serum liver fibrosis markers (HA, LN, IV-C, PCIII) levels in patients with chronic hepatitis B

    International Nuclear Information System (INIS)

    Objective: To investigate the relationship between changes of blood HBV DNA viral load and serum liver fibrosis markers levels in patients with chronic hepatitis B. Methods: In 2002, 20 patients with hepatitis B were divided into two groups: Group A treated with antiviral ageat (n=10), Group B not treated.Five years later (2007) the blood viral load (with FQ-PCR) and serum levels of hepatic fibrosis markers (with RIA) were determined in these patients. Results: The average log viral load in serum in the tow groups were 3.56 ± 1.12 (treated group) and 7.76 ± 1.23 respectively with significant difference (P<0.05). In 2002, serum liver fibrosis markers (HA, LN, IV-C, PCIII) levels were about the same in the two groups were (82.72 ± 30.62μg/ml, 71.18 ± 26.71μg/ml, 93.77 ± 69.87μg/ml, 91.4 ± 18.64μg/ml and 79.32 ± 31.34μg/ml, 70.25 ± 28.23)μg/ml, 90.35 ± 67.81μg/ml, 85.77 ± 20.56μg/ml respectively). In 2007, in the treated patients, serum liver fibrosis markers HA, LN, IV-C, PCIII levels were 85.72 ± 29.52μg/ml, 70.18 ± 25.4μg/ml, 94.2 ± 70.92μg/ml, 93.4 ± 19.32μg/ml respectively However, in the non-treated groups, the serum HA, LN, IV-C, PCIII levels were105.67 ± 28.54μg/ml, 97.75 ± 26.25μg/ml, 132 ± 72.13μg/ml, 120.72 ± 19.87μg/ml, being significantly higher than those in the treated group (P<0.05). Conclusion: Effective decrease of the viral load might control the progress of hepatic fibrosis in patients with chronic hepatitis B. (authors)

  20. 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; Ring-Larsen, H.; Krarup, H. B.

    2006-01-01

    hepatitis C viral load as well as oxidative and antioxidant markers in patients with hepatitis C virus infection. The participants received a daily dose of ascorbic acid (500 mg), D-alpha-tocopherol (9451 U) and selenium (200 mu g) or placebo tablets for 6 months. Results Twenty-three patients were included....... During supplementation, the antioxidant group had significantly higher levels of plasma ascorbic acid and a-tocopherol than the placebo group and the activity of erythrocyte glutathione peroxidase had significantly increased from baseline to month 6. No differences were observed in serum alanine...

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

    Directory of Open Access Journals (Sweden)

    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

  2. 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

    Directory of Open Access Journals (Sweden)

    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.

  3. Experimental infection of European flat oyster Ostrea edulis with ostreid herpesvirus 1 microvar (OsHV-1μvar): Mortality, viral load and detection of viral transcripts by in situ hybridization.

    Science.gov (United States)

    López Sanmartín, Monserrat; Power, Deborah M; de la Herrán, Roberto; Navas, José I; Batista, Frederico M

    2016-06-01

    Ostreid herpesvirus 1 (OsHV-1) infections have been reported in several bivalve species. Mortality of Pacific oyster Crassostrea gigas spat has increased considerably in Europe since 2008 linked to the spread of a variant of OsHV-1 called μvar. In the present study we demonstrated that O. edulis juveniles can be infected by OsHV-1μvar when administered as an intramuscular injection. Mortality in the oysters injected with OsHV-1μvar was first detected 4 days after injection and reached 25% mortality at day 10. Moreover, the high viral load observed and the detection of viral transcripts by in situ hybridization in several tissues of dying oysters suggested that OsHV-1μvar was the cause of mortality in the O. edulis juveniles. This is therefore the first study to provide evidence about the pathogenicity of OsHV-1μvar in a species that does not belong to the Crassostrea genus. Additionally, we present a novel method to detect OsHV-1 transcripts in infected individuals' using in situ hybridization. PMID:26945849

  4. Viral Load and a Locus on Chromosome 11 Affect the Late Clinical Disease Caused by Theiler’s Virus

    OpenAIRE

    Aubagnac, Stéphanie; Brahic, Michel; Bureau, Jean-François

    1999-01-01

    Theiler’s virus causes a persistent infection and a demyelinating disease of mice which is a model for multiple sclerosis. Susceptibility to viral persistence maps to several loci, including the interferon gamma locus. Inactivating the gene coding for the interferon gamma receptor makes 129/Sv mice susceptible to persistent infection and clinical disease, whereas inactivating the interferon gamma gene makes C57BL/6 mice susceptible to persistent infection but not to clinical disease. This dif...

  5. Detection of Human Bocavirus mRNA in Respiratory Secretions Correlates with High Viral Load and Concurrent Diarrhea

    OpenAIRE

    Proença-Modena, José Luiz; Gagliardi, Talita Bianca; Escremim de Paula, Flávia; Iwamoto, Marisa Akiko; Criado, Miriã Ferreira; Camara, Ataíde A.; Acrani, Gustavo Olszanski; Cintra, Otávio Augusto Leite; Cervi, Maria Célia; de Paula Arruda, Luisa Karla; Arruda, Eurico

    2011-01-01

    Human bocavirus (HBoV) is a parvovirus recently identified in association with acute respiratory infections (ARI). Despite its worldwide occurrence, little is known on the pathogenesis of HBoV infections. In addition, few systematic studies of HBoV in ARI have been conducted in Latin America. Therefore, in order to test whether active viral replication of human bocavirus is associated with respiratory diseases and to understand the clinical impact of this virus in patients with these diseases...

  6. Protective efficacy of VP1-specific neutralizing antibody associated with a reduction of viral load and pro-inflammatory cytokines in human SCARB2-transgenic mice.

    Directory of Open Access Journals (Sweden)

    Hsuen-Wen Chang

    Full Text Available Hand-foot-mouth diseases (HFMD caused by enterovirus 71 (EV71 and coxsackievirus 16 (CVA16 in children have now become a severe public health issue in the Asian-Pacific region. Recently we have successfully developed transgenic mice expressing human scavenger receptor class B member 2 (hSCARB2, a receptor of EV71 and CVA16 as an animal model for evaluating the pathogenesis of enterovirus infections. In this study, hSCARB2-transgenic mice were used to investigate the efficacy conferred by a previously described EV71 neutralizing antibody, N3. A single injection of N3 effectively inhibited the HFMD-like skin scurfs in mice pre-infected with clinical isolate of EV71 E59 (B4 genotype or prevented severe limb paralysis and death in mice pre-inoculated with 5746 (C2 genotype. This protection was correlated with remarkable reduction of viral loads in the brain, spinal cord and limb muscles. Accumulated viral loads and the associated pro-inflammatory cytokines were all reduced. The protective efficacy of N3 was not observed in animals challenged with CVA16. This could be due to dissimilarity sequences of the neutralizing epitope found in CVA16. These results indicate N3 could be useful in treating severe EV71 infections and the hSCARB2-transgenic mouse could be used to evaluate the protective efficacy of potential anti-enterovirus agent candidates.

  7. Exposure to environmental stressors result in increased viral load and further reduction of production parameters in pigs experimentally infected with PCV2b.

    Science.gov (United States)

    Patterson, Robert; Nevel, Amanda; Diaz, Adriana V; Martineau, Henny M; Demmers, Theo; Browne, Christopher; Mavrommatis, Bettina; Werling, Dirk

    2015-06-12

    Porcine circovirus type 2 (PCV2) has been identified as the essential, but not sole, underlying infectious component for PCV-associated diseases (PCVAD). Several co-factors have been suggested to convert an infection with PCV2 into the clinical signs of PCVAD, including co-infection with a secondary pathogen and the genetic background of the pig. In the present study, we investigated the role of environmental stressors in the form of changes in environmental temperature and increased stocking-density on viral load in serum and tissue, average daily weight gain (ADG) and food conversion rate (FCR) of pigs experimentally infected with a defined PCV2b strain over an eight week period. These stressors were identified recently as risk factors leading to the occurrence of severe PCVAD on a farm level. In the current study, PCV2-free pigs were housed in separate, environmentally controlled rooms, and the experiment was performed in a 2×2 factorial design. In general, PCV2b infection reduced ADG and increased FCR, and these were further impacted on by the environmental stressors. Furthermore, all stressors led to an increased viral load in serum and tissue as assessed by qPCR, although levels did not reach statistical significance. Our data suggest that there is no need for an additional pathogen to develop PCVAD in conventional status pigs, and growth retardation and clinical signs can be induced in PCV2 infected pigs that are exposed to environmental stressors alone. PMID:25866129

  8. 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

    Directory of Open Access Journals (Sweden)

    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.

  9. PNPLA 3 I148M genetic variant associates with insulin resistance and baseline viral load in HCV genotype 2 but not in genotype 3 infection

    Directory of Open Access Journals (Sweden)

    Rembeck Karolina

    2012-09-01

    Full Text Available Abstract Background Hepatic steatosis in HCV patients has been postulated as a risk factor associated with a higher frequency of fibrosis and cirrhosis. A single genetic variant, PNPLA3 I148M, has been widely associated with increased hepatic steatosis. Previous studies of the PNPLA3 I148M sequence variant in HCV infected individuals have reported an association between this variant and prevalence of steatosis, fibrosis, and cirrhosis. To evaluate the impact of PNPLA3 I148M variant on metabolic traits and treatment response in HCV genotype 2 and 3 infected patients. Methods Three hundred and eighty-two treatment naïve HCV genotype 2 or 3 infected patients were included in a phase III, open label, randomized, multicenter, investigator-initiated trial (the NORDynamIC study, in which pretreatment liver biopsies were mandatory. PNPLA3I148M genotyping was performed in a total of 359 Caucasian patients. Results In HCV genotype 2 infected patients carrying the PNPLA3 148M allele, there was significantly increased insulin resistance (P = 0.023 and lower viral load (P = 0.005 at baseline as well as the first seven days of antiviral treatment. These results were not observed in HCV genotype 3 infected patients. Conclusions Our results suggest a possible association between the PNPLA3 148M allele and insulin resistance as well as baseline viral load in HCV genotype 2, but not in genotype 3.

  10. Comparison of prevalence, viral load, physical status and expression of human papillomavirus-16, -18 and -58 in esophageal and cervical cancer: a case-control study

    Directory of Open Access Journals (Sweden)

    Shen Zhongying

    2010-11-01

    Full Text Available Abstract Background Human papillomavirus (HPV infection is a major risk factor for the development of nearly all cases of cervical cancer worldwide. The presence of HPV DNA in cases of esophageal squamous-cell carcinoma (ESCC has been reported repeatedly from Shantou, China, and other regions with a high incidence of esophageal carcinoma (EC. However, unlike in cervical squamous-cell carcinoma (CSCC, in ESCC, the characteristics of HPV are unclear. Thus, the role of high-risk HPV types in the carcinogenesis of ESCC remains uncertain. Methods Seventy cases of ESCC with 60 controls and 39 cases of CSCC with 54 controls collected from patients in Shantou region in China were compared for the distributions of HPV-16, -18 and -58; viral load; and viral integration using real-time PCR assay and HPV-16 expression using immunostaining. Results The detection rates and viral loads of HR-HPV infection were significantly lower in ESCC than in CSCC (50.0% vs. 79.48%, P = 0.005; 2.55 ± 3.19 vs. 361.29 ± 441.75, P = 0.002, respectively. The combined integration level of HPV-16, -18 and -58 was slightly lower in ESCC than in CSCC (P = 0.022. HPV-16 expression was detected in 59.26% of ESCC tissue and significantly associated with tumour grade (P = 0.027. Conclusions High levels of HR-HPV expression and integration may be an indicator of the risk of ESCC, at least for patients in the Shantou region of China. However, a relatively low HPV copy number and infection rate in ESCC is unlikely to play an essential a role in the carcinogenesis of ESCC as in cervical cancer. Factors other than HR-HPV infection may contribute to the carcinogenesis of ESCC.

  11. Comparison of prevalence, viral load, physical status and expression of human papillomavirus-16, -18 and -58 in esophageal and cervical cancer: a case-control study

    International Nuclear Information System (INIS)

    Human papillomavirus (HPV) infection is a major risk factor for the development of nearly all cases of cervical cancer worldwide. The presence of HPV DNA in cases of esophageal squamous-cell carcinoma (ESCC) has been reported repeatedly from Shantou, China, and other regions with a high incidence of esophageal carcinoma (EC). However, unlike in cervical squamous-cell carcinoma (CSCC), in ESCC, the characteristics of HPV are unclear. Thus, the role of high-risk HPV types in the carcinogenesis of ESCC remains uncertain. Seventy cases of ESCC with 60 controls and 39 cases of CSCC with 54 controls collected from patients in Shantou region in China were compared for the distributions of HPV-16, -18 and -58; viral load; and viral integration using real-time PCR assay and HPV-16 expression using immunostaining. The detection rates and viral loads of HR-HPV infection were significantly lower in ESCC than in CSCC (50.0% vs. 79.48%, P = 0.005; 2.55 ± 3.19 vs. 361.29 ± 441.75, P = 0.002, respectively). The combined integration level of HPV-16, -18 and -58 was slightly lower in ESCC than in CSCC (P = 0.022). HPV-16 expression was detected in 59.26% of ESCC tissue and significantly associated with tumour grade (P = 0.027). High levels of HR-HPV expression and integration may be an indicator of the risk of ESCC, at least for patients in the Shantou region of China. However, a relatively low HPV copy number and infection rate in ESCC is unlikely to play an essential a role in the carcinogenesis of ESCC as in cervical cancer. Factors other than HR-HPV infection may contribute to the carcinogenesis of ESCC

  12. Immunogenetics: Genome-Wide Association of Non-Progressive HIV and Viral Load Control: HLA Genes and Beyond

    OpenAIRE

    Limou, Sophie; Zagury, Jean-François

    2013-01-01

    Very early after the identification of the human immunodeficiency virus (HIV), host genetics factors were anticipated to play a role in viral control and disease progression. As early as the mid-1990s, candidate gene studies demonstrated a central role for the chemokine co-receptor/ligand (e.g., CCR5) and human leukocyte antigen (HLA) systems. In the last decade, the advent of genome-wide arrays opened a new era for unbiased genetic exploration of the genome and brought big expectations for t...

  13. 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.

  14. Characterizing Class-Specific Exposure-Viral Load Suppression Response of HIV Antiretrovirals Using A Model-Based Meta-Analysis.

    Science.gov (United States)

    Xu, Y; Li, Y F; Zhang, D; Dockendorf, M; Tetteh, E; Rizk, M L; Grobler, J A; Lai, M-T; Gobburu, J; Ankrom, W

    2016-08-01

    We applied model-based meta-analysis of viral suppression as a function of drug exposure and in vitro potency for short-term monotherapy in human immunodeficiency virus type 1 (HIV-1)-infected treatment-naïve patients to set pharmacokinetic targets for development of nonnucleoside reverse transcriptase inhibitors (NNRTIs) and integrase strand transfer inhibitors (InSTIs). We developed class-specific models relating viral load kinetics from monotherapy studies to potency normalized steady-state trough plasma concentrations. These models were integrated with a literature assessment of doses which demonstrated to have long-term efficacy in combination therapy, in order to set steady-state trough concentration targets of 6.17- and 2.15-fold above potency for NNRTIs and InSTIs, respectively. Both the models developed and the pharmacokinetic targets derived can be used to guide compound selection during preclinical development and to predict the dose-response of new antiretrovirals to inform early clinical trial design. PMID:27171172

  15. Twelve-Month Antiretroviral Therapy Suppresses Plasma and Genital Viral Loads but Fails to Alter Genital Levels of Cytokines, in a Cohort of HIV-Infected Rwandan Women.

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    Pascale Ondoa

    Full Text Available Genital viral load (GVL is the main determinant of sexual transmission of human immune-deficiency virus (HIV. The effect of antiretroviral therapy (ART on local cervico-vaginal immunological factors associated with GVL is poorly described. We aimed to identify the risk factors of detectable GVL, and the impact of ART on HIV genital shedding and its correlates in a cohort of HIV-infected women, attending HIV care in Kigali, Rwanda.All participants were evaluated for GVL, plasma viral load (PVL, CD4 count, various sexually-transmitted infections (STIs at baseline and at month 12. Genital concentration of 19 cytokines and mRNA expression of APOBEC3G and BST2, two host HIV restriction factors, were evaluated at baseline in all participants. Cytokine levels were re-assessed at month 12 only in participants eligible for ART at baseline. Risk factors of GVL ≥ 40 copies/mL at baseline and month 12 were assessed using logistic regression. Effect of 12-month ART on various local and systemic immunological parameters was examined using a paired t-test and McNemar as appropriate.96 of the 247 women enrolled in the study were eligible for ART. After 12 months of ART, PVL and GVL decreased to undetectable level in respectively 74 and 88% of treated participants. ART did not affect cytokine levels. HIV genital shedding occurred only when PVL was detectable. At baseline, GVL was independently associated with IL-1β after controlling for PVL, age and N. gonorrhea infection (95% CI 1.32-2.15 and at month 12 with MIP-1β (95% CI 0.96-21.32 after controlling for baseline GVL, PVL and month 12 IL-8.Suppressive ART does not necessarily reduce genital level of immune activation. Minimizing all conditions favoring genital inflammation, including active detection and treatment of STIs, might reduce the risk of HIV transmission as supplement to the provision of potent ART.

  16. Association of HIV infection with distribution and viral load of HPV types in Kenya: a survey with 820 female sex workers

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    Delva Wim

    2010-01-01

    Full Text Available Abstract Background Human papillomavirus (HPV and HIV are each responsible for a considerable burden of disease. Interactions between these infections pose substantial public health challenges, especially where HIV prevalence is high and HPV vaccine coverage low. Methods Between July 2005 and January 2006, a cross-sectional community-based survey in Mombasa, Kenya, enrolled female sex workers using snowball sampling. After interview and a gynaecological examination, blood and cervical cytology samples were taken. Quantitative real-time PCR detected HPV types and viral load measures. Prevalence of high-risk HPV was compared between HIV-infected and -uninfected women, and in women with abnormal cervical cytology, measured using conventional Pap smears. Results Median age of the 820 participants was 28 years (inter-quartile range [IQR] = 24-36 years. One third of women were HIV infected (283/803; 35.2% and these women were y more likely to have abnormal cervical cytology than HIV-negative women (27%, 73/269, versus 8%, 42/503; P P P = 0.98. High-risk HPV types other than 16 and 18 were common in LSIL (74.7%; 56/75 and HSIL (84.6%; 22/26; even higher among HIV-infected women. Conclusions HIV-infected sex workers had almost four-fold higher prevalence of high-risk HPV, raised viral load and more precancerous lesions. HPV 16 and HPV 18, preventable with current vaccines, were associated with cervical disease, though other high-risk types were commoner. HIV-infected sex workers likely contribute disproportionately to HPV transmission dynamics in the general population. Current efforts to prevent HIV and HPV are inadequate. New interventions are required and improved implementation of existing strategies.

  17. Messenger RNA-based therapeutics for brain diseases: An animal study for augmenting clearance of beta-amyloid by intracerebral administration of neprilysin mRNA loaded in polyplex nanomicelles.

    Science.gov (United States)

    Lin, Chin-Yu; Perche, Federico; Ikegami, Masaru; Uchida, Satoshi; Kataoka, Kazunori; Itaka, Keiji

    2016-08-10

    Alzheimer's disease (AD) pathogenesis is considered to be the metabolic imbalance between anabolism and clearance of amyloid-beta (Aβ), and the strategy of breaking the equilibrium between soluble and insoluble forms of Aβ is likely to help prevent the progression of AD. Neprilysin (NEP) plays a major role in the clearance of Aβ in the brain, and its supplementation using viral vectors has shown to decrease Aβ deposition and prevent pathogenic changes in the brain. In this study, we developed a new therapeutic strategy by mRNA-based gene introduction. mRNA has the advantages of negligible risk of random integration into genome and not needing to be transcribed precludes the need for nuclear entry. This allows efficient protein expression in slowly-dividing or non-dividing cells, such as neural cells. We constructed mRNA encoding the mouse NEP protein and evaluated its ability degrade Aβ. In vitro transfection of NEP mRNA to primary neurons exhibited Amyloid Precursor Protein (APP) degradation activity superior to that of NEP encoding plasmid DNA. We then evaluated the in vivo activity of NEP mRNA by intracerebroventricular (i.c.v.) infusion using a cationic polymer-based PEGylated nanocarrier to form polyplex nanomicelles, which have been shown to have a high potential to deliver mRNA to various target tissues and organs. Nanomicelles carrying a GFP-NEP fusion mRNA produced efficient protein expression in a diffuse manner surrounding the ventricular space. An ELISA evaluation revealed that the mRNA infusion significantly augmented NEP level and effectively reduced the concentration of Aβ that had been supplemented in the mouse brain. To the best of our knowledge, this is the first study to demonstrate the therapeutic potential of introducing exogenous mRNA for the treatment of brain diseases, opening the new era of mRNA-based therapeutics. PMID:27282413

  18. Viral load rebound in presumed elite controllers: a small case series of the potential use of non-prescribed HAART in African patients

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    D Brawley

    2012-11-01

    Full Text Available Introduction: HIV elite controllers are rare with an incidence of <1/300 [1]. We report 4 cases of presumed elite control with subsequent viral load rebound possibly due to non-prescribed HAART. Case 1: A 37-year-old African woman trafficked to the UK was diagnosed HIV-positive with viral load (VL <40 copies/mL and CD4 count of 436 cells/cmm. She denied prior diagnosis and was presumed an elite controller until a rise in VL to 26,5205 copies/mL 6 months later (Table 1. A resistance test reported HIV-1 subtype C with a minor protease inhibitor mutation (A71T. It was subsequently disclosed she was given unidentified tablets by traffickers. Case 2: A 31-year-old African woman presented 37 weeks pregnant and was diagnosed HIV-positive with VL 147 copies/mL and CD4 count of 1065 cells/cmm. She denied prior diagnosis, however stated an African doctor visited her ex-partner's home and supplied tablets identified as lopinavir/ritonavir and zidovudine/lamivudine. Clinics in this area were contacted but had no record of this patient. There was a rise in VL with a resistance test reporting HIV-1 subtype C/D with no mutations. Case 3: A 53-year-old African woman presented 6 weeks after a sexual assault in her home country and was diagnosed HIV-positive with VL<40 copies/mL and CD4 count of 609 cells/cmm. She denied prior diagnosis but stated her employers gave her unidentified tablets after the assault. Over 3 months VL increased to 390,751 copies/mL (Table 2. A resistance test reported HIV-1 subtype A with no mutations. Case 4: A 42-year-old African man was diagnosed HIV positive with VL 269 copies/mL and CD4 count of 562 cells/cmm. A resistance test reported HIV-1 subtype B with minor PI and NRTI mutations (L10V and V118L respectively. HIV parameters remained stable until 20 months later with an increase in VL to 1,463,132 copies/mL (Table 3. A resistance test excluded super-infection reporting a similar sequence and no new mutations. Co

  19. Bacterial–viral load and the immune response in stable and exacerbated COPD: significance and therapeutic prospects

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    D’Anna SE

    2016-03-01

    Full Text Available Silvestro Ennio D’Anna,1 Bruno Balbi,2 Francesco Cappello,3,4 Mauro Carone,2 Antonino Di Stefano21Department of Rehabilitation, Cardiorespiratory Unit, Fondazione Istituto G. Giglio di Cefalù, 2Pneumology Unit and Laboratory of Cytoimmunopathology of Heart and Lung, Fondazione Salvatore Maugeri, IRCCS, Veruno (NO and Cassano delle Murge (BA, 3Human Anatomy Section, Department of Experimental Biomedicine and Clinical Neuroscience, University of Palermo, Palermo, Italy; 4Euro-Mediterranean Institute of Science and Technology, Palermo, ItalyAbstract: Chronic obstructive pulmonary disease (COPD is characterized by persistent airflow limitation and an abnormal inflammatory response of the lung. Bacteria and viruses are a major cause of COPD exacerbations and may contribute to COPD progression by perpetuating the inflammatory response in the airways. Bacterial variety diminishes with increasing COPD severity. Respiratory viruses can colonize the lower respiratory tract in stable COPD, altering the respiratory microbiome and facilitating secondary bacterial infections. In this review, we present the most updated information about the role of bacteria and viruses in stable and exacerbated COPD. In our opinion, to optimize therapeutic strategies, the dynamic events involving bacterial–viral infections and related immune response in COPD phenotypes need to be better clarified. Our paper would address these points that we consider of great importance for the clinical management of COPD.Keywords: COPD phenotype, biomarkers, exacerbations, severity of COPD, microbiome

  20. Liver Stiffness Measurement and Biochemical Markers in Senegalese Chronic Hepatitis B Patients with Normal ALT and High Viral Load

    OpenAIRE

    Mbaye, Papa Saliou; Sarr, Anna; Sire, Jean-Marie; Evra, Marie-Louise; Ba, Adama; Daveiga, Jean; Diallo, Aboubakry; Fall, Fatou; Chartier, Loic; Simon, François; Vray, Muriel

    2011-01-01

    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 log10 IU/mL and normal alanine aminotransferase (ALT) values. Methods LSM and liver fibrosis biochemical markers were performed on 225 consecutive...

  1. 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?

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    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.

  2. 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

  3. 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;

    2015-01-01

    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. Duri...

  4. High viral loads despite absence of clinical and pathological findings in cats experimentally infected with feline coronavirus (FCoV) type I and in naturally FCoV-infected cats.

    Science.gov (United States)

    Meli, M; Kipar, A; Müller, C; Jenal, K; Gönczi, E; Borel, N; Gunn-Moore, D; Chalmers, S; Lin, F; Reinacher, M; Lutz, H

    2004-04-01

    Specified pathogen-free cats were naturally infected with FCoV or experimentally infected with FCoV type I. Seroconversion was determined and the course of infection was monitored by measuring the FCoV loads in faeces, whole blood, plasma and/or monocytes. Tissue samples collected at necropsy were examined for viral load and histopathological changes. Experimentally infected animals started shedding virus as soon as 2 days after infection. They generally displayed the highest viral loads in colon, ileum and mesenteric lymph nodes. Seroconversion occurred 3-4 weeks post infection. Naturally infected cats were positive for FCoV antibodies and monocyte-associated FCoV viraemia prior to death. At necropsy, most animals tested positive for viral shedding and FCoV RNA was found in spleen, mesenteric lymph nodes and bone marrow. Both experimentally and naturally infected cats remained clinically healthy. Pathological findings were restricted to generalized lymphatic hyperplasia. These findings demonstrate the presence of systemic FCoV infection with high viral loads in the absence of clinical and pathological signs. PMID:15123151

  5. Viral load kinetics of Zika virus in plasma, urine and saliva in a couple returning from Martinique, French West Indies.

    Science.gov (United States)

    Fourcade, Camille; Mansuy, Jean-Michel; Dutertre, Marine; Delpech, Marie; Marchou, Bruno; Delobel, Pierre; Izopet, Jacques; Martin-Blondel, Guillaume

    2016-09-01

    While the rapid spread of Zika virus (ZIKV) in South America has been declared a public health emergency few data are available on the kinetics of the virus load and the specific antibodies in individual patients. This report describes the kinetics of ZIKV decay in the body compartments and the kinetics of anti ZIKV IgG and IgM of two people returning from Martinique, French West Indies. ZIKV remained detectable in the plasma for roughly 2 weeks indicating that mosquito control measures should be prolonged accordingly. Remarkably, their urine samples consistently tested positive for even longer. The antibodies responses were different between the two patients but for both the rapid onset of IgM allowed a diagnosis from the end of the first week. PMID:27389909

  6. Viral load of equine herpesviruses 2 and 5 in nasal swabs of actively racing Standardbred trotters: Temporal relationship of shedding to clinical findings and poor performance.

    Science.gov (United States)

    Back, Helena; Ullman, Karin; Treiberg Berndtsson, Louise; Riihimäki, Miia; Penell, Johanna; Ståhl, Karl; Valarcher, Jean-François; Pringle, John

    2015-09-30

    The equine gamma herpesviruses 2 and 5 (EHV-2 and -5) have frequently been observed in the equine population and until recently presumed low to nonpathogenic. However, recent reports linking presence of equine gamma herpesviruses with clinical signs of mild to severe lung disease, suggest that the role of these viruses in respiratory disease and poor performance syndrome is still unclear. Moreover, baseline data regarding the temporal pattern of shedding of EHV-2 and EHV-5 within stables and within individual actively racing horses have been lacking. In a prospective longitudinal study, we followed elite racing Standardbred trotters at monthly intervals for 13 months, to investigate whether the amount of EHV-2 and EHV-5 shedded in nasal secretions varied over time within and between individual horses. Sixty-six elite horses were investigated by analyzing nasal swabs and serum samples, a health check and evaluation of athletic performance monthly during the study period. Nasal swabs were analyzed with two newly developed qPCR assays for EHV-2 and EHV-5, respectively. Of 663 samples, 197 (30%) were positive for EHV-2 and 492 (74%) positive for EHV-5. Furthermore, 176 (27%) of the samples were positive for both EHV-2 and EHV-5 simultaneously. There was considerable variation in the amount and frequency of shedding of EHV-2 and EHV-5 within and between individual horses. Viral load varied seasonally, but neither EHV-2 nor EHV-5 viral peaks were associated with clinical respiratory disease and/or poor performance in racing Standardbred trotters. PMID:26093774

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

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    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.

  8. Relationships between IL-17(+ subsets, Tregs and pDCs that distinguish among SIV infected elite controllers, low, medium and high viral load rhesus macaques.

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    Ladawan Khowawisetsut

    Full Text Available Comprehensive studies of the frequencies and absolute numbers of the various cell lineages that synthesize IL-17 in the blood and corresponding gastrointestinal (GI tissues, their correlation with CD4(+ Tregs, CD8(+ Tregs, total and IFN-α synthesizing plasmacytoid dendritic cells (pDC relative to plasma viral load in SIV infection has been lacking. The unique availability of SIV infected rhesus macaques (RM classified as Elite Controllers (EC, and those with Low, Intermediate and High Viral Loads (HVL provided a unique opportunity to address this issue. Results of these studies showed that EC demonstrated a remarkable ability to reverse changes that are induced acutely by SIV in the various cell lineages. Highlights of the differences between EC and HVL RM within Gastro-intestinal tissues (GIT was the maintenance and/or increases in the levels of IL-17 synthesizing CD4, CD8, and NK cells and pDCs associated with slight decreases in the levels of CD4(+ Tregs and IFN-α synthesizing pDCs in EC as compared with decreases in the levels of IL-17 synthesizing CD4, CD8 and NK cells associated with increases in pDCs and IFN-α synthesizing pDCs in HVL monkeys. A previously underappreciated role for CD8(+ Tregs was also noted with a moderate increase in ECs but further increases of CD8(+ Tregs with increasing VL in viremic monkeys. Positive correlations between plasma VL and decreases in the levels of Th17, Tc17, NK-17, CD4(+ Tregs and increases in the levels of CD8(+ Tregs, total and IFN-α synthesizing pDCs were also noted. This study also identified 2 additional IL-17(+ subsets in GIT as CD3(-/CD8(+/NKG2a(- and CD3(+/CD8(+/NKG2a(+ subsets. Studies also suggest a limited role for IFN-α synthesizing pDCs in chronic immune activation despite persistent up-regulation of ISGs. Finally, elevated persistent innate immune responses appear associated with poor prognosis. These findings provide an initial foundation for markers important to follow for vaccine

  9. Relationships between IL-17(+) subsets, Tregs and pDCs that distinguish among SIV infected elite controllers, low, medium and high viral load rhesus macaques.

    Science.gov (United States)

    Khowawisetsut, Ladawan; Pattanapanyasat, Kovit; Onlamoon, Nattawat; Mayne, Ann E; Little, Dawn M; Villinger, Francois; Ansari, Aftab A

    2013-01-01

    Comprehensive studies of the frequencies and absolute numbers of the various cell lineages that synthesize IL-17 in the blood and corresponding gastrointestinal (GI) tissues, their correlation with CD4(+) Tregs, CD8(+) Tregs, total and IFN-α synthesizing plasmacytoid dendritic cells (pDC) relative to plasma viral load in SIV infection has been lacking. The unique availability of SIV infected rhesus macaques (RM) classified as Elite Controllers (EC), and those with Low, Intermediate and High Viral Loads (HVL) provided a unique opportunity to address this issue. Results of these studies showed that EC demonstrated a remarkable ability to reverse changes that are induced acutely by SIV in the various cell lineages. Highlights of the differences between EC and HVL RM within Gastro-intestinal tissues (GIT) was the maintenance and/or increases in the levels of IL-17 synthesizing CD4, CD8, and NK cells and pDCs associated with slight decreases in the levels of CD4(+) Tregs and IFN-α synthesizing pDCs in EC as compared with decreases in the levels of IL-17 synthesizing CD4, CD8 and NK cells associated with increases in pDCs and IFN-α synthesizing pDCs in HVL monkeys. A previously underappreciated role for CD8(+) Tregs was also noted with a moderate increase in ECs but further increases of CD8(+) Tregs with increasing VL in viremic monkeys. Positive correlations between plasma VL and decreases in the levels of Th17, Tc17, NK-17, CD4(+) Tregs and increases in the levels of CD8(+) Tregs, total and IFN-α synthesizing pDCs were also noted. This study also identified 2 additional IL-17(+) subsets in GIT as CD3(-/)CD8(+)/NKG2a(-) and CD3(+)/CD8(+)/NKG2a(+) subsets. Studies also suggest a limited role for IFN-α synthesizing pDCs in chronic immune activation despite persistent up-regulation of ISGs. Finally, elevated persistent innate immune responses appear associated with poor prognosis. These findings provide an initial foundation for markers important to follow for vaccine

  10. 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.

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

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    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.

  12. DRV concentrations and viral load in CSF in patients on DRV/r 600/100 or 800/100mg once daily plus two NRTI

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    Silvana Di Yacovo

    2014-11-01

    Full Text Available Introduction: Darunavir/r (DRV/r is currently used at a dose of 800/100 mg once daily (OD in a high proportion of patients. Pharmacokinetic data suggest that 600/100 OD may be effective, reducing toxicity and cost. However, drug concentrations in reservoirs such as cerebrospinal fluid (CSF might not be adequate to inhibit viral replication. We aimed to evaluate concentrations of DRV and HIV-1 viral load (VL in CSF patients receiving DRV 600/100 mg OD. Methods: DRV600 is an ongoing randomized open study comparing DRV/r 800/100 mg (DRV800 vs 600/100 mg (DRV600 OD plus TDF/FTC or ABC/3TC in 100 virologically suppressed patients (eudraCT 2011-006272-39. Here we present the results of a CSF sub-study. A lumbar puncture (LP was performed in participating patients after at least six months of inclusion in the study, 20–28 hours after a dose of DRV/r. VL (PCR, LOD 40 copies/mL was determined in CSF and in plasma. DRV concentrations were quantified in CSF by liquid chromatography mass spectrometry (LC/MS/MS and in plasma using high-performance liquid chromatography (HPLC. Results: Sixteen patients were included (eight in each arm. All DRV600 patients and four out of eight DRV800 patients received TDF/FTC, and the other four ABC/3TC. 75% were males, median (range age was 48 (17–71 years, CD4 cell count 532 cells/mL (190–1,394. Median total time on DRV/r was 30 (11–57 months, and since the beginning of the study 8 (6–12 months in DRV800 and 10 (7–12 months in DRV600 patients. LP was performed a median of 26 (24–28 hours after the last DRV/r+TVD or KVX dose. In DRV600 patients the median DRV plasma levels were 1,674 (326–3,742 ng/mL, CSF levels 17.08 (5.79–30.19 ng/mL and DRV CSF:plasma ratio 0.0084 (0.0028–0.0388, while in the DRV800 arm, median DRV plasma levels were 1,707 (958–3,910 ng/mL, CSF levels 13.23 (3.47–32.98 ng/mL and DRV CSF:plasma ratio 0.0104 (0.0018–0.0262. All patients had VL<40 copies/mL in plasma and 14 patients

  13. 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 as...... 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...

  14. 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. PMID:27027882

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

    International Nuclear Information System (INIS)

    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

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

    DEFF Research Database (Denmark)

    Ostrowski, S R; Katzenstein, T L; Pedersen, B K;

    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......-count, CD4+HLA-DR+, CD8+HLA-DR+CD38+, CD4+CD45RA-CD45RO+, CD8+CD45RA-CD45RO+, CD4+CD45RA+CD62L+, CD8+CD45RA+CD62L+ T cells, IgG or IgM. In conclusion, RV was associated with increased blood levels of soluble immune activation markers in HAART-treated HIV-1-infected patients. The finding that RV was...... 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...

  17. 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.

  18. Assessment of the accuracy of dried blood spot (DBS sample in HIV-1 viral load as compared to plasma sample using Abbot assay

    Directory of Open Access Journals (Sweden)

    Prisca Benedicto

    2013-08-01

    Full Text Available Background: HIV has claimed millions of lives with the Sub-Saharan Africa being the most affected. There is a significant increase in access to antiretroviral drugs which also demands frequent monitoring to determine the drug effectiveness and efficacy. Thus there is a great need to evaluate simplified methods to monitor treatment with such antiretroviral drugs. Use of dried blood spots (DBS can be ideal if evaluated in resource limited countries such as Malawi since they are easy to collect, store and convenient. The main objective of this study was to evaluate the accuracy of a dry blood spot sample in the quantification of viral particles in HIV reactive patients using the Abbott m2000rt assay. Methods: 87 participants were recruited from the ART clinic at Queen Elizabeth Central Hospital using convenience sampling method. 29 were on antiretroviral therapy and 58 had not started the therapy. HIV-1 RNA extraction and quantification was performed from DBS and plasma using Abbott m2000sp and m2000rt systems respectively. The results were statistically analyzed by Bland-Altman method using medcalc software version 12.6.1. Results: 66 paired samples with detectable viral loads were analysed. These gave a correlation of 0.98. The mean difference was 0.05 log10 copies/ml with a standard deviation of 0.17 at 95% confidence interval.The Bland-Altman plots showed limits of agreement which ranged from -0.38 to 0.28 log10 copies/ml at 95% confidence interval. Conclusion: Results showed strong agreement between the plasma and DBS samples. A slight and clinically insignificant difference was observed between the two methods. A larger sample size can give support to the study findings. Since samples were less than a week old, it is not known if the results would be different if they were to be stored for a longer period. [Int J Res Med Sci 2013; 1(4.000: 338-342

  19. Renal clearance of melatonin

    OpenAIRE

    Editorial Office

    1996-01-01

    Only two publications exist in which actual values for the renal clearance of intact melatonin in man is described. The melatonin clearance values were, however, obtained either after the oral intake of melatonin, or by applying different techniques for the determination of melatonin in urine and plasma. In this study, renal clearance of melatonin was determined during the hours where melatonin concentrations are relatively constant. Melatonin levels in plasma and urine respectively were e...

  20. The parasite clearance curve

    OpenAIRE

    White NJ

    2011-01-01

    Abstract Parasite clearance rates are important measures of anti-malarial drug efficacy. They are particularly important in the assessment of artemisinin resistance. The slope of the log-linear segment in the middle of the parasite clearance curve has the least inter-individual variance and is the focus of therapeutic assessment. The factors affecting parasite clearance are reviewed. Methods of presentation and the approaches to analysis are discussed.

  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. 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. Viral phylodynamics.

    Directory of Open Access Journals (Sweden)

    Erik M Volz

    Full Text Available Viral phylodynamics is defined as the study of how epidemiological, immunological, and evolutionary processes act and potentially interact to shape viralphylogenies. Since the coining of the term in 2004, research on viral phylodynamics has focused on transmission dynamics in an effort to shed light on how these dynamics impact viral genetic variation. Transmission dynamics can be considered at the level of cells within an infected host, individual hosts within a population, or entire populations of hosts. Many viruses, especially RNA viruses, rapidly accumulate genetic variation because of short generation times and high mutation rates. Patterns of viral genetic variation are therefore heavily influenced by how quickly transmission occurs and by which entities transmit to one another. Patterns of viral genetic variation will also be affected by selection acting on viral phenotypes. Although viruses can differ with respect to many phenotypes, phylodynamic studies have to date tended to focus on a limited number of viral phenotypes. These include virulence phenotypes, phenotypes associated with viral transmissibility, cell or tissue tropism phenotypes, and antigenic phenotypes that can facilitate escape from host immunity. Due to the impact that transmission dynamics and selection can have on viral genetic variation, viral phylogenies can therefore be used to investigate important epidemiological, immunological, and evolutionary processes, such as epidemic spread[2], spatio-temporal dynamics including metapopulation dynamics[3], zoonotic transmission, tissue tropism[4], and antigenic drift[5]. The quantitative investigation of these processes through the consideration of viral phylogenies is the central aim of viral phylodynamics.

  4. A randomized trial of 24 versus 48 weeks of peginterferon α-2a in patients infected with chronic hepatitis C virus genotype 2 or low viral load genotype 1: a multicenter national study in Japan

    OpenAIRE

    Iwasaki, Yoshiaki; Shiratori, Yasushi; Hige, Shuhei; Nishiguchi, Shuhei; Takagi, Hitoshi; Onji, Morikazu; Yoshida, Haruhiko; Izumi, Namiki; Kohgo, Yutaka; Yamamoto, Kyosuke; Sato, Nobuhiro; Shibuya, Akitaka; Saito, Hidetsugu; SATA, MICHIO; Suzuki, Kazuyuki

    2009-01-01

    In a country such as Japan with the average age of patients with chronic hepatitis C treated with antivirals sometimes well above 60 years, the standard combination therapy is not well tolerated. In this randomized, prospective, controlled trial, we investigated the efficacy of 24-week peginterferon α monotherapy for easy-to-treat patients. A total of 132 patients chronically infected with hepatitis C virus (HCV) genotype 2 (n = 115) or low viral load HCV genotype 1 (

  5. B cell depletion in HIV-1 subtype A infected Ugandan adults: relationship to CD4 T cell count, viral load and humoral immune responses.

    Directory of Open Access Journals (Sweden)

    Peter Oballah

    Full Text Available To better understand the nature of B cell dysfunctions in subjects infected with HIV-1 subtype A, a rural cohort of 50 treatment-naïve Ugandan patients chronically infected with HIV-1 subtype A was studied, and the relationship between B cell depletion and HIV disease was assessed. B cell absolute counts were found to be significantly lower in HIV-1+ patients, when compared to community matched negative controls (p<0.0001. HIV-1-infected patients displayed variable functional and binding antibody titers that showed no correlation with viral load or CD4+ T cell count. However, B cell absolute counts were found to correlate inversely with neutralizing antibody (NAb titers against subtype A (p = 0.05 and subtype CRF02_AG (p = 0.02 viruses. A positive correlation was observed between subtype A gp120 binding antibody titers and NAb breadth (p = 0.02 and mean titer against the 10 viruses (p = 0.0002. In addition, HIV-1 subtype A sera showed preferential neutralization of the 5 subtype A or CRF02_AG pseudoviruses, as compared with 5 pseudoviruses from subtypes B, C or D (p<0.001. These data demonstrate that in patients with chronic HIV-1 subtype A infection, significant B cell depletion can be observed, the degree of which does not appear to be associated with a decrease in functional antibodies. These findings also highlight the potential importance of subtype in the specificity of cross-clade neutralization in HIV-1 infection.

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

    Directory of Open Access Journals (Sweden)

    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.

  7. 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)

    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. PMID:27383834

  8. Blocking of α4β7 Gut-Homing Integrin during Acute Infection Leads to Decreased Plasma and Gastrointestinal Tissue Viral Loads in Simian Immunodeficiency Virus-Infected Rhesus Macaques

    OpenAIRE

    Aftab A. Ansari; Reimann, Keith A.; Mayne, Ann E.; Takahashi, Yoshiaki; Stephenson, Susan T.; Wang, Rijian; Wang, Xinyue; Li, JiChu; Price, Andrew A.; Little, Dawn M.; Zaidi, Mohammad; Lyles, Robert; Villinger, Francois

    2010-01-01

    Intravenous administration of a novel recombinant rhesus mAb against the α4β7 gut-homing integrin (mAb) into rhesus macaques just prior to and during acute SIV infection resulted in significant decrease in plasma and gastrointestinal (GI) tissue viral load and a marked reduction in GI tissue proviral DNA load as compared with control SIV-infected rhesus macaques. This mAb administration was associated with increases in peripheral blood naive and central memory CD4+ T cells and maintenance of ...

  9. Calculating Clearances for Manipulators

    Science.gov (United States)

    Copeland, E. L.; Peticolas, J. D.; Ray, L. D.

    1983-01-01

    Set of algorithms rapidly calculates minimum safe clearances for remote manipulators. Such calculations are used in design of trajectories for manipulators to ensure they do not accidentally strike surrounding objects. Structural parts are considered as cylindrical shells having circular plane areas for ends. Clearance calculation method offers special benefits in industrial robotics, particularly in automated machining.

  10. 14 CFR 29.411 - Ground clearance: tail rotor guard.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Ground clearance: tail rotor guard. 29.411... System Loads § 29.411 Ground clearance: tail rotor guard. (a) It must be impossible for the tail rotor to contact the landing surface during a normal landing. (b) If a tail rotor guard is required to...

  11. 14 CFR 27.411 - Ground clearance: tail rotor guard.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Ground clearance: tail rotor guard. 27.411... System Loads § 27.411 Ground clearance: tail rotor guard. (a) It must be impossible for the tail rotor to contact the landing surface during a normal landing. (b) If a tail rotor guard is required to...

  12. 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

  13. 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.

  14. 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

    OpenAIRE

    Theys, Kristof; Deforche, Koen; Vercauteren, Jurgen; Libin, Pieter; van de Vijver, David A M C; Albert, Jan; Åsjø, Birgitta; Balotta, Claudia; Bruckova, Marie; Camacho, Ricardo J; Clotet, Bonaventura; Coughlan, Suzie; Grossman, Zehava; Hamouda, Osamah; Horban, Andrzei

    2012-01-01

    Background: 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 mutations, often already polymorphic in wild-type viruses, do not tend to revert after transmission. While compensatory mutations increase fitness during treatment, their presence may also modulate viral fitness and ...

  15. 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.

    OpenAIRE

    Theys, Kristof; Deforche, Koen; Vercauteren, Jurgen; Libin, Pieter; van de Vijver, David Amc; Albert, Jan; Asjo, Birgitta; Balotta, Claudia; Bruckova, Marie; Camacho, Ricardo J; Clotet, Bonaventura; Coughlan, Suzie; Grossman, Zehava; Hamouda, Osamah; Horban, Andrzei

    2012-01-01

    BACKGROUND: 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 mutations, often already polymorphic in wild-type viruses, do not tend to revert after transmission. While compensatory mutations increase fitness during treatment, their presence may also modulate viral fitness and ...

  16. VIRAL MARKETING

    OpenAIRE

    Howeidi, Mohammad; Nguyen, David

    2016-01-01

    Advancements in communication technology has given rise to the new phenomenon of viral marketing. Virality has become the new buzzword organizations desire and marketers adopt. The fundamental goal remains the same that is to increase awareness of a product or service. With this in mind, the objective of this study is to explore viral marketing through a content and receptiom analysis, so that marketers can gain a better understanding of how and which elements have driven two s...

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

    Directory of Open Access Journals (Sweden)

    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

  18. Operationalizing treatment as prevention in Los Angeles County: antiretroviral therapy use and factors associated with unsuppressed viral load in the Ryan White system of care.

    Science.gov (United States)

    Sayles, Jennifer N; Rurangirwa, Jacqueline; Kim, Min; Kinsler, Janni; Oruga, Rangell; Janson, Mike

    2012-08-01

    Despite extensive prevention efforts, an estimated 21% of individuals with HIV/AIDS in the United States are unaware of their status, placing them at greater risk for spreading the virus to others. HIV treatment as prevention (TasP) is rapidly becoming an important public health strategy to reduce HIV transmission at the population level. Data for this study were collected on a sample of 11,397 HIV-positive individuals in the Ryan White system, a publicly funded system of care for HIV-positive individuals in Los Angeles County who are uninsured, in 2009 to examine two components of TasP: baseline rates and factors associated with antiretroviral therapy (ART) use and viral load (VL) suppression in a publicly funded system of care. ART coverage among our sample was 90%. In multivariate analyses, those with a higher odds of having unsuppressed VL included: females compared to males (adjusted odds ratio [AOR]=1.25; 95% confidence interval [CI]=1.06, 1.47); African Americans compared to whites (AOR=1.42; 95% CI=1.24, 1.62); men who have sex with men compared to heterosexuals (AOR=1.15; 95% CI=1.00, 1.32); recent substance abusers compared to nonsubstance abusers (AOR=1.35; 95% CI=1.17, 1.55); those recently incarcerated or ever incarcerated compared to those never incarcerated (AOR=1.37; 95% CI=1.15, 1.63; and AOR=1.28; 95% CI=1.09, 1.50); and those retained in care compared to those not retained in care (AOR=1.98; 95% CI=1.76, 2.22). Understanding the key sociodemographic, geographic and behavioral factors associated with ART use as well as HIV VL suppression will be useful for informing the development and deployment of targeted programming and policies that may further enhance the implementation of the TasP approach in communities across the United States. PMID:22775237

  19. 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

  20. Incidence and clearance of anal high-risk human papillomavirus in HIV-positive men who have sex with men: estimates and risk factors

    Science.gov (United States)

    Geskus, Ronald B.; González, Cristina; Torres, Montserrat; Del Romero, Jorge; Viciana, Pompeyo; Masiá, Mar; Blanco, José R.; Iribarren, Mauricio; De Sanjosé, Silvia; Hernández-Novoa, Beatriz; Ortiz, Marta; Del Amo, Julia

    2016-01-01

    Background: To estimate incidence and clearance of high-risk human papillomavirus (HR-HPV), and their risk factors, in men who have sex with men (MSM) recently infected by HIV in Spain; 2007–2013. Methods: Multicenter cohort. HR-HPV infection was determined and genotyped with linear array. Two-state Markov models and Poisson regression were used. Results: We analysed 1570 HR-HPV measurements of 612 MSM over 13 608 person-months (p-m) of follow-up. Median (mean) number of measurements was 2 (2.6), median time interval between measurements was 1.1 years (interquartile range: 0.89–1.4). Incidence ranged from 9.0 [95% confidence interval (CI) 6.8–11.8] per 1000 p-m for HPV59 to 15.9 (11.7–21.8) per 1000 p-m for HPV51. HPV16 and HPV18 had slightly above average incidence: 11.9/1000 p-m and 12.8/1000 p-m. HPV16 showed the lowest clearance for both ‘prevalent positive’ (15.7/1000 p-m; 95% CI 12.0–20.5) and ‘incident positive’ infections (22.1/1000 p-m; 95% CI 11.8–41.1). More sexual partners increased HR-HPV incidence, although it was not statistically significant. Age had a strong effect on clearance (P-value < 0.001) due to the elevated rate in MSM under age 25; the effect of HIV-RNA viral load was more gradual, with clearance rate decreasing at higher HIV-RNA viral load (P-value 0.008). Conclusion: No large variation in incidence by HR-HPV type was seen. The most common incident types were HPV51, HPV52, HPV31, HPV18 and HPV16. No major variation in clearance by type was observed, with the exception of HPV16 which had the highest persistence and potentially, the strongest oncogenic capacity. Those aged below 25 or with low HIV-RNA- viral load had the highest clearance. PMID:26355673

  1. Renal Clearance of Nanoparticles

    OpenAIRE

    Choi, Hak Soo; Liu, Wenhao; Misra, Preeti; Tanaka, Eiichi; Zimmer, John P.; Ipe, Binil Itty; Bawendi, Moungi G.; Frangioni, John V.

    2007-01-01

    The field of nanotechnology holds great promise for the diagnosis and treatment of human disease. However, the size and charge of most nanoparticles preclude their efficient clearance from the body as intact nanoparticles. Without such clearance or their biodegradation into biologically benign components, toxicity is potentially amplified and radiological imaging is hindered. Using quantum dots (QDs) as a model system, we have precisely defined the requirements for renal filtration and urinar...

  2. Optimisation-based clearance

    OpenAIRE

    Varga, Andras

    2002-01-01

    The basic feature of the optimisation-based clearance approach is to reformulate the clearance problems as equivalent minimum distance problems for which ”anti”-optimisation is performed to determine the worst-case parameter combination/ flight condition leading to worst performance. The basic requirements for the applicability of the optimisation-based approach are the availability of suitable parametric models describing the overall nonlinear dynamics of the augmented aircraft and of accomp...

  3. Correlation between cytokine serum levels, number of CD4+ T cells/mm³ and viral load in HIV-1 infected individuals with or without antiretroviral therapy

    Directory of Open Access Journals (Sweden)

    D. A. Meira

    2004-01-01

    Full Text Available Seventy-nine HIV-1 infected patients were studied in three groups: Group G1 - 11 patients with no antiretroviral therapy; G2 - 40 patients undergoing antiretroviral therapy, 33 with only two nucleoside reverse transcriptase inhibitors (NRTI, and seven with two NRTI and one protease inhibitor (PI, all with viral load (VL equal or higher than 80 copies of plasma RNA/ml; Group G3 - 28 patients, 23 on highly active antiretroviral therapy (HAART, 18 with two NRTI and one PI, and five with two NRTI and one non-nucleoside reverse transcriptase inhibitor (NNRTI, the remaining five with combination of two NRTI. All G3 patients had undetectable viral load for at least the past six months. The control group (Gc included 20 normal blood donors without clinical complaints or signs of disease and negative for anti-HIV-1/2 antibodies. Serum cytokine levels pg/ml (TNF-alpha, INF-gamma, IL-2, IL-4, and IL-10 were determined in all patients including controls. CD4+ T and CD8+ T lymphocyte counts were made in the 79 patients by flow cytometry; VL determination was by NASBA technology. Analysis of results showed that the number of CD4+ T and CD8+ T lymphocytes were higher in G2 than G1, while VL was 0.5 log lower. G3 patients had similar lymphocyte values to G2, however they were chosen for G3 because their VL was undetectable, different by 4.0 log to G2. These results show the effect of antiretroviral treatment in G2 and G3 patients with better performance in the latter. Statistical difference was seen between the three groups and controls for serum cytokine behavior: TNF-alpha [H=48.323; pGc]; INF-gamma[H=28.992; pGc]; IL-4[H=48.323; pGc]; IL-10[H=47.256; pGc. There was no statistical difference in IL-2 values between all groups (H=6.071; p>0.10; G1=G2=G3=Gc. In absolute values however, G3 showed slightly lower TNF-alpha, IL-4, and IL-10, and higher INF-gamma and IL-2, to G1 and G2. This suggests a better performance in G3 patients, especially in IL-2 behavior

  4. A whole recombinant yeast-based therapeutic vaccine elicits HBV X, S and Core specific T cells in mice and activates human T cells recognizing epitopes linked to viral clearance.

    Directory of Open Access Journals (Sweden)

    Thomas H King

    Full Text Available Chronic hepatitis B infection (CHB is characterized by sub-optimal T cell responses to viral antigens. A therapeutic vaccine capable of restoring these immune responses could potentially improve HBsAg seroconversion rates in the setting of direct acting antiviral therapies. A yeast-based immunotherapy (Tarmogen platform was used to make a vaccine candidate expressing hepatitis B virus (HBV X, surface (S, and Core antigens (X-S-Core. Murine and human immunogenicity models were used to evaluate the type and magnitude of HBV-Ag specific T cell responses elicited by the vaccine. C57BL/6J, BALB/c, and HLA-A*0201 transgenic mice immunized with yeast expressing X-S-Core showed T cell responses to X, S and Core when evaluated by lymphocyte proliferation assay, ELISpot, intracellular cytokine staining (ICS, or tumor challenge assays. Both CD4+ and CD8+ T cell responses were observed. Human T cells transduced with HBc18-27 and HBs183-91 specific T cell receptors (TCRs produced interferon gamma (IFNγ following incubation with X-S-Core-pulsed dendritic cells (DCs. Furthermore, stimulation of peripheral blood mononuclear cells (PBMCs isolated from CHB patients or from HBV vaccine recipients with autologous DCs pulsed with X-S-Core or a related product (S-Core resulted in pronounced expansions of HBV Ag-specific T cells possessing a cytolytic phenotype. These data indicate that X-S-Core-expressing yeast elicit functional adaptive immune responses and supports the ongoing evaluation of this therapeutic vaccine in patients with CHB to enhance the induction of HBV-specific T cell responses.

  5. 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.

  6. 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.

  7. Comparison of the health-related quality of life, CD4 count and viral load of AIDS patients and people with HIV who have been on treatment for 12 months in rural South Africa

    OpenAIRE

    Igumbor, Jude; Stewart, Aimee; Holzemer, William

    2013-01-01

    This study compared the level of CD4 count, viral load and health-related quality of life (HRQOL) between treatment-naïve AIDS patients and a cohort of people living with HIV who have been on treatment for 12 months. This study is based on a secondary data analysis of the records of 642 people with HIV consisting of 311 treatment-naïve AIDS patients and 331 people with HIV who have been on treatment for 12 months. The study findings are mostly presented in tables and analysed using the t-test...

  8. Generic Clearance Values

    International Nuclear Information System (INIS)

    This paper analyzes the Generic Clearance Values established for natural and artificial radionuclides with the objective of evaluating their degree of conservatism in views of adopting them into the regulatory body. Generic clearance values for natural radionuclides have been chosen by experts judgments as the optimum boundary between, on the one hand, the ubiquitous unmodified soil concentrations and, on the other hand, activity concentrations in ores, mineral sands, industrial residues and wastes. For artificial radionuclides the clearance levels have been derived from the scenarios postulated in the document Safety Reports Series 44 of the IAEA considering quantitative exemption criteria. A set of 8 scenarios were postulated covering external, ingestion and inhalation exposure pathways. For each radionuclide, the generic clearance level was derived as the more restrictive value obtained from the scenarios, that is the lowest ratio between the applicable individual dose and the dose per unit activity concentration (Bq/g). The individual dose was calculated by a formula depending on each scenario and pathway, with different parameters, such as exposure time, dosimetric factors, dilution factor, density of the material, geometric factors, etc. It was concluded that the basis and parameters used for the derivation of the generic clearance levels are quite conservative and therefore its the adoption in Argentina has been recommended. It is expected that their implementation will contribute to optimize the regulatory management system. (authors)

  9. Generic clearance values

    International Nuclear Information System (INIS)

    This paper analyzes the Generic Clearance Values established for natural and artificial radionuclides with the objective of evaluating their degree of conservatism in views of adopting them into the regulatory body. Generic clearance values for natural radionuclides have been chosen by experts judgments as the optimum boundary between, on one hand, the ubiquitous unmodified soil concentrations and, on the other hand, activity concentrations in ores, mineral sands, industrial residues and wastes. For artificial radionuclides the clearance levels have been derived from the scenarios postulated in the document 'Safety Reports Series Nr 44' of the IAEA considering quantitative exemption criteria. A set of 8 scenarios were postulated covering external, ingestion and inhalation exposure pathways. For each radionuclide, the generic clearance level was derived as the more restrictive value obtained from the scenarios, that is the lowest ratio between the applicable individual dose and the dose per unit activity concentration (Bq/g). The individual dose was calculated by a formula depending on each scenario and pathway, with different parameters, such as exposure time, dosimetric factors, dilution factor, density of the material, geometric factors, etc. It was concluded that the basis and parameters used for the derivation of the generic clearance levels are quite conservative and therefore its the adoption in Argentina has been recommended. It is expected that their implementation will contribute to optimize the regulatory management system. (author)

  10. Study on clearance system

    International Nuclear Information System (INIS)

    The clearance system is a legal system to release 'the radioactive waste not requiring treatment as radioactive waste' from the regulatory control. JNES supports NISA on approval and confirmation of clearance measurement and judgment developed by the operator. The objective of this study is to establish technical base of the validation method of the clearance measurement for various objects. In reactor facilities, the bulk measurement technique or the statistical sampling measurement technique may be applied to large scale objects or concrete walls. In this study, the criteria of those techniques were examined. In uranium processing facilities, it is important to confirm surface state of the object in case of detecting alpha rays. The result of the examination about the influence of the surface rust in the uranium clearance measurement by the alpha ray measurement showed that the pollution was distributed in rust layer uniformly. This result will be reflected to the revision of the Ministerial Ordinance on Clearance in 2011FY. To develop a manual for unexpected incidents, the response procedure for an unexpected incident was prepared, including a response system. (author)

  11. Study on clearance system

    International Nuclear Information System (INIS)

    The clearance system is a legal word to define as 'the waste not requiring treatment as radioactive waste' on the regulatory control. JNES supports NISA on the approval and the confirmation of clearance measurement by the operator. The objective of this study is to establish technical base of the validation method of the clearance measurement for various objects. In reactor facilities, the statistical sampling measurement technique may be applied to large scale objects. In this study, the criteria of the techniques were examined, and the strategy for setting of radioactivity concentration evaluation level was prepared. In uranium processing facilities, simulation sources to apply to a validity confirmation examination of the measuring equipment were made, and these applicability and problem were studied. The method of the validity evaluation of the performance confirmation of the measuring equipment was devised by measurement experiment using this source. The manual for unexpected incidents which maintained in FY2011 was reviced by reflection of the experience of the radioactivity concentration measurement of disaster waste contaminated by the accident of Fukushima Dai-ichi NPS. JNES also supports NISA technically for the issue on influence of fall out from Fukushima Dai-ichi NPS on clearance system and NR system. In addition, the latest situation of a clearance system operated in Europe was studied. (author)

  12. 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

  13. 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.

  14. 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; 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; 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.B. 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

  15. 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...

  16. Viral marketing

    OpenAIRE

    Strømberg, Sebastian

    2013-01-01

    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...

  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. Pharyngitis - viral

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/001392.htm Pharyngitis - viral To use the sharing features on this page, please enable JavaScript. Pharyngitis , or sore throat, is swelling, discomfort, pain, or ...

  19. Viral pneumonia

    Science.gov (United States)

    More serious infections can result in respiratory failure, liver failure, and heart failure. Sometimes, bacterial infections occur during or just after viral pneumonia, which may lead to more serious forms ...

  20. Viral Hepatitis

    Science.gov (United States)

    ... Hepatitis viruses B and C can cause both acute and chronic infections. Chronic hepatitis B and C are serious health problems. They can lead to: Cirrhosis (suh-ROH-suhs) Liver failure Liver cancer Return to top How is viral ...

  1. 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.

  2. Viral Marketing

    OpenAIRE

    Sorina Raula Gîrboveanu; Silvia Puiu

    2008-01-01

    With consumers showing increasing resistance to traditional forms of advertising such as TV or newspaper ads, marketers have turned to alternate strategies, including viral marketing. Viral marketing exploits existing social networks by encouraging customers to share product information with their friends.In our study we are able to directly observe the effectiveness of person to person word of mouth advertising for hundreds of thousands of products for the first time

  3. 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

    2015-12-01

    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. PMID:26297125

  4. Study on clearance system

    International Nuclear Information System (INIS)

    The clearance system is a legal system to release 'the radioactive waste not requiring treatment as radioactive waste' from the regulatory control. JNES supports Nuclear Regulatory Agency on approval and confirmation of clearance measurement and judgment developed by the operator. The objective of this study is to establish technical base of the validation method of the clearance measurement for various objects. In uranium processing facilities, simulation sources emitting alpha-rays is used in a validity confirmation examination of the measuring equipment. In this study, these sources were examined by measuring alpha and beta spectra to evaluate the applicability and problem of these sources. In addition, the measuring method detecting gamma-rays was examined. This method can be applied to complicated objects. As a part to develop a manual for unexpected incidents in clearance system, a quick method for measurement of Strontium 90 was examined. In addition, the measuring methods for the judgment of the influence of fallout and for NR (Non-Radioactive) confirmation were examined. (author)

  5. 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; Larsen, Mette Vang; Schønning, Kristian; Benfield, Thomas

    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....

  6. Viral arthritis.

    Science.gov (United States)

    Marks, Michael; Marks, Jonathan L

    2016-04-01

    Acute-onset arthritis is a common clinical problem facing both the general clinician and the rheumatologist. A viral aetiology is though to be responsible for approximately 1% of all cases of acute arthritis with a wide range of causal agents recognised. The epidemiology of acute viral arthritis continues to evolve, with some aetiologies, such as rubella, becoming less common due to vaccination, while some vector-borne viruses have become more widespread. A travel history therefore forms an important part of the assessment of patients presenting with an acute arthritis. Worldwide, parvovirus B19, hepatitis B and C, HIV and the alphaviruses are among the most important causes of virally mediated arthritis. Targeted serological testing may be of value in establishing a diagnosis, and clinicians must also be aware that low-titre autoantibodies, such as rheumatoid factor and antinuclear antibody, can occur in the context of acute viral arthritis. A careful consideration of epidemiological, clinical and serological features is therefore required to guide clinicians in making diagnostic and treatment decisions. While most virally mediated arthritides are self-limiting some warrant the initiation of specific antiviral therapy. PMID:27037381

  7. Mucociliary clearance in chronic sinusitis

    OpenAIRE

    Birdi, Surinder Mohan; Singh, Sunder; Singh, Ajit

    1998-01-01

    Mucociliary clearance is an important defence mechanism of upper and lower respiratory tracts. Any disturbance in the mechanism leads to stagnation of secretions and secondary infection with prolonged mucociliary clearance time. The present study was undertaken to establish normal mucociliary clearance time in our region and to evaluate its diagnostic and prognostic potential in chronic sinusitis of variable duration with and without obstructive diseases.

  8. Viral Marketing

    OpenAIRE

    Jelínková, Petra

    2012-01-01

    Diploma thesis is focused on Viral marketing, as a part of internet marketing communication i.e. iPromotion. It’s presented as a „niche” in the way of reaching the target group (audience) that rejects traditional forms of promotion. There’s an explanation of differences between various types of viral marketing as well as proposed possibilities of it’s applying into a practice including the rules of campaign execution. The primary data sources, necessary for the solution of investigated issue...

  9. Veterinary field test as screening tool for mastitis and HIV-1 viral load in breastmilk from HIV-infected Zambian women.

    Science.gov (United States)

    Dorosko, Stephanie M; Thea, Donald M; Saperstein, George; Russell, Robert M; Paape, Max J; Hinckley, Lynn S; Decker, William D; Semrau, Katherine; Sinkala, Moses; Kasonde, Prisca; Kankasa, Chipepo; Aldrovandi, Grace M; Hamer, Davidson H

    2007-09-01

    Clinical and subclinical mastitis increase the risk of mother-to-child transmission (MTCT) of HIV-1 through breastfeeding. We hypothesized that a field test for mastitis used for bovine milk, the California Mastitis Test, would detect high cell counts in milk of HIV-infected women. We also investigated whether total milk cell count would positively correlate with viral HIV-1 RNA in the milk of 128 HIV-positive Zambian women. Mean cell counts in each California Mastitis Test scoring category were significantly different (p tested for HIV-1 RNA, viral RNA levels did not significantly correlate with total cell count (r = 0.166, p = .244). The CMT may serve as a screening tool for mastitis in breastmilk, but total cell count does not correlate with HIV-1 RNA levels. Since both cell-free and cell-associated virus are associated with increased risk of MTCT, investigation of the relationship between total milk cell count and HIV-1 proviral DNA is warranted before a conclusive determination is made regarding use of the CMT as a clinical screening tool to detect cases at high risk for breastmilk transmission. PMID:17903106

  10. Aerosol Delivery of a Candidate Universal Influenza Vaccine Reduces Viral Load in Pigs Challenged with Pandemic H1N1 Virus.

    Science.gov (United States)

    Morgan, Sophie B; Hemmink, Johanneke D; Porter, Emily; Harley, Ross; Shelton, Holly; Aramouni, Mario; Everett, Helen E; Brookes, Sharon M; Bailey, Michael; Townsend, Alain M; Charleston, Bryan; Tchilian, Elma

    2016-06-15

    Influenza A viruses are a major health threat to livestock and humans, causing considerable mortality, morbidity, and economic loss. Current inactivated influenza vaccines are strain specific and new vaccines need to be produced at frequent intervals to combat newly arising influenza virus strains, so that a universal vaccine is highly desirable. We show that pandemic H1N1 influenza virus in which the hemagglutinin signal sequence has been suppressed (S-FLU), when administered to pigs by aerosol can induce CD4 and CD8 T cell immune responses in blood, bronchoalveolar lavage (BAL), and tracheobronchial lymph nodes. Neutralizing Ab was not produced. Detection of a BAL response correlated with a reduction in viral titer in nasal swabs and lungs, following challenge with H1N1 pandemic virus. Intratracheal immunization with a higher dose of a heterologous H5N1 S-FLU vaccine induced weaker BAL and stronger tracheobronchial lymph node responses and a lesser reduction in viral titer. We conclude that local cellular immune responses are important for protection against influenza A virus infection, that these can be most efficiently induced by aerosol immunization targeting the lower respiratory tract, and that S-FLU is a promising universal influenza vaccine candidate. PMID:27183611

  11. Phagocytic Clearance in Neurodegeneration

    OpenAIRE

    Sokolowski, Jennifer D.; Mandell, James W.

    2011-01-01

    The cellular and molecular mechanisms of phagocytic clearance of apoptotic cells and debris have been intensely studied in invertebrate model organisms and in the mammalian immune system. This evolutionarily conserved process serves multiple purposes. Uncleared debris from dying cells or aggregated proteins can be toxic and may trigger exaggerated inflammatory responses. Even though apoptotic cell death and debris accumulation are key features of neurodegenerative diseases, relatively little ...

  12. Modelling mucociliary clearance

    OpenAIRE

    Smith, D.J.; Gaffney, E.A.; Blake, J R

    2008-01-01

    Mathematical modelling of the fluid mechanics of mucociliary clearance (MCC) is reviewed and future challenges for researchers are discussed. The morphology of the bronchial and tracheal airway surface liquid (ASL) and ciliated epithelium are briefly introduced. The cilia beat cycle, beat frequency and metachronal coordination are described, along with the rheology of the mucous layer. Theoretical modelling of MCC from the late 1960s onwards is reviewed, and distinctions between ‘phenomenolog...

  13. VIRAL GASTROENTERITIS

    Science.gov (United States)

    Two virus types have been clearly shown to have epidemiologic importance in viral gastroenteritis, i.e., rotavirus and Norwalk virus. Four other virus types have been associated with gastroenteritis but their epidemiologic importance is not yet known, i.e., enteric adenovirus, ca...

  14. Distribution of hepatitis B virus genotypes and viral load levels in Brazilian chronically infected patients in São Paulo city Distribuição dos genótipos do vírus da hepatite B e níveis de carga viral em pacientes brasileiros cronicamente infectados na cidade de São Paulo

    Directory of Open Access Journals (Sweden)

    Rosana Alcalde

    2009-10-01

    Full Text Available The objective of the present study was to evaluate the serum viral load in chronically infected Hepatitis B virus (HBV patients and to investigate the distribution of HBV genotypes in São Paulo city. Quantitative HBV-DNA assays and HBV genotyping have gained importance for predicting HBV disease progression, have been employed for assessing infectivity, for treatment monitoring and for detecting the emergence of drug resistance. Twenty-nine Brazilian patients with suspected chronic hepatitis B were studied, using real time PCR for viral load determination and direct DNA sequencing for the genotyping. The serology revealed chronic HBV infection in 22 samples. The HBV-DNA was positive in 68% samples (15/22. The phylogenetic analysis disclosed that eleven patients were infected with HBV genotype A, two with genotype F and two with genotype D. Thus, the genotype A was the most prevalent in our study.O objetivo do presente estudo foi avaliar a carga viral no soro de pacientes cronicamente infectados pelo vírus da Hepatite B (HBV e investigar a distribuição de genótipos HBV na cidade de São Paulo. PCR quantitativo do HBV e genotipagem ganharam importância para a previsão de progressão da doença, empregada para avaliar a infectividade, para tratamento e acompanhamento e para detectar o aparecimento de resistência aos anti-retrovirais. Vinte e nove pacientes brasileiros com suspeita de hepatite B crônica foram estudados, utilizando PCR em tempo real para a determinação da carga viral e seqüenciamento direto para determinação do genótipo. A sorologia revelou que 22 estavam, de fato, cronicamente infectados pelo HBV. O HBV-DNA foi positivo em 68% das amostras (15/22. Em sete casos, HBV-DNA foi indetectável por PCR quantitativo. A análise filogenética mostra que onze pacientes foram infectados com hepatite B genótipo A, dois com genótipo F e dois com genótipo D. Desta forma, o genótipo A foi o mais prevalente em nosso estudo.

  15. Effect of cardiovascular interventional treatment on clearance of biological load on contaminated catheter%心血管介入诊疗中污染导管的生物负载清除效果研究

    Institute of Scientific and Technical Information of China (English)

    张永栋; 柳茵; 刘维军; 李琳

    2012-01-01

    目的 研究通过规范的清洗和灭菌方法对污染的心脏电生理导管微生物负载清除效果.方法 将心脏电生理导管使用HBV血液进行污染,分为5组,每组40根导管,A组采用多酶清洗,B组采用加去污剂清洗,C组采用多酶加去污剂清洗,D组采用去污剂和多酶清洗后环氧乙烷低温灭菌,E组术进行任何处理,作为阳性对照组;再将每段分为各5 mm的两节,其中一节采用PCR检测各组HIV核酸阳性数;另一节与人肝细胞共同培养收集培养上清液检测HBsAg和HBeAg;观察人肝细胞的存活情况.结果 A组检出HBV-DNA阳性39根,阳性率为97.5%,人肝细胞大量死亡;B组检出HBV-DNA阳性37 根,阳性率92.5%,人肝细胞生长状况不良;C组检出HBV-DNA阳性37根,阳性率92.5%,人肝细胞大量死亡;D组未检出 HBV-DNA,入肝细胞生长状况良好;E组检出HBV-DNA阳性40根,阳性率100.0%,人肝细胞大量死亡.结论 清洗(去污剂+酶液)+环氧乙烷低温灭菌法可有效清除心脏电生理导管的HBV污染,从消除导管生物负载的角度为今后探索导管复用、为取得相关政策的支持提供了科学依据.%OBJECTIVE To study the effect of the standardized cleaning and sterilization methods on the clearance of the bacterial load on the contaminated cardiac eiectrophysiology catheter. METHODS The cardiac electrophysiology catheters with HBV blood pollution were divided into five groups with 40 in each, the group A was treated with multiple enzymes, the group B with detergents for cleaning, the group C with detergent plus multi-enzyme, the group D with ethylene oxide for low temperature sterilization after using multiple enzymes and detergent, the group E without any trealmeni as the positive control group; then each section were divided into two 5 mm-segments, one was detected the positive HBV nucleic acid with PCR; the other was measured for the HBsAg and HbeAg with the combined culture with human liver

  16. Differential effects of viral silencing suppressors on siRNA and miRNA loading support the existence of two distinct cellular pools of ARGONAUTE1

    OpenAIRE

    Schott, Gregory; Mari-Ordonez, Arturo; Himber, Christophe; Alioua, Abdelmalek; Voinnet, Olivier; Dunoyer, Patrice

    2012-01-01

    Plant viruses encode suppressors (VSRs) that target the host antiviral RNA silencing pathway. Here, VSRs are shown to differentially impair siRNA and miRNA binding to Argonaute1, AGO1, revealing distinct AGO1 pools that are preferentially loaded with either siRNAs or miRNAs.

  17. Correlation between viral load, plasma levels of CD4 - CD8 T lymphocytes and AIDS-related oral diseases: a multicentre study on 30 HIV+ children in the HAART era.

    Science.gov (United States)

    Nesti, M; Carli, E; Giaquinto, C; Rampon, O; Nastasio, S; Giuca, M R

    2012-01-01

    This experimental retrospective multicenter study carried out on 30 seropositive children treated with Highly Active Antiretroviral Therapy (HAART), between the ages of 18 months and 14 years, in the clinical categories Centers for Disease Control (CDC) classification 1993 A (mildly symptomatic), B (moderately symptomatic) and C (severely symptomatic) aims to: 1) clinically and immunologically demonstrate the therapeutic benefits of HAART; 2) monitor the frequency of AIDS-related oral diseases in seropositive children with HAART therapy; 3) monitor the plasma levels of total CD4, CD4 percent, CD8 percent, CD4-CD8 lymphocytes and viral load from 1997 to 30 April, 2011. The statistic methods used are the analysis of covariance and the Bonferroni Test. More than 100 AIDS-related oral diseases were found in the study samples, the most frequent being: oral candidiasis, oropharyngeal candidiasis, HSV-1 herpetic esophagyitis, herpetic gingivolstomatitis (RHOG), recurrent aphthous stomatitis (RAS), parotid swelling, oral hairy leukoplakia (OHL), Herpes simplex 1 (HSV-1), linear gingival erythema (LGE), necrotizing gingivitis (NUG), facial lipodistrophy, facial-cervical lymphadenopathy (FCL), xerostomia, dysgeusia, hyposmia, oral mucosa hyperpigmentation (OMP). The Bonferroni test showed a significant difference between the mean plasma values (mpVTL) of total CD4, CD4 percentage, CD4-CD8 T lymphocytes and Viral Load (VL) of the various oral diseases found in the study samples. The therapeutic benefits of HAART are: immune reconstitution; reduction of the HIV/AIDS-related stomatology diseases; prevention and cure of the AIDS correlated neoplasias; reduction in maternal-fetal transmission of the HIV virus. The negative effects of HAART in relation to odontostomatolgy are: increase in oral lesions from HPV; xerostomia; dysgeusia/ageusia, hyposmia, perioral paresthesia; hyperpigmentation of oral mucosa; facial lipodystrophy, recurrent aphthous stomatitis (RAS). No case of

  18. 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

  19. 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.

  20. Family study of antipyrine clearance.

    OpenAIRE

    Blain, P G; Mucklow, J C; Wood, P; Roberts, D F; Rawlins, M D

    1982-01-01

    Antipyrine clearance was measured in 208 healthy volunteers from 78 families. After the values had been corrected for weight and sex, antipyrine clearance was observed to be significantly correlated between siblings (r = 0.590) and between spouses (r = 0.320), but not between parents and their offspring. After the clearance values had been corrected for tobacco and oral contraceptive use, there was still no significant correlation between parents and offspring. These results are incompatible ...

  1. 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.

  2. Virales Marketing

    OpenAIRE

    Nufer, Gerd; Schattner, Pascal

    2010-01-01

    Konsumenten werden heutzutage von Werbung regelrecht erschlagen. Jeden Tag prasseln tausende von Werbebotschaften auf die Menschen ein. Diese bilden einen natürlichen Widerstand dagegen und nehmen so wenig wie möglich auf, um sich auf wichtige Informationen konzentrieren zu können. Die klassische Werbung steckt in einer großen Krise und Unternehmen müssen einen neuen Weg finden, ihren Kunden unbemerkt Werbung zukommen zu lassen. Genau hier setzt Virales Marketing an. Denn in den meisten Fälle...

  3. Development and optimization of a sensitive TaqMan® real-time PCR with synthetic homologous extrinsic control for quantitation of Human cytomegalovirus viral load.

    Science.gov (United States)

    Slavov, Svetoslav Nanev; Otaguiri, Katia Kaori; de Figueiredo, Glauciane Garcia; Yamamoto, Aparecida Yulie; Mussi-Pinhata, Marisa Marcia; Kashima, Simone; Covas, Dimas Tadeu

    2016-09-01

    Human cytomegalovirus (Human herpesvirus 5, HCMV) causes frequent asymptomatic infections in the general population. However, in immunosuppressed patients or congenitally infected infants, HCMV is related to high morbidity and mortality. In such cases, a rapid viral detection is crucial for monitoring the clinical outcome and the antiviral treatment. In this study, we optimized a sensitive biplex TaqMan® real-time PCR for the simultaneous detection and differentiation of a partial HCMV UL97 sequence and homologous extrinsic control (HEC) in the same tube. HEC was represented by a plasmid containing a modified HCMV sequence retaining the original primer binding sites, while the probe sequence was substituted by a phylogenetically divergent one (chloroplast CF0 subunit plant gene). It was estimated that the optimal HEC concentration, which did not influence the HCMV amplification is 1,000 copies/reaction. The optimized TaqMan® PCR demonstrated high analytical sensitivity (6.97 copies/reaction, CI = 95%) and specificity (100%). Moreover, the reaction showed adequate precision (repeatability, CV = 0.03; reproducibility, CV = 0.0027) and robustness (no carry-over or cross-contamination). The diagnostic sensitivity (100%) and specificity (97.8%) were adequate for the clinical application of the molecular platform. The optimized TaqMan® real-time PCR is suitable for HCMV detection and quantitation in predisposed patients and monitoring of the applied antiviral therapy. J. Med. Virol. 88:1604-1612, 2016. © 2016 Wiley Periodicals, Inc. PMID:26890091

  4. Reduced Frequencies and Activation of Regulatory T Cells After the Treatment of HIV-1-Infected Individuals with the CCR5 Antagonist Maraviroc Are Associated with a Reduction in Viral Loads Rather Than a Direct Effect of the Drug on Regulatory T Cells.

    Science.gov (United States)

    Joedicke, Jara J; Dirks, Miriam; Esser, Stefan; Verheyen, Jens; Dittmer, Ulf

    2016-04-01

    Regulatory T cells (Tregs) play an important role in the pathogenesis of HIV-1 infection and they frequently express the chemokine receptor CCR5. We therefore investigated whether antiretroviral treatment with the CCR5 antagonist Maraviroc affected Tregs in chronically HIV-1-infected individuals. HIV-1-infected patients with high viral loads had elevated frequencies of activated Tregs in the peripheral blood compared with healthy controls. In patients successfully treated with antiretroviral drugs (undetectable viral loads), the frequency and the activation status of Tregs were comparable with healthy controls without any specific effect related to the treatment with Maraviroc. These results indicate that the control of viral replication in general rather than a direct binding of Maraviroc to CCR5-positive Tregs influences Treg responses in successfully treated chronically HIV-1-infected individuals. PMID:27035639

  5. 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...

  6. RATIONAL CUSTOMS CLEARANCE TECHNOLOGY CHOICE

    OpenAIRE

    Shramenko, N.; Andriets, V.

    2008-01-01

    Issues concerning cargo delivery efficiencyincrease by choice of rational customs clearance technology have been considered. Three possible variants of customs clearance andmethods which allow to define the most rational version of cargo delivery in international road communication based on main efficiency criteria for definite distance have been presented.

  7. Serological and Molecular Testing in Viral Hepatitis: An Update

    OpenAIRE

    Weston, Shiobhan R; Martin, Paul

    2001-01-01

    The routine serological diagnoses of the three major forms of viral hepatitis - A, B and C - as well as delta hepatitis, are important in the evaluation of acute and chronic viral hepatitis. Increasingly, molecular virology is also being used to evaluate patients with chronic hepatitis C, with genotype and viral load testing to plan therapy.

  8. Antipyrene clearance in Indian villagers.

    OpenAIRE

    Desai, N K; Sheth, U K; Mucklow, J C; Fraser, H S; Bulpitt, C J; Jones, S.W.; Dollery, C. T.

    1980-01-01

    1 Antipyrine clearance has been measured using saliva samples in 50 Maharashtrans from a village to the north of Bombay. 2 All subjects were very lean and were also anaemic probably as a result of hookworm infestation. 3 Antipyrine clearance was 36% faster than in White Londoners studied previously and more than twice as fast as in Asian immigrants living in London. 4 Clearance was 25% faster in men than in women but volume of distribution was also greater in men and mean half-lives did not d...

  9. Clearance of von Willebrand factor. : Clearance of von Willebrand factor

    OpenAIRE

    Denis, Cécile; Christophe, Olivier; Oortwijn, Beatrijs,; Lenting, Peter,

    2008-01-01

    The life cycle of von Willebrand factor (VWF) comprises a number of distinct steps, ranging from the controlled expression of the VWF gene in endothelial cells and megakaryocytes to the removal of VWF from the circulation. The various aspects of VWF clearance have been the objects of intense research in the last few years, stimulated by observations that VWF clearance is a relatively common component of the pathogenesis of type 1 von Willebrand disease (VWD). Moreover, improving the survival ...

  10. Loss of CCR7 expression on CD56(bright NK cells is associated with a CD56(dimCD16⁺ NK cell-like phenotype and correlates with HIV viral load.

    Directory of Open Access Journals (Sweden)

    Henoch S Hong

    Full Text Available NK cells are pivotal sentinels of the innate immune system and distinct subpopulations in peripheral blood have been described. A number of studies addressed HIV-induced alterations of NK cell phenotype and functionality mainly focusing on CD56(dimCD16⁺ and CD56⁻CD16⁺ NK cells. However, the impact of HIV-infection on CD56(bright NK cells is less well understood. Here we report a rise of CD56(bright NK cells in HIV-infected individuals, which lack CCR7-expression and strongly correlate with HIV viral load. CCR7⁻CD56(bright NK cells were characterized by increased cytolytic potential, higher activation states and a more differentiated phenotype. These cells thus acquired a number of features of CD56(dimCD16⁺ NK cells. Furthermore, CD56(bright NK cells from HIV patients exhibited higher degranulation levels compared to uninfected individuals. Thus, chronic HIV-infection is associated with a phenotypic and functional shift of CD56(bright NK cells, which provides a novel aspect of HIV-associated pathogenesis within the NK cell compartment.

  11. 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...... 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...

  12. 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.

  13. Measurement of nasal mucociliary clearance.

    OpenAIRE

    Corbo, G M; Foresi, A; Bonfitto, P; Mugnano, A; Agabiti, N.; Cole, P J

    1989-01-01

    The saccharin test was carried out in a randomly selected sample of schoolchildren (142 boys and 153 girls, age range 11-14 years) to determine the variability and reproducibility of the test and to assess whether it could be used as a screening test for nasal mucociliary clearance. Nasal mucociliary clearance times were analysed according to clinical history (asthma, rhinitis, asthma with rhinitis, and acute upper respiratory tract infections), laboratory findings (positive skin test respons...

  14. Inherited Disorders of Bilirubin Clearance

    OpenAIRE

    Memon, Naureen; Weinberger, Barry I; Hegyi, Thomas; Aleksunes, Lauren M

    2015-01-01

    Inherited disorders of hyperbilirubinemia may be caused by increased bilirubin production or decreased bilirubin clearance. Reduced hepatic bilirubin clearance can be due to defective 1) unconjugated bilirubin uptake and intrahepatic storage, 2) conjugation of glucuronic acid to bilirubin (e.g. Gilbert syndrome, Crigler-Najjar syndrome, Lucey-Driscoll syndrome, breast milk jaundice), 3) bilirubin excretion into bile (Dubin-Johnson syndrome), or 4) conjugated bilirubin re-uptake (Rotor syndrom...

  15. Method of mucociliary clearance assessment

    Science.gov (United States)

    Danilova, Tatiana V.; Manturov, Alexey O.; Ermakov, Igor Y.; Mareev, Gleb O.; Mareev, Oleg V.

    2016-04-01

    The article is devoted to the research capabilities of mucociliary clearance in the nasal cavity and paranasal sinuses using modern techniques of digital video recording and processing. We describe the setup and software for this method and the results of our research. Using microscope and digital camera we can provide a good method to study mucociliary clearance and by usage of special software we able to measure some characteristic of nasal mucosae and its main function.

  16. Re-entry flight clearance

    OpenAIRE

    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 models. The stability of re-entry vehicles in the presence of model uncertainties was chosen as the clearance criterion, which is represented by two mathematical criteria: worst-case eigenvalues (linear...

  17. Analysis of foot clearance in firefighters during ascent and descent of stairs.

    Science.gov (United States)

    Kesler, Richard M; Horn, Gavin P; Rosengren, Karl S; Hsiao-Wecksler, Elizabeth T

    2016-01-01

    Slips, trips, and falls are a leading cause of injury to firefighters with many injuries occurring while traversing stairs, possibly exaggerated by acute fatigue from firefighting activities and/or asymmetric load carriage. This study examined the effects that fatigue, induced by simulated firefighting activities, and hose load carriage have on foot clearance while traversing stairs. Landing and passing foot clearances for each stair during ascent and descent of a short staircase were investigated. Clearances decreased significantly (p < 0.05) post-exercise for nine of 12 ascent parameters and increased for two of eight descent parameters. Load carriage resulted in significantly decreased (p < 0.05) clearance over three ascent parameters, and one increase during descent. Decreased clearances during ascent caused by fatigue or load carriage may result in an increased trip risk. Increased clearances during descent may suggest use of a compensation strategy to ensure stair clearance or an increased risk of over-stepping during descent. PMID:26360190

  18. Impact of virus load on immunocytological and histopathological parameters during clinical chicken anemia virus (CAV) infection in poultry.

    Science.gov (United States)

    Wani, Mohd Yaqoob; Dhama, Kuldeep; Malik, Yashpal Singh

    2016-07-01

    Chicken anemia virus (CAV) is one the important pathogen affecting commercial poultry sector globally by causing mortality, production losses, immunosuppression, aggravating co-infections and vaccination failures. Here, we describe the effects of CAV load on hematological, histopathological and immunocytochemical alterations in 1-day old infected chicks. The effects of CAV on cytokine expression profiles and generation of virus specific antibody titer were also studied and compared with viral clearance in various tissues. The results clearly confirmed that peak viral load was achieved mainly in lymphoid tissues between 10 and 20 days post infection (dpi), being highest in the blood (log1010.63 ±0.87/ml) and thymus (log1010.29 ±0.94/g) followed by spleen, liver, bone marrow and bursa. The histopathology and immunoflowcytometric analysis indicated specific degeneration of T lymphoid cells in the thymus, spleen and blood at 15 dpi. While the transcript levels of interleukin (IL)-1, IL-2, IL-12 decreased at all dpi, interferon (IFN)-γ increased (3-15 fold) during early stages of infection and the appearance of virus specific antibodies were found to be strongly associated with virus clearance in all the tissues. Our findings support the immunosuppressive nature of CAV and provide the relation between the virus load in the various body tissues and the immunopathological changes during clinical CAV infections. PMID:27165537

  19. 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.

  20. Evaluation of the Aptima(®) HIV-1 Quant Dx assay for HIV-1 RNA viral load detection and quantitation in plasma of HIV-1-infected individuals: A comparison with Abbott RealTime HIV-1 assay.

    Science.gov (United States)

    Amendola, Alessandra; Pisciotta, Maria; Aleo, Loredana; Ferraioli, Valeria; Angeletti, Claudio; Capobianchi, Maria Rosaria

    2016-09-01

    The Hologic Aptima(®) HIV-1 Quant Dx assay (Aptima HIV) is a real-time transcription-mediated amplification method CE-approved for use in diagnosis and monitoring of HIV-1 infection. The analytical performance of this new assay was compared to the FDA-approved Abbott RealTime HIV-1 (RealTime). The evaluation was performed using 220 clinical plasma samples, the WHO 3rd HIV-1 International Standard, and the QCMD HIV-1 RNA EQA. Concordance on qualitative results, correlation between quantitative results, accuracy, and reproducibility of viral load data were analyzed. The ability to measure HIV-1 subtypes was assessed on the second WHO International Reference Preparation Panel for HIV-1 Subtypes. With clinical samples, inter-assay agreement for qualitative results was high (91.8%) with Cohen's kappa statistic equal to 0.836. For samples with quantitative results in both assays (n = 93), Lin's concordance correlation coefficient was 0.980 (P R(2)  > 0.970) and showed higher sensitivity compared to RealTime being able to detect HIV-1 RNA in 10 out of 10 replicates containing down to 7 cp/ml (20 IU/ml). Reproducibility was very high, even at low HIV-1 RNA values. The Aptima HIV was able to detect and accurately quantify all the main HIV-1 subtypes in both reference panels and clinical samples. Besides excellent performance, Aptima HIV shows full automation, ease of use, and improved workflow compared to RealTime. J. Med. Virol. 88:1535-1544, 2016. © 2016 Wiley Periodicals, Inc. PMID:26864171

  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...... 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. [Viral superantigens].

    Science.gov (United States)

    Us, Dürdal

    2016-07-01

    , expression of endogenous SAgs leads to thymic deletion of responding T cells (bearing Vβ6-9+ TCR) due to self-tolerance induction during the fetal life, and protects the host against future exogenous MMTV infections. The SAg of rabies virus is the N protein found in nucleocapsid structure and stimulates Vβ8+TCR-bearing T cells. The SAg-induced polyclonal activation of T cells leads to turn-off the specific immune response, to enhance the immunopathogenesis and facilitates viral transmission from the initial site of infection (the muscle tissue) to the nerve endings. In case of EBV-associated SAg that activates Vβ13+TCR-bearing T cells, it was detected that the SAg activity was not encoded by EBV itself, but instead was due to the transactivation of HERV-K18 by EBV latent membrane proteins, whose env gene encodes the SAg (Sutkowski, et al. 2001). It has been denoted that EBV-induced SAg expression plays a role in the long-term persistence and latency of virus in memory B cells, in the development of autoimmune diseases and in the oncogenesis mechanisms. The proteins which are identified as SAgs of HIV are Nef and gp120. It is believed that, the massive activation of CD4+ T cells (selectively with Vβ-12+, Vβ-5.3+ and Vβ-18+ TCRs) in early stages of infection and clonal deletion, anergy and apoptosis of bystander T cells in the late stages may be due to SAg property of Nef protein, as well as the other mechanisms. However there are some studies indicating that Nef does not act as a SAg (Lapatschek, et al. 2001). HIV gp120 glycoprotein is a B-cell SAg that binds to VH3-expressing B cell receptors and causes polyclonal B cell activation. In addition, binding of gp120 to IgE on the surface of basophiles and mast cells causes activation of those cells, secretion of high level proinflammatory mediators leading to allergic reactions and tissue damage. In a recent study, the depletion (anergy or deletion) of T cell populations bearing Vβ12+, Vβ13+ and Vβ17+ TCR have been

  3. 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.

  4. Inherited Disorders of Bilirubin Clearance

    Science.gov (United States)

    Memon, Naureen; Weinberger, Barry I; Hegyi, Thomas; Aleksunes, Lauren M

    2016-01-01

    Inherited disorders of hyperbilirubinemia may be caused by increased bilirubin production or decreased bilirubin clearance. Reduced hepatic bilirubin clearance can be due to defective 1) unconjugated bilirubin uptake and intrahepatic storage, 2) conjugation of glucuronic acid to bilirubin (e.g. Gilbert syndrome, Crigler-Najjar syndrome, Lucey-Driscoll syndrome, breast milk jaundice), 3) bilirubin excretion into bile (Dubin-Johnson syndrome), or 4) conjugated bilirubin re-uptake (Rotor syndrome). In this review, the molecular mechanisms and clinical manifestations of these conditions are described, as well as current approaches to diagnosis and therapy. PMID:26595536

  5. Inadequate clearance of translocated bacterial products in HIV-infected humanized mice.

    Directory of Open Access Journals (Sweden)

    Ursula Hofer

    2010-04-01

    Full Text Available Bacterial translocation from the gut and subsequent immune activation are hallmarks of HIV infection and are thought to determine disease progression. Intestinal barrier integrity is impaired early in acute retroviral infection, but levels of plasma lipopolysaccharide (LPS, a marker of bacterial translocation, increase only later. We examined humanized mice infected with HIV to determine if disruption of the intestinal barrier alone is responsible for elevated levels of LPS and if bacterial translocation increases immune activation. Treating uninfected mice with dextran sodium sulfate (DSS induced bacterial translocation, but did not result in elevated plasma LPS levels. DSS-induced translocation provoked LPS elevation only when phagocytic cells were depleted with clodronate liposomes (clodrolip. Macrophages of DSS-treated, HIV-negative mice phagocytosed more LPS ex vivo than those of control mice. In HIV-infected mice, however, LPS phagocytosis was insufficient to clear the translocated LPS. These conditions allowed higher levels of plasma LPS and CD8+ cell activation, which were associated with lower CD4+/CD8+ cell ratios and higher viral loads. LPS levels reflect both intestinal barrier and LPS clearance. Macrophages are essential in controlling systemic bacterial translocation, and this function might be hindered in chronic HIV infection.

  6. 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.

  7. Blockade of interferon Beta, but not interferon alpha, signaling controls persistent viral infection.

    Science.gov (United States)

    Ng, Cherie T; Sullivan, Brian M; Teijaro, John R; Lee, Andrew M; Welch, Megan; Rice, Stephanie; Sheehan, Kathleen C F; Schreiber, Robert D; Oldstone, Michael B A

    2015-05-13

    Although type I interferon (IFN-I) is thought to be beneficial against microbial infections, persistent viral infections are characterized by high interferon signatures suggesting that IFN-I signaling may promote disease pathogenesis. During persistent lymphocytic choriomeningitis virus (LCMV) infection, IFNα and IFNβ are highly induced early after infection, and blocking IFN-I receptor (IFNAR) signaling promotes virus clearance. We assessed the specific roles of IFNβ versus IFNα in controlling LCMV infection. While blockade of IFNβ alone does not alter early viral dissemination, it is important in determining lymphoid structure, lymphocyte migration, and anti-viral T cell responses that lead to accelerated virus clearance, approximating what occurs during attenuation of IFNAR signaling. Comparatively, blockade of IFNα was not associated with improved viral control, but with early dissemination of virus. Thus, despite their use of the same receptor, IFNβ and IFNα have unique and distinguishable biologic functions, with IFNβ being mainly responsible for promoting viral persistence. PMID:25974304

  8. Noninvasive clearance of airway secretions.

    Science.gov (United States)

    Hardy, K A; Anderson, B D

    1996-06-01

    Airway clearance techniques are indicated for specific diseases that have known clearance abnormalities (Table 2). Murray and others have commented that such techniques are required only for patients with a daily sputum production of greater than 30 mL. The authors have observed that patients with diseases known to cause clearance abnormalities can have sputum clearance with some techniques, such as positive expiratory pressure, autogenic drainage, and active cycle of breathing techniques, when PDPV has not been effective. Hasani et al has shown that use of the forced exhalatory technique in patients with nonproductive cough still resulted in movement of secretions proximally from all regions of the lung in patients with airway obstruction. It is therefore reasonable to consider airway clearance techniques for any patient who has a disease known to alter mucous clearance, including CF, dyskinetic cilia syndromes, and bronchiectasis from any cause. Patients with atelectasis from mucous plugs and hypersecretory states, such as asthma and chronic bronchitis, patients with pain secondary to surgical procedures, and patients with neuromuscular disease, weak cough, and abnormal patency of the airway may also benefit from the application of airway clearance techniques. Infants and children up to 3 years of age with airway clearance problems need to be treated with PDPV. Manual percussion with hands alone or a flexible face mask or cup and small mechanical vibrator/percussors, such as the ultrasonic devices, can be used. The intrapulmonary percussive ventilator shows growing promise in this area. The high-frequency oscillator is not supplied with vests of appropriate sizes for tiny babies and has not been studied in this group. Young patients with neuromuscular disease may require assisted ventilation and airway oscillations can be applied. CPAP alone has been shown to improve achievable flow rates that will increase air-liquid interactions for patients with these diseases

  9. Immune clearance of attenuated rabies virus results in neuronal survival with altered gene expression.

    Directory of Open Access Journals (Sweden)

    Emily A Gomme

    Full Text Available Rabies virus (RABV is a highly neurotropic pathogen that typically leads to mortality of infected animals and humans. The precise etiology of rabies neuropathogenesis is unknown, though it is hypothesized to be due either to neuronal death or dysfunction. Analysis of human brains post-mortem reveals surprisingly little tissue damage and neuropathology considering the dramatic clinical symptomology, supporting the neuronal dysfunction model. However, whether or not neurons survive infection and clearance and, provided they do, whether they are functionally restored to their pre-infection phenotype has not been determined in vivo for RABV, or any neurotropic virus. This is due, in part, to the absence of a permanent "mark" on once-infected cells that allow their identification long after viral clearance. Our approach to study the survival and integrity of RABV-infected neurons was to infect Cre reporter mice with recombinant RABV expressing Cre-recombinase (RABV-Cre to switch neurons constitutively expressing tdTomato (red to expression of a Cre-inducible EGFP (green, permanently marking neurons that had been infected in vivo. We used fluorescence microscopy and quantitative real-time PCR to measure the survival of neurons after viral clearance; we found that the vast majority of RABV-infected neurons survive both infection and immunological clearance. We were able to isolate these previously infected neurons by flow cytometry and assay their gene expression profiles compared to uninfected cells. We observed transcriptional changes in these "cured" neurons, predictive of decreased neurite growth and dysregulated microtubule dynamics. This suggests that viral clearance, though allowing for survival of neurons, may not restore them to their pre-infection functionality. Our data provide a proof-of-principle foundation to re-evaluate the etiology of human central nervous system diseases of unknown etiology: viruses may trigger permanent neuronal

  10. Is There a Need for Viral Load Testing to Assess Treatment Failure in HIV-Infected Patients Who Are about to Change to Tenofovir-Based First-Line Antiretroviral Therapy? Programmatic Findings from Myanmar

    Science.gov (United States)

    Thiha, Nay; Chinnakali, Palanivel; Harries, Anthony D.; Shwe, Myint; Balathandan, Thanumalaya Perumal; Thein Than Tun, Sai; Das, Mrinalini; Tin, Htay Htay; Yi, Yi; Babin, François Xavier; Lwin, Thi Thi; Clevenbergh, Philippe Albert

    2016-01-01

    Background WHO recommends that stavudine is phased out of antiretroviral therapy (ART) programmes and replaced with tenofovir (TDF) for first-line treatment. In this context, the Integrated HIV Care Program, Myanmar, evaluated patients for ART failure using HIV RNA viral load (VL) before making the change. We aimed to determine prevalence and determinants of ART failure in those on first-line treatment. Methods Patients retained on stavudine-based or zidovudine-based ART for >12 months with no clinical/immunological evidence of failure were offered VL testing from August 2012. Plasma samples were tested using real time PCR. Those with detectable VL>250 copies/ml on the first test were provided with adherence counseling and three months later a second test was performed with >1000 copies/ml indicating ART failure. We calculated the prevalence of ART failure and adjusted relative risks (aRR) to identify associated factors using log binomial regression. Results Of 4934 patients tested, 4324 (87%) had an undetectable VL at the first test while 610 patients had a VL>250 copies/ml. Of these, 502 had a second VL test, of whom 321 had undetectable VL and 181 had >1000 copies/ml signifying ART failure. There were 108 who failed to have the second test. Altogether, there were 94% with an undetectable VL, 4% with ART failure and 2% who did not follow the VL testing algorithm. Risk factors for ART failure were age 15–24 years (aRR 2.4, 95% CI: 1.5–3.8) compared to 25–44 years and previous ART in the private sector (aRR 1.6, 95% CI: 1.2–2.2) compared to the public sector. Conclusions This strategy of evaluating patients on first-line ART before changing to TDF was feasible and identified a small proportion with ART failure, and could be considered by HIV/AIDS programs in Myanmar and other countries. PMID:27505228

  11. 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. PMID:24123923

  12. 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...

  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 National Defense Department of Defense OFFICE OF THE SECRETARY OF DEFENSE SECURITY DEPARTMENT OF DEFENSE PERSONNEL SECURITY PROGRAM REGULATION Issuing Clearance and Granting Access § 154.48 Issuing clearance. (a) Authorities designated in paragraph...

  14. 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 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE SAFETY AND HEALTH SAFETY AND HEALTH STANDARDS-SURFACE METAL AND NONMETAL MINES Travelways § 56.11010 Stairstep clearance. Vertical clearance...

  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 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION AIRCRAFT AIRWORTHINESS STANDARDS: TRANSPORT CATEGORY AIRPLANES Powerplant General § 25.925 Propeller clearance. Unless smaller clearances are substantiated,...

  16. 76 FR 47917 - Lead; Clearance and Clearance Testing Requirements for the Renovation, Repair, and Painting Program

    Science.gov (United States)

    2011-08-05

    ... August 5, 2011 Part IV Environmental Protection Agency 40 CFR Part 745 Lead; Clearance and Clearance... AGENCY 40 CFR Part 745 RIN 2070-AJ57 Lead; Clearance and Clearance Testing Requirements for the... 2008 Lead Renovation, Repair, and Painting Program (RRP) rule, the EPA agreed to propose a number...

  17. Analysis of grease contamination influence on the internal radial clearance of ball bearings by thermographic inspection

    OpenAIRE

    Mišković Žarko Z.; Mitrović Radivoje M.; Stamenić Zoran V.

    2016-01-01

    One of the most important factors influencing ball bearings service life is its internal radial clearance. However, this parameter is also very complex because it depends on applied radial load and ball bearings dimensions, surface finish and manufacturing materials. Thermal condition of ball bearings also significantly affects internal radial clearance. Despite many researches performed in order to find out relevant facts about different aspects of ball be...

  18. Impaired tracheobronchial clearance in bronchiectasis.

    OpenAIRE

    Currie, D C; Pavia, D; Agnew, J E; Lopez-Vidriero, M T; Diamond, P D; Cole, P J; Clarke, S. W.

    1987-01-01

    Tracheobronchial clearance was measured by a radioaerosol technique in 12 patients with bronchiectasis, seven patients with chronic obstructive lung disease expectorating mucoid sputum daily (group X), eight patients with chronic obstructive lung disease but negligible sputum expectoration (group Y), and 10 healthy subjects. The patients with bronchiectasis all expectorated purulent sputum daily (mean wet weight 47 g/day), had reduced forced expiratory volume in one second (FEV1) (mean 47.5% ...

  19. Reduced erythrocyte susceptibility and increased host clearance of young parasites slows Plasmodium growth in a murine model of severe malaria

    Science.gov (United States)

    Khoury, David S.; Cromer, Deborah; Best, Shannon E.; James, Kylie R.; Sebina, Ismail; Haque, Ashraful; Davenport, Miles P.

    2015-05-01

    The best correlate of malaria severity in human Plasmodium falciparum (Pf) infection is the total parasite load. Pf-infected humans could control parasite loads by two mechanisms, either decreasing parasite multiplication, or increasing parasite clearance. However, few studies have directly measured these two mechanisms in vivo. Here, we have directly quantified host clearance of parasites during Plasmodium infection in mice. We transferred labelled red blood cells (RBCs) from Plasmodium infected donors into uninfected and infected recipients, and tracked the fate of donor parasites by frequent blood sampling. We then applied age-based mathematical models to characterise parasite clearance in the recipient mice. Our analyses revealed an increased clearance of parasites in infected animals, particularly parasites of a younger developmental stage. However, the major decrease in parasite multiplication in infected mice was not mediated by increased clearance alone, but was accompanied by a significant reduction in the susceptibility of RBCs to parasitisation.

  20. Progress in development of controlled-clearance pressure balance in NMIJ

    Energy Technology Data Exchange (ETDEWEB)

    Kajikawa, H; Ide, K; Kobata, T, E-mail: kajikawa.hiroaki@aist.go.j [National Metrology Institute of Japan (NMIJ), AIST, Tsukuba, Ibaraki 305-8563 (Japan)

    2010-03-01

    A new controlled-clearance pressure balance is under development with the aim of improving the hydraulic high-pressure standard up to 1 GPa. This pressure balance consists of three parts: (i) a pressure generation device up to 1 GPa, (ii) a weight-loading unit which can load/unload weights automatically and independently, (iii) a controlled-clearance piston-cylinder which is designed to allow the jacket pressure to be applied independently. Some adjustments were made for loading heavy weights on/off the piston safely, keeping them in balance, then generating the pressure stably. Stability of the generated pressure was checked for several piston-cylinders, and it was found that pressure fluctuation was less than a few parts per million. The jacket pressure coefficient of a 500 MPa controlled-clearance piston-cylinder was precisely evaluated as a function of both the system pressure and the jacket pressure.

  1. Development of the clearance level verification evaluation system. 2. Construction of the clearance data management system

    International Nuclear Information System (INIS)

    Clearance is defined as the removal of radioactive materials or radioactive objects within authorized practices from any further regulatory control by the regulatory body. In Japan, clearance level and a procedure for its verification has been introduced under the Laws and Regulations, and solid clearance wastes inspected by the national authority can be handled and recycled as normal wastes. The most prevalent type of wastes have generated from the dismantling of nuclear facilities, so the Japan Atomic Energy Agency (JAEA) has been developing the Clearance Level Verification Evaluation System (CLEVES) as a convenient tool. The Clearance Data Management System (CDMS), which is a part of CLEVES, has been developed to support measurement, evaluation, making and recording documents with clearance level verification. In addition, validation of the evaluation result of the CDMS was carried out by inputting the data of actual clearance activities in the JAEA. Clearance level verification is easily applied by using the CDMS for the clearance activities. (author)

  2. 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. PMID:27199430

  3. Polymorphisms in MDA-5 link protein function to clearance of hepatitis C virus

    OpenAIRE

    Hoffmann, Franziska; Schmidt, Andreas; Chevillotte, Meike Dittmann; Wisskirchen, Christian; Hellmuth, Johannes C.; Willms, Simone; Gilmore, Rachel H.; Glas, Jürgen; Folwaczny, Matthias; Müller, Tobias; Berg, Thomas; Spengler, Ulrich; Fitzmaurice, Karen; Kelleher, Dermot; Reisch, Nicole

    2015-01-01

    Among patients newly infected with hepatitis C virus (HCV), only 20–30 % clear the infection spontaneously. In the remaining 70 %, the infection persists causing chronic liver inflammation and disease. It is well established that polymorphisms in host genes, especially in components of the innate immune response, contribute to the phenomenon of spontaneous HCV clearance. RIG-I-like helicases such as MDA-5 are cytoplasmic sensors of viral RNA that are critical for triggering innate immune resp...

  4. Lactate clearance in cardiorespiratory emergency

    OpenAIRE

    Serena Greco; Giovanna Guiotto; Antonino Maffei; Stefania Martino; Giuseppe Romano; Fernando Schiraldi

    2007-01-01

    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), we...

  5. Experimental Investigation of Factors Influencing Operating Rotor Tip Clearance in Multistage Compressors

    Directory of Open Access Journals (Sweden)

    Reid A. Berdanier

    2015-01-01

    Full Text Available An analysis of compressor rotor tip clearance measurements using capacitance probe instrumentation is discussed for a three-stage axial compressor. Thermal variations and centrifugal effects related to rotational speed changes affect clearance heights relative to the assembled configuration. These two primary contributions to measured changes are discussed both independently and in combination. Emphasis is given to tip clearance changes due to changing loading condition and at several compressor operating speeds. Measurements show a tip clearance change approaching 0.1 mm (0.2% rotor span when comparing a near-choke operating condition to a near-stall operating condition for the third stage. Additional consideration is given to environmental contributions such as ambient temperature, for which changes in tip clearance height on the order of 0.05 mm (0.1% rotor span were noted for temperature variations of 15°C. Experimental compressor operating clearances are presented for several temperatures, operating speeds, and loading conditions, and comparisons are drawn between these measured variations and predicted changes under the same conditions.

  6. The Clearance of Cyclosporine by Hemodialysis

    OpenAIRE

    Venkataramanan, Raman; Ptachcinski, Richard J.; Burckart, Gilbert J.; YANG, SHIN L.; Starzl, Thomas E.; VAN THEIL, DAVID H.

    1984-01-01

    The pharmacokinetics of cyclosporine were studied in five liver transplant patients when they were on and off hemodialysis. There was no significant difference in the blood clearance of cyclosporine between these two periods. Less than 1 per cent of the dose of cyclosporine was recovered in the dialysate. The mean dialysis clearance was less than 1 ml/min. This represents less than 1 per cent of the total blood clearance of cyclosporine. Dosage alterations of cyclosporine during or after hemo...

  7. Revolute joints with clearance in multibody systems

    OpenAIRE

    Flores, Paulo; Ambrósio, Jorge

    2004-01-01

    A computational methodology for dynamic analysis of multibody mechanical systems with joint clearance is presented in this work. Clearances always exist in real joints in order to ensure the correct relative motion between the connected bodies being the gap associated to them a result of machining tolerance, wear, and local deformations. Clearance at different joints is the source for impact forces, resulting in wear and tear of the joints, and consequently the degradation of the system perfo...

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

    Science.gov (United States)

    Roca, Francisco J.; López-Muñoz, Azucena; Tyrkalska, Sylwia D.; Candel, Sergio; García-Moreno, Diana; Falco, Alberto; Meseguer, José

    2016-01-01

    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. PMID:27351838

  9. Viral Haemorrhagic Septicaemia Virus

    DEFF Research Database (Denmark)

    Olesen, Niels Jørgen; Skall, Helle Frank

    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....

  10. [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

  11. 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....

  12. Mucociliary clearance in early simple chronic bronchitis

    International Nuclear Information System (INIS)

    Tracheobronchial mucociliary clearance was measured in 37 patients with early simple chronic bronchitis. A non-invasive radio-aerosol technique with inhalation of 99Tcm labelled 5-μm polystyrene particles followed by assessment of radio-nuclide distribution by posterior gamma-camera scans was employed. The mucociliary clearance of the bronchitics was significantly slower than clearance of a non-smoker control group. An interim analysis of the effect of treatment with a surfactant stimulating drug, ambroxol, suggested a dosage-dependent tendency to a faster mucociliary clearance than seen in placebo-treated bronchitics. (author)

  13. 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

  14. 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...

  15. Polymorphisms in sodium taurocholate cotransporting polypeptide are not associated with hepatitis B virus clearance in Chinese Tibetans and Uygurs.

    Science.gov (United States)

    Su, Zhenzhen; Li, Yi; Liao, Yun; Cai, Bei; Chen, Jie; Zhang, Junlong; Li, Lixin; Ying, Binwu; Tao, Chuanmin; Zhao, Min; Ba, Zhu; Zhang, Zhaoxia; Wang, Lanlan

    2016-07-01

    An association between polymorphisms in the sodium taurocholate cotransporting polypeptide (NTCP) and the natural course of hepatitis B virus (HBV) infection in the Chinese Han population has been noted. However, it is not known whether these polymorphisms are associated with the risk of developing chronic HBV infection in other racial or ethnic populations. Accordingly, we conducted a candidate single nucleotide polymorphism (SNP) association study in Tibetan and Uygur HBV-infected patients. A total of 1302 subjects including 871 Tibetans and 431 Uygurs were recruited. According to their serological and clinical characteristics, each ethnic group was divided into two groups comprising spontaneous clearance individuals and persistently infected patients. Three SNPs were genotyped by a high resolution melting curve methodology. Among the SNPs, rs2296651 exhibited a minor allele frequency of viral load and HBV genotype; however, no significant differences were found in the SNP genotype distribution for each characteristic. In conclusion, the NTCP polymorphisms we identified tended to be ethnicity-dependent. For Tibetans and Uygurs, no association of the three SNPs (rs7154439, rs4646287 and rs2296651) and their haplotypes with HBV chronicity was observed. Examination of SNPs in NTCP for their specific associations with the course of HBV infection in other ethnic minority groups is now required. PMID:27051045

  16. Struggle for Space: Viral Extinction through Competition for Cells

    Science.gov (United States)

    Cuesta, José A.; Aguirre, Jacobo; Capitán, José A.; Manrubia, Susanna C.

    2011-01-01

    The design of protocols to suppress the propagation of viral infections is an enduring enterprise, especially hindered by limited knowledge of the mechanisms leading to viral extinction. Here we report on infection extinction due to intraspecific competition to infect susceptible hosts. Beneficial mutations increase the production of viral progeny, while the host cell may develop defenses against infection. For an unlimited number of host cells, a feedback runaway coevolution between host resistance and progeny production occurs. However, physical space limits the advantage that the virus obtains from increasing offspring numbers; thus, infection clearance may result from an increase in host defenses beyond a finite threshold. Our results might be relevant to devise improved control strategies in environments with mobility constraints or different geometrical properties.

  17. Effect of Guide Vane Clearance Gap on Francis Turbine Performance

    Directory of Open Access Journals (Sweden)

    Ravi Koirala

    2016-04-01

    Full Text Available Francis turbine guide vanes have pivoted support with external control mechanism, for conversion of pressure to kinetic energy and to direct them to runner vanes. This movement along the support is dependent on variation of load and flow (operating conditions. Small clearance gaps between facing plates and the upper and lower guide vane tips are available to aid this movement, through which leakage flow occurs. This secondary flow disturbs the main flow stream, resulting performance loss. Additionally, these increased horseshoe vortex, in presence of sand, when crosses through the gaps, both the surfaces are eroded. This causes further serious effect on performance and structural property by increasing gaps. This paper discusses the observation of the severity in hydropower plants and effect of clearance gaps on general performance of the Francis turbine through computational methods. It also relates the primary result with the empirical relation for leakage flow prediction. Additionally, a possible method to computationally estimate thickness depletion has also been presented. With increasing clearance gap, leakage increases, which lowers energy conversion and turbine efficiency along with larger secondary vortex.

  18. 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 HEALTH SAFETY AND HEALTH STANDARDS-SURFACE METAL AND NONMETAL MINES Drilling and Rotary Jet Piercing Drilling § 56.7018 Hand clearance....

  19. Cortisol does not inhibit prednisolone clearance.

    OpenAIRE

    Meffin, P J; Sallustio, B C; Purdie, Y J; Robson, R A; Wing, L M; Brooks, P M

    1985-01-01

    The disposition of prednisolone has been studied in eight male subjects with and without the concomitant administration of cortisol which produced plasma cortisol concentrations 10-fold higher than endogenous levels. The clearance and steady-state distribution volume of total prednisolone were increased as was the prednisolone free fraction but the clearance of unbound prednisolone was unaltered by cortisol co-administration.

  20. 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 SAFETY AND HEALTH SAFETY AND HEALTH STANDARDS-SURFACE METAL AND NONMETAL MINES Travelways § 56.11008 Restricted clearance. Where...

  1. 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 524.74 Judicial Administration BUREAU OF PRISONS, DEPARTMENT OF JUSTICE INMATE ADMISSION, CLASSIFICATION, AND TRANSFER CLASSIFICATION OF INMATES Central Inmate Monitoring (CIM) System § 524.74 Activities clearance. (a) Except as provided for in...

  2. 14 CFR 23.925 - Propeller clearance.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Propeller clearance. 23.925 Section 23.925 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION AIRCRAFT AIRWORTHINESS STANDARDS: NORMAL, UTILITY, ACROBATIC, AND COMMUTER CATEGORY AIRPLANES Powerplant General § 23.925 Propeller clearance. Unless...

  3. 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. PMID:27060566

  4. Viral Encephalitis and Epilepsy

    OpenAIRE

    J Gordon Millichap

    2008-01-01

    The role of viral meningitis in the cause of epilepsy is reviewed by researchers from Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India; and University of Malaya, Kuala Lumpur, Malaysia.

  5. To Go Viral

    CERN Document Server

    Cintron-Arias, Ariel

    2014-01-01

    Mathematical models are validated against empirical data, while examining potential indicators for an online video that went viral. We revisit some concepts of infectious disease modeling (e.g. reproductive number) and we comment on the role of model parameters that interplay in the spread of innovations. The dataset employed here provides strong evidence that the number of online views is governed by exponential growth patterns, explaining a common feature of viral videos.

  6. Human viral gastroenteritis.

    OpenAIRE

    Christensen, M.L.

    1989-01-01

    During the last 15 years, several different groups of fastidious viruses that are responsible for a large proportion of acute viral gastroenteritis cases have been discovered by the electron microscopic examination of stool specimens. This disease is one of the most prevalent and serious clinical syndromes seen around the world, especially in children. Rotaviruses, in the family Reoviridae, and fastidious fecal adenoviruses account for much of the viral gastroenteritis in infants and young ch...

  7. 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. PMID:25962882

  8. Effects of sustained exercise on pulmonary clearance of aerosolized 99mTc-DTPA

    International Nuclear Information System (INIS)

    The effects of intensive prolonged exercise on the pulmonary clearance rate of aerosolized 99mTc-labeled diethylenetriaminepentaacetate (99mTc-DTPA) and pulmonary mechanics were studied in seven healthy nonsmoking volunteers. 99mTc-DTPA clearance and pulmonary mechanics (lung volumes and compliance) were assessed before and after 75 min of constant-load exercise performed on a treadmill, corresponding to 75% of maximal O2 uptake. Because both clearance measurements were made in similar conditions of pulmonary blood flow, respiratory rate, and tidal volume, changes in clearance rate can be assumed to represent changes of alveolar epithelial permeability. After exercise, total, apical, and basal clearance were significantly increased (P less than 0.01, 0.05, and 0.05, respectively) and the increases in total clearance and tidal volume observed during exercise were significantly correlated (P less than 0.05). In contrast, no significant change was found in pulmonary mechanics. These results show that prolonged intensive exercise induces an increase in epithelial permeability, which appears to be related to the mechanical effects of sustained increased ventilation. Because no change was evidenced in pulmonary volumes or in lung elasticity, our results suggest that this increase may result from alteration of the intercellular tight junctions rather than from a surfactant deficiency

  9. 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....

  10. Influence of chronic dosing on theophylline clearance.

    OpenAIRE

    Efthimiou, H; Morgan, D. J.; Ioannides-Demos, L; Raymond, K.; McLean, A. J.

    1984-01-01

    Theophylline clearance was studied in normal healthy volunteers before and after chronic oral dosing. Oral theophylline clearance showed a significant decrease (P less than 0.001) from 59.3 +/- 6.48 ml/min (mean +/- s.e. mean, n = 10) to 48.0 +/- 6.4 ml/min. Steady-state intravenous clearance decreased by 26 +/- 2% from 55.1 +/- 7.7 ml/min to 41.0 +/- 5.96 ml/min (mean +/- s.e. mean, n = 6; P less than 0.001) at constant steady-state intravenous test concentrations (mean 15.0 +/- 1.6 microgra...

  11. SKIN KINETICS AND DERMAL CLEARANCE

    Directory of Open Access Journals (Sweden)

    Prakash Shashi

    2012-08-01

    Full Text Available Availability of several therapeutic and cosmetic formulations for topical application has made the research on skin kinetics as a topic of current interest. Topical formulations are typically meant for local effect although there is always a chance that the low molecular weight chemicals are easily transported across the skin layer and make it available in the systemic circulation. Thus there is a major concern about the transport of chemical moieties following the topical application of cosmetics and therapeutic formulations and the real time measurement of the molecules in the skin layer has become obligatory. It is well known that the properties of both drug and the excipients have identical role in determining the skin permeability of chemical moieties. In the last decade several investigations have been carried out in this filed using several in vitro and in vivo models. This review provides a brief account on the basics of skin kinetics, parameters assessed, various techniques and methods adapted in skin kinetic studies. Moreover, we have also discussed about the micro-environment inside the skin layer and the possible mechanism of drug depot formation, skin metabolism and clearance of molecules from the skin layers.

  12. Nucleotide-mediated airway clearance.

    Science.gov (United States)

    Schmid, Andreas; Clunes, Lucy A; Salathe, Mathias; Verdugo, Pedro; Dietl, Paul; Davis, C William; Tarran, Robert

    2011-01-01

    A thin layer of airway surface liquid (ASL) lines the entire surface of the lung and is the first point of contact between the lung and the environment. Surfactants contained within this layer are secreted in the alveolar region and are required to maintain a low surface tension and to prevent alveolar collapse. Mucins are secreted into the ASL throughout the respiratory tract and serve to intercept inhaled pathogens, allergens and toxins. Their removal by mucociliary clearance (MCC) is facilitated by cilia beating and hydration of the ASL by active ion transport. Throughout the lung, secretion, ion transport and cilia beating are under purinergic control. Pulmonary epithelia release ATP into the ASL which acts in an autocrine fashion on P2Y(2) (ATP) receptors. The enzymatic network describes in Chap. 2 then mounts a secondary wave of signaling by surface conversion of ATP into adenosine (ADO), which induces A(2B) (ADO) receptor-mediated responses. This chapter offers a comprehensive description of MCC and the extensive ramifications of the purinergic signaling network on pulmonary surfaces. PMID:21560046

  13. Does Viral Marketing really Effective?

    OpenAIRE

    Chien, Ho-shen

    2012-01-01

    Abstract In this article, we examine the effectiveness of viral marketing toward young adults since the majority of Internet users are in this age group. It is also noted that we will only focus on video type of viral messages, which is the most common way to utilized viral marketing for firms. We will discuss how viral video influence consumer behavior in terms of brand images, brand choice, user experience and working memory in this paper. Our results illustrated viral video helps major...

  14. Deposition of aerosols and bronchial clearance measurements

    International Nuclear Information System (INIS)

    A special inhalative device is described for reproducible deposition patterns of radioactive aerosols to measure mucociliary and tussive clearance and to evaluate the effect of drugs on the bronchial tree is described. Additive actions on mucus transport exist between β2-agonists and theophylline, but not incombination with inhalative quarternary ammonium compounds (ipatropium and oxitropium bromide). Mucolytics are generally less effective on mucociliary clearance than β2-agonists and theophylline, positive, negative and nonresponders are ofter seen due to the different viscoelastic properties of the mucus. Mucus transport is more than mucociliary clearance. Two-phase gas/liquid movement and coughing are also important transport mechanisms for bronchial mucus. Therefore, bronchodilators enhance mucus transport by increasing airway patency, which increases total and regional air flow and improves cough clearance. (orig.)

  15. Compressor airfoil tip clearance optimization system

    Energy Technology Data Exchange (ETDEWEB)

    Little, David A.; Pu, Zhengxiang

    2015-08-18

    A compressor airfoil tip clearance optimization system for reducing a gap between a tip of a compressor airfoil and a radially adjacent component of a turbine engine is disclosed. The turbine engine may include ID and OD flowpath boundaries configured to minimize compressor airfoil tip clearances during turbine engine operation in cooperation with one or more clearance reduction systems that are configured to move the rotor assembly axially to reduce tip clearance. The configurations of the ID and OD flowpath boundaries enhance the effectiveness of the axial movement of the rotor assembly, which includes movement of the ID flowpath boundary. During operation of the turbine engine, the rotor assembly may be moved axially to increase the efficiency of the turbine engine.

  16. Clearance of germ granules in the soma

    OpenAIRE

    Sugimoto, Asako

    2009-01-01

    Germ granules are ribonucleoprotein complexes specifically segregated into germ cell lineages in diverse organisms. Recent studies indicate that multiple mechanisms are involved in the clearance of germ granules and their components in somatic cells in Caenorhabditis elegans embryos.

  17. 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 is...

  18. The curious world of apoptotic cell clearance

    OpenAIRE

    Weitzman, Jonathan B

    2004-01-01

    Analysis of knockout mice has brought into question the previously proposed role of the phosphatidylserine receptor (Ptdsr) in the clearance of apoptotic cell corpses, and has suggested important functions in regulating differentiation and inflammation.

  19. Exclusion, exemption, clearance European Union approach

    International Nuclear Information System (INIS)

    The presentation overviews the following issues: Euratom Basic Safety Standards; administrative requirements; radiation protection of the population. Scope of the Standards: natural radiation sources; exclusion. Exemption; Clearance; Import of radioactive scrap metal

  20. Blade by Blade Tip Clearance Measurement

    OpenAIRE

    A. G. Sheard

    2011-01-01

    This paper describes a capacitance-based tip clearance measurement system which engineers have used in the most demanding turbine test applications. The capacitance probe has survived extended use in a major European gas turbine manufacturer's high-temperature demonstrator unit, where it functioned reliably at a turbine entry temperature in excess of 1800 degrees Kelvin. This paper explores blade by blade tip clearance measurement techniques and examines probe performance under laboratory con...

  1. Clearance of inhaled particles in ankylosing spondylitis.

    OpenAIRE

    Farquhar, D R; Chamberlain, M. J.; McCain, G A; Morgan, W K

    1989-01-01

    Patients with ankylosing spondylitis may uncommonly develop apical fibrobullous lung disease, the cause of which is unknown. It is postulated here that rigidity of the thoracic cage leads to reduced apical clearance of inhaled particles and may thereby predispose to chronic infection. Deposition and clearance of inhaled technetium-99m sulphur colloid particles were studied in eight male patients with ankylosing spondylitis who had chest wall rigidity (mean (SD) chest expansion 1.8 (1.07) cm) ...

  2. Reduction of antipyrine clearance in psoriasis.

    OpenAIRE

    Marsden, J R; Williams, F M; Keys, B; Rawlins, M D; Shuster, S

    1984-01-01

    Antipyrine clearance was determined in 41 psoriatics and age-sex matched controls, using sequential measurements of salivary concentration. Antipyrine clearance and elimination rate constant were less in psoriatics (P less than 0.05) and apparent volumes of distribution were similar. These differences were greater between female psoriatics and controls (P less than 0.025; P less than 0.05) and the differences between male psoriatics and controls were not significant. Correlation of simultaneo...

  3. Extreme contagion in global habitat clearance

    OpenAIRE

    Boakes, Elizabeth H.; Mace, Georgina M; Philip J K McGowan; Fuller, Richard A.

    2009-01-01

    Habitat clearance remains the major cause of biodiversity loss, with consequences for ecosystem services and for people. In response to this, many global conservation schemes direct funds to regions with high rates of recent habitat destruction, though some also emphasize the conservation of remaining large tracts of intact habitat. If the pattern of habitat clearance is highly contagious, the latter approach will help prevent destructive processes gaining a foothold in areas of contiguous in...

  4. Hemodialysis clearance of metronidazole and its metabolites.

    OpenAIRE

    Lau, A. H.; Chang, C W; Sabatini, S

    1986-01-01

    Metronidazole is now being used with increasing frequency for various infectious conditions in patients with renal failure. It is commonly administered to septic patients who have developed acute renal failure requiring hemodialysis. The hemodialysis clearances of metronidazole and its metabolites were evaluated in nine renal failure patients on maintenance hemodialysis. The mean +/- standard deviation clearance and the extraction ratio were 106.9 +/- 16.3 ml/min and 0.65 +/- 0.08, respective...

  5. [Viral hepatitis in travellers].

    Science.gov (United States)

    Abreu, Cândida

    2007-01-01

    Considering the geographical asymmetric distribution of viral hepatitis A, B and E, having a much higher prevalence in the less developed world, travellers from developed countries are exposed to a considerable and often underestimated risk of hepatitis infection. In fact a significant percentage of viral hepatitis occurring in developed countries is travel related. This results from globalization and increased mobility from tourism, international work, humanitarian and religious missions or other travel related activities. Several studies published in Europe and North America shown that more than 50% of reported cases of hepatitis A are travel related. On the other hand frequent outbreaks of hepatitis A and E in specific geographic areas raise the risk of infection in these restricted zones and that should be clearly identified. Selected aspects related with the distribution of hepatitis A, B and E are reviewed, particularly the situation in Portugal according to the published studies, as well as relevant clinical manifestations and differential diagnosis of viral hepatitis. Basic prevention rules considering enteric transmitted hepatitis (hepatitis A and hepatitis E) and parenteral transmitted (hepatitis B) are reviewed as well as hepatitis A and B immunoprophylaxis. Common clinical situations and daily practice "pre travel" advice issues are discussed according to WHO/CDC recommendations and the Portuguese National Vaccination Program. Implications from near future availability of a hepatitis E vaccine, a currently in phase 2 trial, are highlighted. Potential indications for travellers to endemic countries like India, Nepal and some regions of China, where up to 30% of sporadic cases of acute viral hepatitis are caused by hepatitis E virus, are considered. Continued epidemiological surveillance for viral hepatitis is essential to recognize and control possible outbreaks, but also to identify new viral hepatitis agents that may emerge as important global health

  6. 19 CFR 4.61 - Requirements for clearance.

    Science.gov (United States)

    2010-04-01

    ... 19 Customs Duties 1 2010-04-01 2010-04-01 false Requirements for clearance. 4.61 Section 4.61 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT OF THE TREASURY VESSELS IN FOREIGN AND DOMESTIC TRADES Foreign Clearances § 4.61 Requirements for clearance. (a) Application for clearance. A...

  7. 48 CFR 801.602-76 - Business clearance review.

    Science.gov (United States)

    2010-10-01

    ... obtain a business clearance review prior to award of any contract, task or delivery order, or blanket... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Business clearance review... Authority, and Responsibilities 801.602-76 Business clearance review. (a) A business clearance review is...

  8. Viral diseases of the rabbit.

    Science.gov (United States)

    Krogstad, Aric P; Simpson, Janet E; Korte, Scott W

    2005-01-01

    Viral disease in the rabbit is encountered infrequently by the clinical practitioner; however, several viral diseases were reported to occur in this species. Viral diseases that are described in the rabbit primarily may affect the integument, gastrointestinal tract or, central nervous system or maybe multi-systemic in nature. Rabbit viral diseases range from oral papillomatosis, with benign clinical signs, to rabbit hemorrhagic disease and myxomatosis, which may result in significant clinical disease and mortality. The wild rabbit may serve as a reservoir for disease transmission for many of these viral agents. In general, treatment of viral disease in the rabbit is supportive in nature. PMID:15585192

  9. BIOMARKERS OF VIRAL EXPOSURE

    Science.gov (United States)

    Viral and protozoan pathogens associated with raw sludge can cause encephalitis, gastroenteritis, hepatitis, myocarditis, and a number of other diseases. Raw sludge that has been treated to reduce these pathogens can be used for land application according to the regulations spec...

  10. WATERBORNE VIRAL GASTROENTERITIS

    Science.gov (United States)

    In the study of human gastroenteritis, the use of electron microscopy and related techniques has led to the identification of new viral agents which had previously escaped detection by routine cell-culture procedures. Efforts to characterize and further study these agents are cur...

  11. Viral Haemorrhagic Septicaemia

    OpenAIRE

    Institute, Marine

    2011-01-01

    This leaflet gives information on viral haemorrhagic septicaemia (VHS). VHS is caused by a single stranded RNA virus of the family Rhabdoviridae, genus Novirhabdoviridae. VHS is listed as a non-exotic disease under EU Directive 2006/88/EC, and is notifiable in Ireland, according to S.I. No. 261 of 2008.

  12. BOVINE VIRAL DIARRHEA VIRUSES

    Science.gov (United States)

    Bovine viral diarrhea virus (BVDV) is an umbrella term for two species of viruses, BVDV1 and BVDV2, within the Pestivirus genus of the Flavivirus family. BVDV viruses are further subclassified as cytopathic and noncytopathic based on their activity in cultured epithelial cells. Noncytopathic BVDV p...

  13. Effect of blade tip configuration on tip clearance loss of a centrifugal impeller

    Science.gov (United States)

    Ishida, Masahiro; Ueki, Hironobu; Senoo, Yasutoshi

    1989-06-01

    The effect of blade tip configuration on the tip clearance loss was examined experimentally using an unshrouded centrifugal impeller with backward-leaning blades. Tips with rounded edges, sharp square edges, and edges with end plates were tested. The observed tip clearance effects could be theoretically predicted by assuming reasonable values of the contraction coefficent alpha = 0.91 for the round edge, 0.73 for the sharp square edge, and 0.53 for the end-plate edge. The impeller efficiency was improved by about 1.5 point by reducing the contraction coefficient from 0.91 to 0.53. The effect of contraction coefficient on impeller efficiency depends on the ratio of leakage loss to the tip clearance loss. Improved efficiency for impellers with highly loaded blades is expected from reducing the contraction coefficient.

  14. Regulatory T cells control diabetes without compromising acute anti-viral defense☆

    Science.gov (United States)

    Sachithanantham, Sowbarnika; Dave, Amy; Rodriguez-Calvo, Teresa; Miller, Jacqueline; von Herrath, Matthias

    2016-01-01

    While previous reports have demonstrated the efficacy of regulatory T cell therapy in the prevention of diabetes, systemic immunocompromise and Treg instability remain key safety concerns. Here we examined the influence of induced Treg (iTreg) cell therapy on anti-viral host defense and autoimmune T cell responses during acute viral infection in a murine model of autoimmune diabetes. Protective transfers of iTregs maintained IL-10 expression, and expanded in vivo and controlled diabetes, despite losing FoxP3 expression. Adoptive transfer of iTregs affected neither the primary anti-viral CD8 T cell response nor viral clearance, although a significant and sustained suppression of CD4 T cell responses was observed. Following acute viral clearance, iTregs transferred early suppressed both CD4 and CD8 T cell responses, which resulted in the reversion of diabetes. These observations indicate that iTregs suppress local autoimmune processes while preserving the immunocompetent host's ability to combat acute viral infection. PMID:24858581

  15. 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....

  16. 75 FR 25037 - Lead; Clearance and Clearance Testing Requirements for the Renovation, Repair, and Painting Program

    Science.gov (United States)

    2010-05-06

    ... Protection Agency 40 CFR Part 745 Lead; Clearance and Clearance Testing Requirements for the Renovation..., 2010 / Proposed Rules#0;#0; ] ENVIRONMENTAL PROTECTION AGENCY 40 CFR Part 745 RIN 2070-AJ57 Lead... 2008 Lead Renovation, Repair, and Painting Program (RRP) rule that established accreditation,...

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

    Science.gov (United States)

    2010-07-07

    ... established in the Federal Register of May 6, 2010 (75 FR 25038) (FRL-8823-5). In that document, EPA proposed... AGENCY 40 CFR Part 745 RIN 2070-AJ57 Lead; Clearance and Clearance Testing Requirements for the... Federal Register of May 6, 2010, concerning several revisions to the 2008 Lead Renovation, Repair,...

  18. 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...

  19. The DNA load of six high-risk human papillomavirus types and its association with cervical lesions

    OpenAIRE

    Río Ospina, Luisa del; Soto de León, Sara; Camargo, Milena; Moreno Pérez, Darwin Andrés; Sánchez, Ricardo; Pérez Prados, Antonio; Patarroyo, Manuel Elkin; Patarroyo, Manuel Alfonso

    2015-01-01

    Background: Analysing human papillomavirus (HPV) viral load is important in determining the risk of developing cervical cancer (CC); most knowledge to date regarding HPV viral load and cervical lesions has been related to HPV-16. This study evaluated the association between the viral load of the six most prevalent high-risk viral types in Colombia and cervical intraepithelial neoplasia (CIN) frequency. Methods: 114 women without CIN and 59 women having CIN confirmed by colposcopy, all of them...

  20. Viral Hepatitis: A through E and Beyond

    Science.gov (United States)

    ... causes viral hepatitis? Clinical Trials What is viral hepatitis? Viral hepatitis is inflammation of the liver caused by ... and adenovirus. [ Top ] What are the symptoms of viral hepatitis? Symptoms include jaundice, which causes a yellowing of ...

  1. Dengue viral infections

    OpenAIRE

    Malavige, G; Fernando, S; Fernando, D; Seneviratne, S.

    2004-01-01

    Dengue viral infections are one of the most important mosquito borne diseases in the world. They may be asymptomatic or may give rise to undifferentiated fever, dengue fever, dengue haemorrhagic fever (DHF), or dengue shock syndrome. Annually, 100 million cases of dengue fever and half a million cases of DHF occur worldwide. Ninety percent of DHF subjects are children less than 15 years of age. At present, dengue is endemic in 112 countries in the world. No vaccine is available for preventing...

  2. Viral Interferon Regulatory Factors

    OpenAIRE

    Lee, Hye-Ra; Kim, Myung Hee; Lee, Jong-Soo; Liang, Chengyu; Jung, Jae U.

    2009-01-01

    Upon viral infection, the major defensive strategy employed by the host immune system is the activation of the interferon (IFN)-mediated antiviral pathway, which is overseen by IFN regulatory factors (IRFs). In order to complete their life cycles, viruses must find a way to modulate the host IFN-mediated immune response. Kaposi's sarcoma-associated herpesvirus (KSHV), a human tumor-inducing herpesvirus, has developed a unique mechanism for antagonizing cellular IFN-mediated antiviral activity...

  3. Transport of viral specimens.

    OpenAIRE

    Johnson, F. B.

    1990-01-01

    The diagnosis of viral infections by culture relies on the collection of proper specimens, proper care to protect the virus in the specimens from environmental damage, and use of an adequate transport system to maintain virus activity. Collection of specimens with swabs that are toxic to either virus or cell culture should be avoided. A variety of transport media have been formulated, beginning with early bacteriological transport media. Certain swab-tube combinations have proven to be both e...

  4. Engineering influenza viral vectors

    OpenAIRE

    Li, Junwei; Arévalo, Maria T; Zeng, Mingtao

    2013-01-01

    The influenza virus is a respiratory pathogen with a negative-sense, segmented RNA genome. Construction of recombinant influenza viruses in the laboratory was reported starting in the 1980s. Within a short period of time, pioneer researchers had devised methods that made it possible to construct influenza viral vectors from cDNA plasmid systems. Herein, we discuss the evolution of influenza virus reverse genetics, from helper virus-dependent systems, to helper virus-independent 17-plasmid sys...

  5. Clearance Laboratory - Capability and measurement sensitivity

    International Nuclear Information System (INIS)

    A new low-level Clearance Laboratory has been built at the Risoe-site. Building materials with a low content of naturally occurring radionuclides have been used. To minimize transport of radon gas from soil into the laboratory the foundation has been supplied with a membrane. The laboratory has been equipped with two high-efficiency germanium detectors. These detectors will be used for clearance measurements on the predicted amount of 15,000 - 18,000 tonnes of non-active or nearly non-active materials, which will originate from the decommissioning of all the nuclear facilities at the Risoe-site. They will be used also for clearance measurements on buildings and land. Objects and materials to be measured for clearance are placed on a rotation table that can carry up to one tonne and can rotate once a minute to simulate some averaging of inhomogeneously distributed activity. Sensitivity and background measurements reveal that measuring times of 20 - 50 minutes would normally be sufficient to detect radionuclide concentrations of only a small fraction of the nuclide-specific clearance levels with a sufficiently low uncertainty. Probability calculations of the measurement capacity of the Clearance Laboratory indicate that the mean value of the total measuring time for all materials that potentially can be cleared would be 13 years with a 95% probability of being less than 25 years. The mean value of the annual amount of materials that can be measured in the laboratory is 600 tonnes with a 95% probability of being less than 1,200 tonnes. If needed, there is room for additional measuring systems to increase the capacity of the laboratory. (au)

  6. 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.

  7. Viral membrane fusion

    International Nuclear Information System (INIS)

    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

  8. DYNAMICS OF VIRAL ADVERTISING

    Directory of Open Access Journals (Sweden)

    Ayşe Binay KURULTAY

    2012-04-01

    Full Text Available Digital technologies have heightened the debate on convergence where technologies, corporations and people [target audiences] meet. New media has become a new meeting place and a social platform for people. As more brands choose to employ relationship marketing strategies that emphasize consumer’s experience with the brand, it is inevitable that they explore opportunities to connect with their target audiences in this new meeting place. Thus, user-created content and electronic word of mouth [eWOM] have become important concepts for influential and noteworthy advertising campaigns in this new medium. The aim of this study is to understand the dynamics of viral marketing campaigns and to identify the strategies that make viral advertising successful. International cases, such as brand applications of 3D Mapping Projections are used to understand the relationship between cutting-edge digital art and their use in advertisements. Recent Turkish viral ad campaigns such as Profilo’s “O Tabak Bitecek!” [Finish everything on your plate] and Turkish Airlines Miles and Smiles’ “İnanılmaz Evlenme Teklifi” [Unbelievable Proposal] disseminated through social networks are used as cases to identify the message strategies used in making these advertisements successful.

  9. Mucociliary clearance from the calf lung.

    OpenAIRE

    C.D. Jones

    1983-01-01

    Mucociliary clearance rate constants for ten calves were obtained using Technetium 99m-sulphur colloid complex. The mean rate constant measured at the lung for all calves was 0.012 (+/- 0.009) min-1 (half-life 58 minutes). The clearance rate constants obtained from measurements made at the larynx were higher (0.02 +/- 0.007 min-1), although not significantly higher, than those determined from measurements taken at the lung. The constants can be used to predict the particle burden on the lungs...

  10. Effects of airborne pollutants on mucociliary clearance.

    OpenAIRE

    Wolff, R K

    1986-01-01

    The mucociliary clearance system is a first line of defense against inhaled agents, and so its compromise can adversely affect health. The purpose of this paper is to provide a review of data on the effect of in vivo air pollutant exposures on the clearance of test particles from airways. Data from both animals and humans are compared whenever possible, so that estimates of human health effects may be made. Mechanisms of action are also discussed, presenting the view that for low level exposu...

  11. Nasal mucociliary clearance in patients with tracheostomy

    OpenAIRE

    Yadav, S. P. S.; Janab, Khan Shariq; Singh, Jagat; Ranga, Rupender K.

    2003-01-01

    Nasal mucociliary clearance (NMC) time was estimated in 30 tracheostomized patients (24 males & 6 females) in the age group of 13–55 years which was 7.04±0.38 minutes: The patients suffering from nose and paranasal sinus disorders; taking drugs like bromhexine; undergoing radiotherapy and smokers were excluded from the study. The nasal mucociliary clearance in 30 age & sex matched healthy controls was 9.16±0.62 minutes. The NMC was found to he significantly lowered in patients with tracheosto...

  12. Impact of Glycation on Antibody Clearance

    OpenAIRE

    Yang, Jane; Primack, Ronya; Frohn, Mike; Wang, Wei; Luan, Peng; Retter, Marc W.; Flynn, Gregory C.

    2014-01-01

    Glycation of therapeutic proteins occurs during mammalian cell culture expression and upon administration to patients. Since the chemical attachment of mannose or other sugars via a chemical linker has been shown to increase a protein’s clearance rate in mice through the mannose receptor, we explored the effect of mannose glycation on the clearance of an IgG in mice. An IgG decorated with high levels of mannose (~18 mol/mol protein) through glycation did not clear faster in mice than the unde...

  13. Glycerol clearance in alcoholic liver disease.

    OpenAIRE

    Johnston, D G; Alberti, K. G.; Wright, R; Blain, P G

    1982-01-01

    Glycerol clearance was studied by a primed dose-constant infusion technique in 14 patients with alcoholic liver disease and six normal control subjects. Fasting blood glycerol concentrations were raised in the alcoholic subjects (0.09 +/- 0.01 vs 0.06 +/- 0.01 mumol/l, p less than 0.05) and glycerol clearance was impaired (24.5 +/- 1.9 vs 37.5 +/- 3.2 ml/kg/min, p less than 0.005). Endogenous production rate of glycerol and distribution space at steady state were similar in alcoholic and cont...

  14. 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. PMID:22640851

  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. HIV–1 Dynamics: A Reappraisal of Host and Viral Factors, as well as Methodological Issues

    Directory of Open Access Journals (Sweden)

    Jianming Tang

    2012-10-01

    Full Text Available The dynamics of HIV–1 viremia is a complex and evolving landscape with clinical and epidemiological (public health implications. Most studies have relied on the use of set–point viral load (VL as a readily available proxy of viral dynamics to assess host and viral correlates. This review highlights recent findings from population–based studies of set–point VL, focusing primarily on robust data related to host genetics. A comprehensive understanding of viral dynamics will clearly need to consider both host and viral characteristics, with close attention to (i the timing of VL measurements, (ii the biology of viral evolution, (iii compartments of active viral replication, (iv the transmission source partner as the immediate past microenvironment, and (v proper application of statistical models.

  17. Clearance of a Mucus Plug

    Science.gov (United States)

    Bian, Shiyao; Zheng, Ying; Grotberg, James B.

    2008-11-01

    Mucus plugging may occur in pulmonary airways in asthma, chronic obstructive pulmonary disease (COPD) and cystic fibrosis. How to clear the mucus plug is essential and of fundamental importance. Mucus is known to have a yield stress and a mucus plug behaves like a solid plug when the applied stresses are below its yield stress τy. When the local stresses reaches τy, the plug starts to move and can be cleared out of the lung. It is then of great importance to examine how the mucus plug deforms and what is the minimum pressure required to initiate its movement. The present study used the finite element method (FEM) to study the stress distribution and deformation of a solid mucus plug under different pressure loads using ANSYS software. The maximum shear stress is found to occur near the rear transition region of the plug, which can lead to local yielding and flow. The critical pressure increases linearly with the plug length and asymptotes when the plug length is larger than the half channel width. Experimentally a mucus simulant is used to study the process of plug deformation and critical pressure difference required for the plug to propagate. Consistently, the fracture is observed to start at the rear transition region where the plug core connects the films. However, the critical pressure is observed to be dependent on not only the plug length but also the interfacial shape.

  18. Modelling Virus and Antibody Dynamics during Dengue Virus Infection Suggests a Role for Antibody in Virus Clearance

    Science.gov (United States)

    Clapham, Hannah E; Dorigatti, Ilaria; Simmons, Cameron P; Ferguson, Neil M

    2016-01-01

    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. PMID:27213681

  19. Anti-EBOV GP IgGs Lacking α1-3-Galactose and Neu5Gc Prolong Survival and Decrease Blood Viral Load in EBOV-Infected Guinea Pigs

    Science.gov (United States)

    Reynard, Olivier; Jacquot, Frédéric; Evanno, Gwénaëlle; Mai, Hoa Le; Martinet, Bernard; Duvaux, Odile; Bach, Jean-Marie; Conchon, Sophie; Judor, Jean-Paul; Perota, Andrea; Lagutina, Irina; Duchi, Roberto; Lazzari, Giovanna; Le Berre, Ludmilla; Perreault, Hélène; Lheriteau, Elsa; Raoul, Hervé; Volchkov, Viktor; Galli, Cesare; Soulillou, Jean-Paul

    2016-01-01

    Polyclonal xenogenic IgGs, although having been used in the prevention and cure of severe infectious diseases, are highly immunogenic, which may restrict their usage in new applications such as Ebola hemorrhagic fever. IgG glycans display powerful xenogeneic antigens in humans, for example α1–3 Galactose and the glycolyl form of neuraminic acid Neu5Gc, and IgGs deprived of these key sugar epitopes may represent an advantage for passive immunotherapy. In this paper, we explored whether low immunogenicity IgGs had a protective effect on a guinea pig model of Ebola virus (EBOV) infection. For this purpose, a double knock-out pig lacking α1–3 Galactose and Neu5Gc was immunized against virus-like particles displaying surface EBOV glycoprotein GP. Following purification from serum, hyper-immune polyclonal IgGs were obtained, exhibiting an anti-EBOV GP titer of 1:100,000 and a virus neutralizing titer of 1:100. Guinea pigs were injected intramuscularly with purified IgGs on day 0 and day 3 post-EBOV infection. Compared to control animals treated with IgGs from non-immunized double KO pigs, the anti-EBOV IgGs-treated animals exhibited a significantly prolonged survival and a decreased virus load in blood on day 3. The data obtained indicated that IgGs lacking α1–3 Galactose and Neu5Gc, two highly immunogenic epitopes in humans, have a protective effect upon EBOV infection. PMID:27280712

  20. The host immune response in respiratory virus infection: balancing virus clearance and immunopathology.

    Science.gov (United States)

    Newton, Amy H; Cardani, Amber; Braciale, Thomas J

    2016-07-01

    The respiratory tract is constantly exposed to the external environment, and therefore, must be equipped to respond to and eliminate pathogens. Viral clearance and resolution of infection requires a complex, multi-faceted response initiated by resident respiratory tract cells and innate immune cells and ultimately resolved by adaptive immune cells. Although an effective immune response to eliminate viral pathogens is essential, a prolonged or exaggerated response can damage the respiratory tract. Immune-mediated pulmonary damage is manifested clinically in a variety of ways depending on location and extent of injury. Thus, the antiviral immune response represents a balancing act between the elimination of virus and immune-mediated pulmonary injury. In this review, we highlight major components of the host response to acute viral infection and their role in contributing to mitigating respiratory damage. We also briefly describe common clinical manifestations of respiratory viral infection and morphological correlates. The continuing threat posed by pandemic influenza as well as the emergence of novel respiratory viruses also capable of producing severe acute lung injury such as SARS-CoV, MERS-CoV, and enterovirus D68, highlights the need for an understanding of the immune mechanisms that contribute to virus elimination and immune-mediated injury. PMID:26965109

  1. 32 CFR 154.16 - Security clearance.

    Science.gov (United States)

    2010-07-01

    ..., such as guards, emergency service personnel, firemen, doctors, nurses, police, ambulance drivers, or... shall be accomplished in accordance with 32 CFR part 159. The investigative requirement shall be the... be processed for a security clearance in accordance with 32 CFR part 353 and the provisions of...

  2. Uptake and clearance of uranium by misgurnus

    International Nuclear Information System (INIS)

    The author studied the bioconcentration and clearance of uranium in misgurnus and determined bioconcentration factors (BCF) as well as uptake and depuration rate constants. The test was performed under semi-static conditions. The depuration of uranium was best described by a two-compartment first order kinetic model

  3. Clearance of seborrhoeic keratoses with topical dobesilate

    OpenAIRE

    Cuevas, Pedro; Angulo, Javier; Salgüero, Irene; Giménez-Gallego, Guillermo

    2012-01-01

    A patient with two seborrhoeic keratoses in the face received a single daily application of dobesilate cream during 6 months. Dobesilate achieved complete clearance of the seborrhoeic keratosis lesions with good cosmoses, suggesting that this compound is a safe and efficient candidate in the treatment of seborrhoeic keratoses.

  4. 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 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE SAFETY AND HEALTH SAFETY AND HEALTH STANDARDS-UNDERGROUND METAL AND NONMETAL MINES Travelways and Escapeways Travelways-Surface and Underground §...

  5. 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 HEALTH SAFETY AND HEALTH STANDARDS-UNDERGROUND METAL AND NONMETAL MINES Drilling and Rotary Jet Piercing Drilling-Surface Only § 57.7018...

  6. 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 HEALTH SAFETY AND HEALTH STANDARDS-UNDERGROUND METAL AND NONMETAL MINES Drilling and Rotary Jet Piercing Drilling-Underground Only § 57.7028...

  7. 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 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE SAFETY AND HEALTH SAFETY AND HEALTH STANDARDS-UNDERGROUND METAL AND NONMETAL MINES Travelways and Escapeways Travelways-Surface and Underground...

  8. Clearance measurements on a hot cell building

    International Nuclear Information System (INIS)

    A former hot-cell facility of Siemens AG, in which dose rates in excess of 99 Sv were still prevailing in 1999, was decontaminated and subjected, except for the basement, to radiological clearance measurements. The authorities released the building for demolition in November 2004. Demolition of the upper stories of the building was started immediately afterwards using conventional techniques. For decontamination, the actual cells themselves - rooms with one-meter-thick concrete walls - had been dismantled using diamond saws and the resulting concrete blocks sent off-site for further processing. Contamination was removed from the remaining ceilings, walls and floors by knocking off the plaster and milling away the screed. Material samples were taken to confirm that decontamination had been successful. It was only then that the actual clearance measurements began. The individual rooms were grouped together into logically arranged ''clearance steps'' to simplify documentation. Most of the measurements were performed by in-situ gamma spectroscopy, with and without collimation. In addition, numerous material specimens were removed, direct surface measurements performed using contamination monitors, and wipe tests carried out. Records were made of all measurements and sorted according to clearance steps before being submitted to the competent authorities as an application for release from regulatory control. After the authorities had taken their own verification measurements they issued their approval for release. (orig.)

  9. 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

    2015-01-01

    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. PMID:26627732

  10. Tracheobronchial clearance studies in the guinea pig

    International Nuclear Information System (INIS)

    Tracheobronchial clearance in guinea pigs exposed to relatively monodisperse aerosols was studied. Two new techniques were developed which enabled tagging of polystyrene particles with 198Au and with a fluorescent dye. A procedure was also developed to generate polystyrene particles with a vibrating orifice generator. Seventy animals were exposed via inhalation to relatively monodisperse polystyrene aerosols. Following exposure, animals were radioactively counted at regular intervals, sacrificed at predetermined times, and the lungs were removed, inflated to a standard pressure, frozen in liquid nitrogen, and freeze-dried. The freeze-dried lungs were sectioned completely, examined with a fluorescent microscope, and measurements were made of airway diameters in which particles were found. The results indicated a significant penetration of particles to the distal bronchioles and air spaces for 7.9 μm (MMD) particles and a lesser, though still significant, penetration for 10.3 μm (MMD) particles. An anatomical model for guinea pig lung morphology was used to classify particular ranges of airway diameters into zones. These zones were used to specify a compartmental model for lung clearance and the experimental particle distributions were categorized using this model. Equations were then developed describing the compartmental clearance. Rate constants were then obtained and used to predict airway transport rates in specific lung generations.The predicted transport rates ranged from approximately 0.001 mm/min in the distal bronchioles to approximately 8 mm/min in the trachea. These values agree with previous models for airway transport rates, and are consistent with experimental determinations of tracheal transport rates. Transit times were calculated and the results indicate a 24 hr clearance time for tracheobronchial clearance in the guinea pig

  11. Dengue viral infections

    OpenAIRE

    Gurugama Padmalal; Garg Pankaj; Perera Jennifer; Wijewickrama Ananda; Seneviratne Suranjith

    2010-01-01

    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...

  12. Viral and radiation carcinogenesis

    International Nuclear Information System (INIS)

    The studies included under this project are concerned with basic biological and biochemical indices that may aid in the detection and understanding of the primary effects of radiation insult and the initiation of the observed malignancies. A primary objective is to determine the role of virus in radiation-induced malignancies and in the process to identify those changes which might serve to monitor the oncogenic process. This report includes in vitro studies of the cytotoxic and mutagenic potential of 244Pu, cell-mediated immunity in beagles exposed to 238PuO2 and characterization of a porcine radiation-induced viral DNA polymerase

  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. Standardizing the measurement of parasite clearance in falciparum malaria: the parasite clearance estimator

    OpenAIRE

    Flegg Jennifer A; Guerin Philippe J; White Nicholas J; Stepniewska Kasia

    2011-01-01

    Abstract Background A significant reduction in parasite clearance rates following artesunate treatment of falciparum malaria, and increased failure rates following artemisinin combination treatments (ACT), signaled emergent artemisinin resistance in Western Cambodia. Accurate measurement of parasite clearance is therefore essential to assess the spread of artemisinin resistance in Plasmodium falciparum. The slope of the log-parasitaemia versus time relationship is considered to be the most ro...

  15. Effect of inhibitors of prostaglandin synthesis on hepatic drug clearance.

    OpenAIRE

    Feely, J; Wood, A. J.

    1983-01-01

    The effect of inhibition of prostaglandin synthesis on the systemic clearance of indocyanine green and antipyrine was studied in seven subjects. Antipyrine clearance was not altered by indomethacin suggesting that oxidative metabolism was not affected. Both aspirin and indomethacin decreased the clearance of indocyanine green presumably by reducing liver blood flow. These results suggest that an effect of inhibitors of prostaglandin synthesis on hepatic drug clearance is likely to be confined...

  16. 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 ...

  17. 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. PMID:23642871

  18. Viral marketing as epidemiological model

    OpenAIRE

    Rodrigues, Helena Sofia; Fonseca, Manuel José

    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...

  19. 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.

  20. The clearance of albumin microspheres from an intramuscular injection site

    International Nuclear Information System (INIS)

    Human serum albumin microspheres of three different diameters were radiolabelled with indium-111, and a suspension injected into rabbit thigh muscle. Clearance from the intramuscular site was monitored for 2 weeks using gamma scintigraphy. The clearance rates were compared with the injection site clearance of non-biodegradable polystyrene microspheres. (U.K.)

  1. 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... AIRWORTHINESS STANDARDS: NORMAL CATEGORY ROTORCRAFT Design and Construction Rotors § 27.661 Rotor blade clearance. There must be enough clearance between the rotor blades and other parts of the structure...

  2. 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... AIRWORTHINESS STANDARDS: TRANSPORT CATEGORY ROTORCRAFT Design and Construction Rotors § 29.661 Rotor blade clearance. There must be enough clearance between the rotor blades and other parts of the structure...

  3. 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 ADMINISTRATION, DEPARTMENT OF TRANSPORTATION CONFIDENTIAL BUSINESS INFORMATION Pt. 512, App. F Appendix F to Part 512—OMB Clearance The OMB clearance...

  4. 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 no larger than is necessary to insure...

  5. Wear analysis of revolute joints with clearance in multibody systems

    Science.gov (United States)

    Bai, ZhengFeng; Zhao, Yang; Wang, XingGui

    2013-08-01

    In this work, the prediction of wear for revolute joint with clearance in multibody systems is investigated using a computational methodology. The contact model in clearance joint is established using a new hybrid nonlinear contact force model and the friction effect is considered by using a modified Coulomb friction model. The dynamics model of multibody system with clearance is established using dynamic segmentation modeling method and the computational process for wear analysis of clearance joint in multibody systems is presented. The main computational process for wear analysis of clearance joint includes two steps, which are dynamics analysis and wear analysis. The dynamics simulation of multibody system with revolute clearance joint is carried out and the contact forces are drawn and used to calculate the wear amount of revolute clearance joint based on the Archard's wear model. Finally, a four-bar multibody mechanical system with revolute clearance joint is used as numerical example application to perform the simulation and show the dynamics responses and wear characteristics of multibody systems with revolute clearance joint. The main results of this work indicate that the contact between the joint elements is wider and more frequent in some specific regions and the wear phenomenon is not regular around the joint surface, which causes the clearance size increase non-regularly after clearance joint wear. This work presents an effective method to predict wear of revolute joint with clearance in multibody systems.

  6. 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 .

  7. 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...

  8. 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

  9. A Stochastic Model of Latently Infected Cell Reactivation and Viral Blip Generation in Treated HIV Patients

    OpenAIRE

    Conway, Jessica M; Coombs, Daniel

    2011-01-01

    Motivated by viral persistence in HIV+ patients on long-term anti-retroviral treatment (ART), we present a stochastic model of HIV viral dynamics in the blood stream. We consider the hypothesis that the residual viremia in patients on ART can be explained principally by the activation of cells latently infected by HIV before the initiation of ART and that viral blips (clinically-observed short periods of detectable viral load) represent large deviations from the mean. We model the system as a...

  10. Oral immune regulation: a novel method for modulation of anti-viral immunity.

    Science.gov (United States)

    Margalit, Maya; Ilan, Yaron

    2004-12-01

    Chronic viral infections, including hepatitis B and C and human immunodeficiency virus (HIV) infections, afflict a significant part of the world's population. In many of these diseases, chronicity has been linked to defective anti-viral immunity that damages host tissues without producing viral clearance. Currently available therapeutic measures for chronic viral infections are limited. Oral immune regulation, the manipulation of immune responses towards antigens by their oral administration, is a relatively simple and antigen-specific immune-modulatory tool. Recent evidence suggests that induction of oral immune-regulation towards viral antigens may entail a complex immune effect, characterized by simultaneous enhancement and suppression of different elements of the immune response in a manner that benefits the host. Such manipulation of the immune response towards viruses may achieve a combination of upregulated specific anti-viral immunity and inhibition of immune-mediated damage. Oral immune regulation may prove to be an important addition to the available therapeutic arsenal for chronic viral infections. PMID:15567096

  11. 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.

  12. Stormwater runoff drives viral community composition changes in inland freshwaters

    Directory of Open Access Journals (Sweden)

    Kurt E. Williamson

    2014-03-01

    Full Text Available Storm events impact freshwater microbial communities by transporting terrestrial viruses and other microbes to freshwater systems, and by potentially resuspending microbes from bottom sediments. The magnitude of these impacts on freshwater ecosystems is unknown and largely unexplored. Field studies carried out at two discrete sites in coastal Virginia (USA were used to characterize the viral load carried by runoff and to test the hypothesis that terrestrial viruses introduced through stormwater runoff change the composition of freshwater microbial communities. Field data gathered from an agricultural watershed indicated that primary runoff can contain viral densities approximating those of receiving waters. Furthermore, viruses attached to suspended colloids made up a large fraction of the total load, particularly in early stages of the storm. At a second field site (stormwater retention pond, RAPD-PCR profiling showed that the viral community of the pond changed dramatically over the course of two intense storms while relatively little change was observed over similar time scales in the absence of disturbance. Comparisons of planktonic and particle-associated viral communities revealed two completely distinct communities, suggesting that particle-associated viruses represent a potentially large and overlooked portion of aquatic viral abundance and diversity. Our findings show that stormwater runoff can quickly change the composition of freshwater microbial communities. Based on these findings, increased storms in the coastal mid-Atlantic region predicted by most climate change models will likely have important impacts on the structure and function of local freshwater microbial communities.

  13. Viral Load and Infection Status of HPV Type 58 in Cervical Cancer in Eastern of Guangdong Province%HPV58型在粤东地区宫颈癌中的病毒含量和感染状态研究

    Institute of Scientific and Technical Information of China (English)

    周莉; 魏晓龙; 黄萍; 关明飞

    2013-01-01

    [Purpose]To establish a sensitive and stable method for measuring human papilloma virus (HPV) type 58 infection status of cervical cancer patients in eastern region of Guangdong province.[Methods] HPV58E2/E6 genes were amplified,PCR products were purified and linked to T vector,and constructed the standard plasmid. HPV5S viral load and infection status of 30 cervical cancer patients and 40 controls were detected. [ Results ] The standard plasmid of realtime fluorescence quantitative PCR for detecting HPV5& E2/E6 fragments was stable and sensitive. HPV58 infection rate and viral load in cervical carcinoma were higher than those of controls. Further, HPV58 infection status were integrated (66.67%) and mixed status (33.33%) in cervical cancer,which were different from controls. [Conclusion] The standard plasmid of fluorescence quantitative PCR is a high sensitivity and stability method to detect HPV58 virus load and infection status,and integration status is the main infection status of HPV58 in the cervical cancer patients in eastern region of Guangdong province.%[目的]建立灵敏而稳定的人乳头状瘤病毒(human papillomavirus,HPV) 58型病毒含量与整合状态检测方法,并探讨HPV58型在我国粤东地区妇女宫颈癌中的感染特征.[方法] PCR扩增HPV58E2和E6基因,PCR产物纯化,连接入T载体,构建标准品;检测30例宫颈癌和40例对照组织样本中HPV58的病毒含量和整合状态.[结果]成功构建含有HPV58 E2或E6片段的T载体质粒作为检测HPV58型的病毒含量和判断感染状态标准品.HPV58型在宫颈癌中的感染率和病毒含量较正常宫颈组织均高,并且HPV58在粤东地区宫颈癌中的感染状态以整合型(66.67%)和混合型(33.33%)为主,和正常宫颈组织中感染状态分布有显著差异.[结论]采用荧光定量PCR法所建立的HPV58型病毒含量和整合状态的检测方法具有灵敏性和稳定性,HPV58型在粤东地区宫颈癌中的感染以整合状态为主.

  14. Nuclear targeting of viral and non-viral DNA.

    Science.gov (United States)

    Chowdhury, E H

    2009-07-01

    The nuclear envelope presents a major barrier to transgene delivery and expression using a non-viral vector. Virus is capable of overcoming the barrier to deliver their genetic materials efficiently into the nucleus by virtue of the specialized protein components with the unique amino acid sequences recognizing cellular nuclear transport machinery. However, considering the safety issues in the clinical gene therapy for treating critical human diseases, non-viral systems are highly promising compared with their viral counterparts. This review summarizes the progress on exploring the nuclear traffic mechanisms for the prominent viral vectors and the technological innovations for the nuclear delivery of non-viral DNA by mimicking those natural processes evolved for the viruses as well as for many cellular proteins. PMID:19552613

  15. Analysis of grease contamination influence on the internal radial clearance of ball bearings by thermographic inspection

    Directory of Open Access Journals (Sweden)

    Mišković Žarko Z.

    2016-01-01

    Full Text Available One of the most important factors influencing ball bearings service life is its internal radial clearance. However, this parameter is also very complex because it depends on applied radial load and ball bearings dimensions, surface finish and manufacturing materials. Thermal condition of ball bearings also significantly affects internal radial clearance. Despite many researches performed in order to find out relevant facts about different aspects of ball bearings thermal behaviour, only few of them are dealing with the real working conditions, where high concentration of solid contaminant particles is present. That’s why the main goal of research presented in this paper was to establish statistically significant correlation between ball bearings temperatures, their working time and concentration of contaminant particles in their grease. Because of especially difficult working conditions, the typical conveyor idlers bearings were selected as representative test samples and appropriate solid particles from open pit coal mines were used as artificial contaminants. Applied experimental methodology included thermographic inspection, as well as usage of custom designed test rig for ball bearings service life testing. Finally, by obtained experimental data processing in advanced software, statistically significant mathematical correlation between mentioned bearings characteristics was determined and applied in commonly used internal radial clearance equation. That is the most important contribution of performed research - the new equation and methodology for ball bearings internal clearance determination which could be used for eventual improvement of existing bearings service life equations. [Projekat Ministarstva nauke Republike Srbije, br. TR35029 i br. TR14033

  16. Nasal mucociliary clearance in coal mine workers

    Energy Technology Data Exchange (ETDEWEB)

    Cinar, F.; Beder, L. [Karaelmas University, Kozlu Zonguldak (Turkey)

    2004-06-01

    The purpose of this study was to analyze the effect of coal dust particles on nasal mucociliary function in coal mine workers. Using the saccharin method, nasal mucociliary clearance was determined for 77 subjects, of which 39 who worked in a coal mine were actively exposed to coal dust whereas 38 were unexposed control subjects. The measurements were performed in the coal mine, at the level of 170 m below sea level. The average saccharin nasal transit time in coal mine workers, 12.61 (SD: 4.30) minutes, is longer, than that of the control subjects, 10.97 (SD: 3.22). Although the findings of this study demonstrate that the coal particles affect the nasal mucociliary clearance, the difference in saccharin nasal transit time between the two groups (exposed vs unexposed) is not statistically significant (P = 0.063).

  17. Viral Hemorrhagic Fever Diagnostics.

    Science.gov (United States)

    Racsa, Lori D; Kraft, Colleen S; Olinger, Gene G; Hensley, Lisa E

    2016-01-15

    There are 4 families of viruses that cause viral hemorrhagic fever (VHF), including Filoviridae. Ebola virus is one virus within the family Filoviridae and the cause of the current outbreak of VHF in West Africa. VHF-endemic areas are found throughout the world, yet traditional diagnosis of VHF has been performed in large reference laboratories centered in Europe and the United States. The large amount of capital needed, as well as highly trained and skilled personnel, has limited the availability of diagnostics in endemic areas except in conjunction with governmental and nongovernmental entities. However, rapid diagnosis of VHF is essential to efforts that will limit outbreaks. In addition, increased global travel suggests VHF diagnoses may be made outside of the endemic areas. Thus, understanding how to diagnose VHF is imperative for laboratories worldwide. This article reviews traditional and current diagnostic modalities for VHF. PMID:26354968

  18. Pulmonary clearance of vasoactive intestinal peptide.

    OpenAIRE

    Barrowcliffe, M P; Morice, A; Jones, J G; Sever, P S

    1986-01-01

    Vasoactive intestinal peptide causes bronchodilatation when given intravenously but is less effective in both animals and man when given by inhalation. This difference may be due to poor transit of the peptide across the bronchial epithelium. To test this hypothesis pulmonary clearance of radiolabelled vasoactive intestinal peptide was measured in Sprague Dawley rats and compared with that of pertechnetate (TcO4-) and diethylene triamine pentaacetate (DTPA). Despite a molecular weight (MW) of...

  19. Bomb strike experiment for mine clearance operations

    OpenAIRE

    Ray, Gregory P.

    2006-01-01

    The Bomb Strike Experiment for Mine Countermeasure Operations, currently sponsored through the Office of Naval Research mine impact burial prediction project, is part of a multi-year, comprehensive effort aimed at enhancing the Navyâ s fleet naval mine clearance capability and success. The investigation discussed in this paper examines the experimental and theoretical characteristics of a rigid body falling through the air, water, and sediment column at high speed. Several experiments were ...

  20. Stereoselective renal clearance of pindolol in humans.

    OpenAIRE

    Hsyu, P H; Giacomini, K M

    1985-01-01

    In this study, pindolol, a beta-adrenoceptor blocking agent marketed as a racemic mixture, was used as a model compound to investigate stereoselective renal clearance of organic cations in human beings. Six normal subjects received an oral dose of 20 mg racemic pindolol. Heart rate and blood pressure were measured throughout the study. A stereospecific high performance liquid chromatographic procedure was used to quantitate the concentrations of d- and l-pindolol in plasma and urine. Renal cl...

  1. Antipyrine clearance during occupational exposure to styrene.

    OpenAIRE

    Døssing, M

    1983-01-01

    Animal experiments have indicated that styrene, which is a widely used organic solvent, may induce the microsomal enzyme function of the liver. Thirteen workers with long-term exposure to styrene in a polyester plant were investigated. They worked at air concentrations about the maximal allowed time-weighted average concentration of styrene in most Western countries (50 ppm). The clearance of antipyrine was determined from saliva concentrations before and after three weeks free of exposure an...

  2. Clearance of bronchial secretions after major surgery

    OpenAIRE

    Leur, Johannes Peter van de

    2005-01-01

    Minimally invasive airway suctioning is equally effective as routine endotracheal suctioning but results in less suction related adverse events, less recollection of suctioning and less stress. Thus, although it cannot be employed in all situations, minimally invasive airway suctioning should be the “default setting” for mucus clearance in ICU-patients. Special suction catheters should be marketed that do not pass the distal tip of the endotracheal tube. Alternatively, standard catheters can ...

  3. Promoter clearance by RNA polymerase II

    OpenAIRE

    Luse, Donal S.

    2012-01-01

    Many changes must occur to the RNA polymerase II (pol II) transcription complex as it makes the transition from initiation into transcript elongation. During this intermediate phase of transcription, contact with initiation factors is lost and stable association with the nascent transcript is established. These changes collectively comprise promoter clearance. Once the transcript elongation complex has reached a point where its properties are indistinguishable from those of complexes with muc...

  4. Hemodialysis clearance of intravenously administered ribavirin.

    OpenAIRE

    Kramer, T H; Gaar, G G; Ray, C G; Minnich, L; Copeland, J G; Connor, J. D.

    1990-01-01

    A patient with an implanted artificial heart, acute, anuric renal failure, and disseminated influenza virus type A infection received intravenous ribavirin. Drug elimination by hemodialysis was measured. Plasma dialysis clearance averaged 93.9 +/- 8.6 ml/min. The maximum amount of ribavirin removed from the body during one period of hemodialysis was 79.1 mg. Ribavirin is not removed in important quantities by hemodialysis.

  5. Immune clearance of highly pathogenic SIV infection

    OpenAIRE

    Hansen, Scott G.; Piatak, Michael; Ventura, Abigail B.; Hughes, Colette M.; Gilbride, Roxanne M.; Ford, Julia C.; Oswald, Kelli; Shoemaker, Rebecca; Li, Yuan; Matthew S. Lewis; Gilliam, Awbrey N.; Xu, Guangwu; Whizin, Nathan; Burwitz, Benjamin J; Planer, Shannon L.

    2013-01-01

    Established infections with the human and simian immunodeficiency viruses (HIV, SIV) are thought to be permanent with even the most effective immune responses and anti-retroviral therapies (ART) only able to control, but not clear, these infections 1–4 . Whether the residual virus that maintains these infections is vulnerable to clearance is a question of central importance to the future management of millions of HIV-infected individuals. We recently reported that ~50% of rhesus macaques (RM)...

  6. 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.

  7. Establishing exemption and clearance criteria by the regulatory authority

    International Nuclear Information System (INIS)

    This Project work discusses the relationship between the concepts of exemption and clearance, and their practical use in the overall scheme of regulatory control of practices. It also discusses how exemptions and clearance is established and the scope of its applications for regulatory control. The concept of general clearance levels for any type of material and any possible pathway of disposal is also introduced in this work. Guidance of the Group of Experts establishing scenarios for general clearance, parameter values, and a nuclide-specific list of calculated clearance levels is also presented. Regulatory authorities are required to develop guidance on exemption and clearance levels to assist licensees and registrants to know which practices and sources within practices are exempted from regulatory control and those to be cleared from further controls. Exemption and clearance levels are tools for assisting the Regulatory Authority to optimize the use of resources. (author)

  8. Relationship Dynamics and Partner Beliefs About Viral Suppression: A Longitudinal Study of Male Couples Living with HIV/AIDS (The Duo Project).

    Science.gov (United States)

    Conroy, Amy A; Gamarel, Kristi E; Neilands, Torsten B; Dilworth, Samantha E; Darbes, Lynae A; Johnson, Mallory O

    2016-07-01

    Accurate beliefs about partners' viral suppression are important for HIV prevention and care. We fit multilevel mixed effects logistic regression models to examine associations between partners' viral suppression beliefs and objective HIV RNA viral load tests, and whether relationship dynamics were associated with accurate viral suppression beliefs over time. Male couples (N = 266 couples) with at least one HIV-positive partner on antiretroviral therapy completed five assessments over 2 years. Half of the 407 HIV-positive partners were virally suppressed. Of the 40 % who had inaccurate viral load beliefs, 80 % assumed their partner was suppressed. The odds of having accurate viral load beliefs decreased over time (OR = 0.83; p = 0.042). Within-couple differences in dyadic adjustment (OR = 0.66; p < 0.01) and commitment (OR = 0.82; p = 0.022) were negatively associated with accurate viral load beliefs. Beliefs about a partner's viral load may factor into sexual decision-making and social support. Couple-based approaches are warranted to improve knowledge of partners' viral load. PMID:27150895

  9. 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; Røntved, C.M.; Uttenthal, Åse; Rønsholt, L.; Alexandersen, Søren

    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...... replication 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...... 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...

  10. Multiple Inhibitory Pathways Contribute to Lung CD8+ T Cell Impairment and Protect against Immunopathology during Acute Viral Respiratory Infection.

    Science.gov (United States)

    Erickson, John J; Rogers, Meredith C; Tollefson, Sharon J; Boyd, Kelli L; Williams, John V

    2016-07-01

    Viruses are frequent causes of lower respiratory infection (LRI). Programmed cell death-1 (PD-1) signaling contributes to pulmonary CD8(+) T cell (TCD8) functional impairment during acute viral LRI, but the role of TCD8 impairment in viral clearance and immunopathology is unclear. We now find that human metapneumovirus infection induces virus-specific lung TCD8 that fail to produce effector cytokines or degranulate late postinfection, with minimally increased function even in the absence of PD-1 signaling. Impaired lung TCD8 upregulated multiple inhibitory receptors, including PD-1, lymphocyte activation gene 3 (LAG-3), T cell Ig mucin 3, and 2B4. Moreover, coexpression of these receptors continued to increase even after viral clearance, with most virus-specific lung TCD8 expressing three or more inhibitory receptors on day 14 postinfection. Viral infection also increased expression of inhibitory ligands by both airway epithelial cells and APCs, further establishing an inhibitory environment. In vitro Ab blockade revealed that multiple inhibitory receptors contribute to TCD8 impairment induced by either human metapneumovirus or influenza virus infection. In vivo blockade of T cell Ig mucin 3 signaling failed to enhance TCD8 function or reduce viral titers. However, blockade of LAG-3 in PD-1-deficient mice restored TCD8 effector functions but increased lung pathology, indicating that LAG-3 mediates lung TCD8 impairment in vivo and contributes to protection from immunopathology during viral clearance. These results demonstrate that an orchestrated network of pathways modifies lung TCD8 functionality during viral LRI, with PD-1 and LAG-3 serving prominent roles. Lung TCD8 impairment may prevent immunopathology but also contributes to recurrent lung infections. PMID:27259857

  11. 干扰素α-1b联合恩替卡韦治疗高病毒载量慢性乙型肝炎疗效评价%Efficacy of interferon alfa-1b combined with entecavir in treatment of patients with chronic hepatitis B and high serum viral load

    Institute of Scientific and Technical Information of China (English)

    占国清; 李芳; 李儒贵; 刘翔; 谭华炳

    2016-01-01

    目的:探讨干扰素α-1b联合恩替卡韦(ETV)治疗高病毒载量慢性乙型肝炎(CHB)患者的临床疗效。方法92例高病毒载量(血清HBV DNA≥1×107 IU/ml)CHB患者被分为观察组48例和对照组44例。对照组采用干扰素α-1b治疗,观察组采用干扰素α-1b联合ETV治疗,疗程48 w。比较两组治疗后第12、24、48 w血清丙氨酸氨基转移酶(ALT)复常率、HBV DNA不可检出率、HBeAg阴转率和HBeAg转换率。采用ELISA法检测血清乙型肝炎病毒标记物;使用自动生化分析仪检测肝功能指标;采用荧光定量PCR法检测HBV DNA。结果在治疗第24 w和48 w时,观察组血清ALT复常率分别为68.8%和91.7%,显著高于对照组的34.1%和63.6%(P<0.01);在治疗第12 w、24 w和48 w时,观察组血清HBV DNA不可检测率分别为45.8%、72.9%和87.5%,显著高于对照组的11.4%、31.8%和47.7%(P<0.01);在治疗第48 w时,观察组HBeAg阴转率和HBeAg转换率分别为67.6%和62.2%,显著高于对照组的42.9%和37.1%(P<0.05)。结论干扰素α-1b联合ETV治疗血清高病毒载量的CHB患者疗效优于单用干扰素α-1b。%Objective To investigate the clinical efficacy of interferon alfa-1b combined with entecavir (ETV)in treatment of patients with chronic hepatitis B (CHB) and high serum viral loads. Methods 92 patients with CHB and high serum viral load (HBV DNA≥1×107 IU/ml) were divided into observation group (n=48) and control group (n=44). Patients in the control group were treated with interferon alfa-1b,and patients in the observation group were treated with interferon alfa-1b combined with ETV. The treatment course in two groups lasted for 48 weeks. The recovery rates of serum alanine aminotransferase (ALT),rates of serum HBV DNA loss, negative rates of HBeAg and the conversion rates of HBeAg to anti-HBe were compared at 12,24 and 48 weeks. Serum HBV markers and HBV DNA levels were routinely detected. Results The

  12. Clearance of extractables and leachables from single-use technologies via ultrafiltration/diafiltration operations.

    Science.gov (United States)

    Magarian, Nicholas; Lee, Kate; Nagpal, Kunal; Skidmore, Ken; Mahajan, Ekta

    2016-05-01

    Quantifying the clearance of extractables and leachables (E/L) throughout ultrafiltration/diafiltration (UFDF) operations allows for greater flexibility in the implementation of single-use technologies in steps upstream of the UFDF process. A proof-of-concept study was completed in which the clearance of 7 E/L from single-use technologies (trimethylsilanol, hexanoic acid, butyrolactone, t-butyl alcohol, caprolactam, acetonitrile, and benzyl alcohol) in four representative proteins were measured and monitored during the UFDF process using quantitative NMR. This study demonstrated that the defined E/L spiked into a variety of protein solutions can be cleared to 1 ppm, which is explained in detail. The overall clearance trend observed for both buffer control and protein-containing solutions resembled the ideal clearance trend where no apparent interactions were observed between E/L with the protein, UFDF system, or with other defined E/L which may be present in the system. Additionally, the UFDF system is capable of clearing these potential E/L from single-use technologies below 1 ppm irrespective of initial concentrations in the load (1,000 or 100 ppm), independently from the type of protein. In general, mass recoveries were within ±15% of each spiked compound in protein solutions and their respective buffer controls, suggesting spiked E/L do not interact strongly with protein. By demonstrating the product independent clearance trends of the spiked E/L across UFDF, these results will contribute to the simplification of the E/L toxicology assessment and allow modular manufacturing approach for single-use technologies in biopharmaceutical manufacturing. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:718-724, 2016. PMID:27071939

  13. Insulated Foamy Viral Vectors.

    Science.gov (United States)

    Browning, Diana L; Collins, Casey P; Hocum, Jonah D; Leap, David J; Rae, Dustin T; Trobridge, Grant D

    2016-03-01

    Retroviral vector-mediated gene therapy is promising, but genotoxicity has limited its use in the clinic. Genotoxicity is highly dependent on the retroviral vector used, and foamy viral (FV) vectors appear relatively safe. However, internal promoters may still potentially activate nearby genes. We developed insulated FV vectors, using four previously described insulators: a version of the well-studied chicken hypersensitivity site 4 insulator (650cHS4), two synthetic CCCTC-binding factor (CTCF)-based insulators, and an insulator based on the CCAAT box-binding transcription factor/nuclear factor I (7xCTF/NF1). We directly compared these insulators for enhancer-blocking activity, effect on FV vector titer, and fidelity of transfer to both proviral long terminal repeats. The synthetic CTCF-based insulators had the strongest insulating activity, but reduced titers significantly. The 7xCTF/NF1 insulator did not reduce titers but had weak insulating activity. The 650cHS4-insulated FV vector was identified as the overall most promising vector. Uninsulated and 650cHS4-insulated FV vectors were both significantly less genotoxic than gammaretroviral vectors. Integration sites were evaluated in cord blood CD34(+) cells and the 650cHS4-insulated FV vector had fewer hotspots compared with an uninsulated FV vector. These data suggest that insulated FV vectors are promising for hematopoietic stem cell gene therapy. PMID:26715244

  14. 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.

  15. 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

  16. Clearance and release from control - An international perspective

    International Nuclear Information System (INIS)

    This paper tries to give an overview of the clearance, or release from regulatory control, on an international scale, including some of those countries where clearance has become or is about to become vital for D and D. The emphasis lies on the impact of clearance, and in particular of differences between clearance levels of various countries, on D and D. Relevance of clearance for D and D of nuclear installations Clearance is an essential part of waste management (or more general, material management) in nuclear installations, and in particular during the decommissioning phase where waste streams continues to arise. Of course, the relevance of clearance in a particular country depends on a number of factors, like: availability of a final repository and its price; prevailing decommissioning strategy; number of nuclear installations reaching decommissioning phase. This small selection of reasons why clearance may be of varying importance for different countries may already suffice to illustrate why up to now clearance has been developed and implemented in quite different ways. If one thinks of additional reasons that may influence clearance, like politics, the public opinion, availability of funds etc., the situation becomes even more complex. It is, however safe to draw the conclusion that countries with a certain number of nuclear installations which have been or will soon be shut down or which are already in the decommissioning phase will need to implement provisions for clearance. This has indeed been the case with countries like the UK, Germany, the USA, Sweden, and a number of others. It is not essential for clearance levels to be exactly equal between various countries. They may differ as long as the difference is not too large, e.g. the values fall into the same order of magnitude. This is the reason why for example Germany has no problems with clearance levels which differ from the EU recommendation RP 122 partially adopted in a number of EU countries

  17. 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...

  18. Evaluation of viral inactivation of pseudorabies virus, encephalomyocarditis virus, bovine viral diarrhea virus and porcine parvovirus in pancreatin of porcine origin.

    Science.gov (United States)

    Caruso, C; Gobbi, E; Biosa, T; Andra', M; Cavallazzi, U; Masoero, L

    2014-11-01

    Pancreatin is a substance containing enzymes, principally amylase, lipase, and protease. It is obtained from bovine or porcine pancreas and used in the treatment of pancreatic endocrine insufficiency in humans. Regulations and safety concerns mandate viral clearance (virus removal or inactivation) in biopharmaceuticals such as pancreatin. A virus validation study was performed to evaluate virus clearance achieved in the final step of drying under vacuum by testing a panel of four animal viruses: Pseudorabies virus (PRV), Encephalomyocarditis virus (EMCV), Bovine viral diarrhea virus (BVDV), and Porcine parvovirus (PPV). Because of the product's virucidal effect and high cytotoxicity, the starting material was diluted to a ratio of 0.67 g of dried pancreatin resuspended in 13.5 mL of cell culture medium followed by a 50-fold dilution in cell culture medium before spiking. After heating at 60±1°C for 5 h, the samples were diluted about 5-fold in cell culture medium and titered by the plaque assay method. The virus reduction factor ranged from 5.59 (for PPV) to 7.07 (for EMCV) and no viral plaque was observed, indicating that the process step was effective in the reduction and removal of virus contamination. Though no virus contamination events in pancreatin have been reported to date, evaluation of the production process for its ability to inactivate and/or remove virus contamination, particularly from zoonotic viral agents such as hepatitis E virus and Norovirus considered emerging pathogens, is necessary to ensure the viral safety of animal-derived biopharmaceuticals. PMID:25110118

  19. Investigations of renal clearance in nuclear medicine

    International Nuclear Information System (INIS)

    Comparative investigations of PAH- and inulin-clearance and results of investigations with J-131-hippurate and Cr-51-EDTA, which were performed by a partly screened whole body counter including measurements of activity retention of blood samples, are showing good correlation. If the radio-isotope nephrography is worked out together with the decreased retention curve, separate results of the function of both kidneys can be given. Modifications which were tried to analyze a small part of the retention curve instead of the whole body are inaccurate, if they are below 300 ml/min. (orig.)

  20. Carbamazepine Clearance and Seizure Stability during Pregnancy

    OpenAIRE

    Johnson, Emily L.; Stowe, Zachary N.; Ritchie, James C; Newport, D. Jeffrey; Newman, Melanee L.; Knight, Bettina; Pennell, Page B

    2014-01-01

    The aims of this study were to characterize the alterations in total and free carbamazepine (CBZ) and total and free carbamazepine-epoxide (CBZ-EPO) clearances during pregnancy; to calculate the change in free fractions of CBZ and CBZ-EPO during pregnancy; and to determine whether seizure worsening is associated with a low ratio to non-pregnant baseline concentration of total or free CBZ or CBZ-EPO. Women on CBZ were enrolled before conception or during pregnancy in this prospective, observat...

  1. Study of blade clearance effects on centrifugal pumps

    Science.gov (United States)

    Hoshide, R. K.; Nielson, C. E.

    1972-01-01

    A program of analysis, design, fabrication, and testing has been conducted to develop and experimentally verify analytical models to predict the effects of impeller blade clearance on centrifugal pumps. The effect of tip clearance on pump efficiency, and the relationship between the head coefficient and torque loss with tip clearance was established. Analysis were performed to determine the cost variation in design, manufacture, and test that would occur between unshrouded and shrouded impellers. An impeller, representative of typical rocket engine impellers, was modified by removing its front shroud to permit variation of its blade clearances. It was tested in water with special instrumentation to provide measurements of blade surface pressures during operation. Pump performance data were obtained from tests at various impeller tip clearances. Blade pressure data were obtained at the nominal tip clearance. Comparisons of predicted and measured data are given.

  2. 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...

  3. 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 ...

  4. Neuroanatomy goes viral!

    Science.gov (United States)

    Nassi, Jonathan J; Cepko, Constance L; Born, Richard T; Beier, Kevin T

    2015-01-01

    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 spread, and extending

  5. 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

  6. Viral infection, inflammation and schizophrenia

    OpenAIRE

    Kneeland, Rachel E.; Fatemi, S. Hossein

    2012-01-01

    Schizophrenia is a severe neurodevelopmental disorder with genetic and environmental etiologies. Prenatal viral/bacterial infections and inflammation play major roles in the genesis of schizophrenia. In this review, we describe a viral model of schizophrenia tested in mice whereby the offspring of mice prenatally infected with influenza at E7, E9, E16, and E18 show significant gene, protein, and brain structural abnormalities postnatally. Similarly, we describe data on rodents exposed to bact...

  7. Viral diseases of northern ungulates

    OpenAIRE

    Frölich, K.

    2000-01-01

    This paper describes viral diseases reported in northern ungulates and those that are a potential threat to these species. The following diseases are discussed: bovine viral diarrhoea/mucosal disease (BVD/MD), alphaherpesvirus infections, malignant catarrhal fever (MCF), poxvirus infections, parainfluenza type 3 virus infection, Alvsborg disease, foot-and-mouth disease, epizootic haemorrhage disease of deer and bluetongue disease, rabies, respiratory syncytial virus infection, adenovirus infe...

  8. EC and IAEA guidance on exemption and clearance levels and implications on clearance in Germany

    Energy Technology Data Exchange (ETDEWEB)

    Thierfeldt, S.; Woerlen, S.; Barthel, R. [Brenk Systemplanung GmbH, Aachen (Germany)

    2009-07-01

    The current EURATOM Basic Safety Standards (BSS), the Council Directive 96/29/EURATOM of 13 May 1996 [1], contain general provisions for clearance in Article 5 but no specific clearance levels (in terms of nuclide specific mass or surface related activity values). A set of levels has been developed in IAEA Safety Guide RSG-1.7 [5] (for details on the derivation see IAEA Safety Report 44 [6]) as general clearance levels and exemption values for large quantities for inclusion in the IAEA BSS [4]. This set of values has been proposed by the European Commission (EC) as an internationally harmonised set of clearance levels that could be incorporated into the BSS. Furthermore, the EC has proposed to use this set of values also as a new set of exemption values, replacing the current set of mass related exemption values of Annex I Table A Column 3 of the BSS. It was, however, decided that the technical background and further details of the derivation of the set of values should be evaluated before actually incorporating these values into the EURATOM BSS. Therefore, a study was commissioned by the European Commission, DG TREN, and has been prepared by Brenk Systemplanung GmbH in 2008 [7]. This study provides a basis for a decision whether the levels of RS-G-1.7 could be used as clearance levels for unconditional clearance and as a replacement for mass related exemption values in the BSS. It also compares the background and approach of the relevant documents (RS-G-1.7 and SR 44 of the IAEA and RP 122 part I [2] of the European Commission) and the way in which clearance levels have been derived (analysis of scenarios, parameter values and calculation codes). The comparison is performed and evaluated on a nuclide-specific basis, and conclusions are drawn where further evaluation of the values of RS-G-1.7 would be needed. In a second part, the study evaluates and discusses implications for practices not requiring reporting or authorisation under the current exemption values

  9. Application of clearance automatic laser inspection system to clearance measurement of concrete waste

    International Nuclear Information System (INIS)

    Recently, the Clearance Automatic Laser Inspection System (CLALIS) has been developed for the clearance measurement of metal scraps. It utilizes three-dimensional (3D) laser scanning, y-ray measurement and Monte Carlo calculation, and has outstanding detection ability. For the clearance measurement of concrete segments, the effect of background (BG) gamma rays from natural radionuclides in the measurement target, such as K-40 and the radioactive decay products of Th-232 and U-238, should be compensated for to ensure adequate waste management. Since NE102A plastic scintillation detectors are used for y-ray measurement in CLALIS, it is impossible to distinguish between count rates of natural radionuclides and contaminants on the basis of gamma-ray energy information. To apply CLALIS to the clearance measurement of concrete segments, the original activity evaluation method was improved by adding a new compensation procedure. In this procedure, BG count rate due to natural radionuclides is estimated by a Monte Carlo calculation with pre-analyzed data of a representative sample of the measurement target. The activity concentration of natural radionuclides in concrete differs markedly depending on the production location of its components, such as cement and aggregates. In this study, using six mock concrete waste samples, which were composed of cement and fine aggregate from various production locations, the accuracy of BG compensation was experimentally estimated. In addition, the accuracy of calibration for concrete waste was also estimated using a number of mock concrete segments of small and large triangular prisms. By considering the uncertainties of BG compensation and calibration, the detection limit of CLALIS for concrete waste was estimated. As a result, it was revealed that CLALIS could be applied to the clearance measurement of concrete segments when the mass of the measurement target is greater than approximately 1.1 kg and the key radionuclide is Co-60

  10. Plasma HIV Viral Rebound following Protocol-Indicated Cessation of ART Commenced in Primary and Chronic HIV Infection

    DEFF Research Database (Denmark)

    Hamlyn, Elizabeth; Ewings, Fiona M; Porter, Kholoud;

    2012-01-01

    OBJECTIVES: The magnitude of HIV viral rebound following ART cessation has consequences for clinical outcome and onward transmission. We compared plasma viral load (pVL) rebound after stopping ART initiated in primary (PHI) and chronic HIV infection (CHI). DESIGN: Two populations with protocol-in...

  11. An accredited infrastructure for clearance of decommissioning waste

    International Nuclear Information System (INIS)

    The nuclear research reactors and a hot-cell facility at the Riso site in Denmark have been closed and are in the process of being decommissioned. This has prompted the development of an accredited infrastructure called the Clearance Function. This function is responsible for the activity concentration measurements of the clearance candidates and for the demonstration of compliance with the clearance levels for the released objects. The Clearance Function comprises laboratory facilities, measuring equipment, measuring procedures, waste handling software, software for clearance related calculations and trained personnel. An accreditation of the Clearance Function has been granted from the accreditation body, DANAK, according to the international standard ISO/IEC 17025:2005. DANAK is a member of ILAC, the International Laboratory Accreditation Cooperation. The Clearance Function has been accredited to measure surface-specific and mass-specific activities using surface contamination monitors and high purity germanium detectors. The germanium detectors are characterised and in each measurement they are calibrated using the ISOCS (registered) calibration software. Activity concentration measurements can be made on items as a whole (one or several combined measurements) or on samples from an item. In the latter case a statistical method is used to evaluate whether the activity concentration is above or below the clearance level. The paper describes the different elements of the Clearance Function and the processing of items through the flow routes depending on the likely activity content and the distribution of activity. It is shown how uncertainties are incorporated in the clearance criteria. Experience from the first year of operation of the Clearance Function is reported. (author)

  12. An accredited infrastructure for clearance of decommissioning waste

    International Nuclear Information System (INIS)

    The nuclear research reactors and a hot-cell facility at the Riso site in Denmark have been closed and are in the process of being decommissioned. This has prompted the development of an accredited infrastructure called the Clearance Function. This function is responsible for the activity concentration measurements of the clearance candidates and for the demonstration of compliance with the clearance levels for the released objects. The Clearance Function comprises laboratory facilities, measuring equipment, measuring procedures, waste handling software, software for clearance related calculations and trained personnel. An accreditation of the Clearance Function has been granted from the accreditation body, DANAK, according to the international standard ISO/IEC 17025:2005. DANAK is a member of ILAC, the International Laboratory Accreditation Cooperation. The Clearance Function has been accredited to measure surface-specific and mass-specific activities using surface contamination monitors and high purity germanium detectors. The germanium detectors are characterised and in each measurement they are calibrated using the ISOCS calibration software. Activity concentration measurements can be made on items as a whole (one or several combined measurements) or on samples from an item. In the latter case a statistical method is used to evaluate whether the activity concentration is above or below the clearance level. The paper describes the different elements of the Clearance Function and the processing of items through the flow routes depending on the likely activity content and the distribution of activity. It is shown how uncertainties are incorporated in the clearance criteria. Experience from the first year of operation of the Clearance Function is reported. (author)

  13. Load forecasting

    International Nuclear Information System (INIS)

    Slides used in a presentation at The Power of Change Conference in Vancouver, BC in April 1995 about the changing needs for load forecasting were presented. Technological innovations and population increase were said to be the prime driving forces behind the changing needs in load forecasting. Structural changes, market place changes, electricity supply planning changes, and changes in planning objectives were other factors discussed. It was concluded that load forecasting was a form of information gathering, that provided important market intelligence

  14. Preparation of Viral DNA from Nucleocapsids

    OpenAIRE

    Szpara, Moriah L.; Tafuri, Yolanda R.; Enquist, L W

    2011-01-01

    Viruses are obligate cellular parasites, and thus the study of their DNA requires isolating viral material away from host cell contaminants and DNA. Several downstream applications require large quantities of pure viral DNA, which is provided by this protocol. These applications include viral genome sequencing, where the removal of host DNA is crucial to optimize data output for viral sequences, and the production of new viral recombinant strains, where co-transfection of purified plasmid and...

  15. Update on Alcohol and Viral Hepatitis

    OpenAIRE

    Gitto, Stefano; Vitale, Giovanni; Villa, Erica; Andreone, Pietro

    2014-01-01

    Alcohol consumption is often associated with viral hepatitis. Although alcohol is known to worsen viral liver disease, the interactions between alcohol and viral hepatitis are not fully understood. Molecular alterations in the liver due to alcohol and viral hepatitis include effects on viral replication, increased oxidative stress, cytotoxicity, and a weakened immune response. Clinically, alcohol enhances disease progression and favors induction of primitive liver neoplasm. The use of new ant...

  16. Modeling latently infected cell activation: viral and latent reservoir persistence, and viral blips in HIV-infected patients on potent therapy.

    Directory of Open Access Journals (Sweden)

    Libin Rong

    2009-10-01

    Full Text Available Although potent combination therapy is usually able to suppress plasma viral loads in HIV-1 patients to below the detection limit of conventional clinical assays, a low level of viremia frequently can be detected in plasma by more sensitive assays. Additionally, many patients experience transient episodes of viremia above the detection limit, termed viral blips, even after being on highly suppressive therapy for many years. An obstacle to viral eradication is the persistence of a latent reservoir for HIV-1 in resting memory CD4(+ T cells. The mechanisms underlying low viral load persistence, slow decay of the latent reservoir, and intermittent viral blips are not fully characterized. The quantitative contributions of residual viral replication to viral and the latent reservoir persistence remain unclear. In this paper, we probe these issues by developing a mathematical model that considers latently infected cell activation in response to stochastic antigenic stimulation. We demonstrate that programmed expansion and contraction of latently infected cells upon immune activation can generate both low-level persistent viremia and intermittent viral blips. Also, a small fraction of activated T cells revert to latency, providing a potential to replenish the latent reservoir. By this means, occasional activation of latently infected cells can explain the variable decay characteristics of the latent reservoir observed in different clinical studies. Finally, we propose a phenomenological model that includes a logistic term representing homeostatic proliferation of latently infected cells. The model is simple but can robustly generate the multiphasic viral decline seen after initiation of therapy, as well as low-level persistent viremia and intermittent HIV-1 blips. Using these models, we provide a quantitative and integrated prospective into the long-term dynamics of HIV-1 and the latent reservoir in the setting of potent antiretroviral therapy.

  17. Coamplification of HIV-1 Proviral DNA and Viral RNA in Assays Used for Quantification of HIV-1 RNA▿

    OpenAIRE

    Wan, H; Seth, A; Rainen, L; Fernandes, H.

    2010-01-01

    Elevated HIV-1 viral load (VL) observed in specimens frozen in situ in plasma preparation tubes (PPTs) compared to EDTA plasma specimens may affect therapeutic monitoring of HIV-infected patients. The increase in viral load is cell associated and minimized when plasma from the PPT is aspirated or recentrifuged prior to freezing. This study investigates the contribution of integrated HIV-1 proviral DNA to elevated VL in the quantification of HIV-1 RNA in plasma. Fifty paired specimens collecte...

  18. 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

  19. Longitudinal serum HIV RNA quantification: correlation to viral phenotype at seroconversion and clinical outcome

    DEFF Research Database (Denmark)

    Katzenstein, T L; Pedersen, C; Nielsen, C;

    1996-01-01

    . Harbouring syncytium-inducing (SI) virus at seroconversion was associated with faster progression to AIDS than non-SI (NSI; P < 0.005). The increased in vitro replication rate of SI over NSI was not translated into significantly higher serum HIV RNA. CONCLUSION: Serum HIV RNA is high around the time of......OBJECTIVE: To investigate the longitudinal changes in serum HIV RNA, and to clarify whether the viral load early in infection has a predictive value for the clinical outcome; also, to correlate viral phenotype at seroconversion and changes in CD4 cell counts with viral burden. DESIGN: Twenty...... seroconverters with HIV isolates available at seroconversion had HIV RNA quantified by polymerase chain reaction (PCR) at seroconversion and thereafter every 6 months. Mean follow-up time was 65 months. Patients were classified according to viral phenotype at seroconversion, time to AIDS progression, serum viral...

  20. Viral metagenomics and blood safety.

    Science.gov (United States)

    Sauvage, V; Eloit, M

    2016-02-01

    The characterization of the human blood-associated viral community (also called blood virome) is essential for epidemiological surveillance and to anticipate new potential threats for blood transfusion safety. Currently, the risk of blood-borne agent transmission of well-known viruses (HBV, HCV, HIV and HTLV) can be considered as under control in high-resource countries. However, other viruses unknown or unsuspected may be transmitted to recipients by blood-derived products. This is particularly relevant considering that a significant proportion of transfused patients are immunocompromised and more frequently subjected to fatal outcomes. Several measures to prevent transfusion transmission of unknown viruses have been implemented including the exclusion of at-risk donors, leukocyte reduction of donor blood, and physicochemical treatment of the different blood components. However, up to now there is no universal method for pathogen inactivation, which would be applicable for all types of blood components and, equally effective for all viral families. In addition, among available inactivation procedures of viral genomes, some of them are recognized to be less effective on non-enveloped viruses, and inadequate to inactivate higher viral titers in plasma pools or derivatives. Given this, there is the need to implement new methodologies for the discovery of unknown viruses that may affect blood transfusion. Viral metagenomics combined with High Throughput Sequencing appears as a promising approach for the identification and global surveillance of new and/or unexpected viruses that could impair blood transfusion safety. PMID:26778104

  1. 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.

  2. 48 CFR 2452.237-75 - Clearance of contractor personnel.

    Science.gov (United States)

    2010-10-01

    ... personnel. 2452.237-75 Section 2452.237-75 Federal Acquisition Regulations System DEPARTMENT OF HOUSING AND... Clauses 2452.237-75 Clearance of contractor personnel. As prescribed in 2437.110(e), insert the following clause in solicitations and contracts. Clearance of Contractor Personnel (OCT 1999) (a) General....

  3. 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...

  4. 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...

  5. 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...

  6. 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. PMID:25683459

  7. 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. PMID:26195256

  8. 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 REGULATIONS (CONTINUED) AFFIRMATIVE EMPLOYMENT PROGRAMS Disabled Veterans Affirmative Action Program § 720.307 Interagency report clearance. The...

  9. 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 REGULATIONS NAVIGATION OF FOREIGN CIVIL AIRCRAFT WITHIN THE UNITED STATES Rules Generally Applicable § 375.24 Entry and clearance. All...

  10. 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 Section 160.115 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) PORTS AND WATERWAYS SAFETY PORTS AND WATERWAYS SAFETY-GENERAL Control of Vessel and Facility Operations § 160.115 Withholding of clearance....

  11. 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. 952.204-73 Section 952.204-73 Federal Acquisition Regulations System DEPARTMENT OF ENERGY CLAUSES AND FORMS SOLICITATION PROVISIONS AND CONTRACT CLAUSES Text of Provisions and Clauses 952.204-73 Facility clearance. As prescribed in 904.404(d)(5),...

  12. Benefits of Improved HP Turbine Active Clearance Control

    Science.gov (United States)

    Ruiz, Rafael; Albers, Bob; Sak, Wojciech; Seitzer, Ken; Steinetz, Bruce M.

    2007-01-01

    As part of the NASA Propulsion 21 program, GE Aircraft Engines was contracted to develop an improved high pressure turbine(HPT) active clearance control (ACC) system. The system is envisioned to minimize blade tip clearances to improve HPT efficiency throughout the engine operation range simultaneously reducing fuel consumption and emissions.

  13. Allometric scaling for predicting human clearance of bisphenol A

    International Nuclear Information System (INIS)

    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

  14. Radioaerosol delivery and clearance in patients with respiratory failure

    International Nuclear Information System (INIS)

    A technique for radioaerosol delivery to patients requiring mechanical ventilation is described. Ventilation images and pulmonary radioaerosol clearance rates were successfully obtained in 35 patients regardless of ventilator type or level of positive end-expiratory pressure (PEEP). Those patients with noncardiogenic pulmonary edema (NPE) had significantly increased clearance rates relative to those patients in whom NPE was not present

  15. 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.

  16. Study of global operational needs for mine clearance equipment

    Science.gov (United States)

    Blagden, Paddy M.

    2003-09-01

    The Geneva International Centre for Humanitarian Demining studied the needs of landmine clearance groups for equipment to carry out specific functions of mine clearance. This was done on a global level, and useful results were obtained, which will provide the basis for further analysis.

  17. Direct association between pharyngeal viral secretion and host cytokine response in severe pandemic influenza

    Directory of Open Access Journals (Sweden)

    Castro Carmen

    2011-08-01

    Full Text Available Abstract Background Severe disease caused by 2009 pandemic influenza A/H1N1virus is characterized by the presence of hypercytokinemia. The origin of the exacerbated cytokine response is unclear. As observed previously, uncontrolled influenza virus replication could strongly influence cytokine production. The objective of the present study was to evaluate the relationship between host cytokine responses and viral levels in pandemic influenza critically ill patients. Methods Twenty three patients admitted to the ICU with primary viral pneumonia were included in this study. A quantitative PCR based method targeting the M1 influenza gene was developed to quantify pharyngeal viral load. In addition, by using a multiplex based assay, we systematically evaluated host cytokine responses to the viral infection at admission to the ICU. Correlation studies between cytokine levels and viral load were done by calculating the Spearman correlation coefficient. Results Fifteen patients needed of intubation and ventilation, while eight did not need of mechanical ventilation during ICU hospitalization. Viral load in pharyngeal swabs was 300 fold higher in the group of patients with the worst respiratory condition at admission to the ICU. Pharyngeal viral load directly correlated with plasma levels of the pro-inflammatory cytokines IL-6, IL-12p70, IFN-γ, the chemotactic factors MIP-1β, GM-CSF, the angiogenic mediator VEGF and also of the immuno-modulatory cytokine IL-1ra (p Conclusions Severe respiratory disease caused by the 2009 pandemic influenza virus is characterized by the existence of a direct association between viral replication and host cytokine response, revealing a potential pathogenic link with the severe disease caused by other influenza subtypes such as H5N1.

  18. Comparative genotypic study of viral RNA and proviral DNA in HIV-1 patients

    OpenAIRE

    Chan, Wing-tsin, Alison; 陳穎芊

    2015-01-01

    Highly Active Antiretroviral Therapy (HAART) has been used for HIV-1 treatment for more than a decade. Prior identification of drug resistance associated mutations and viral tropism provides valuable information for physicians in optimizing the best HAART regimens for each patient. Plasma RNA has long been used as the major laboratory marker as it reflects the status of circulating virus. However, it might not be as informative in patients with low viral loads. Proviral DNA was therefore sugg...

  19. Guidance of clearance related standards in reactor facilities

    International Nuclear Information System (INIS)

    The reactor regulation law was amended in May 2005 to provide for the clearance system. The regulatory body confirmed radioactivity concentration of material and allowed the material be classified as 'material cleared from regulatory control'. The procedure of confirmation consisted of two steps; 1) methodology and 2) results, of measurement and assessment. Clearance related standards were issued as ordinance of Ministry and NISA information notice, which specified radioactive nuclides, radioactivity concentration, evaluation unit, how to decide radioactivity concentration, radiation measurement equipment and control of object material. This report was guidance of clearance related standards in reactor facilities with explanatory notes. By applying the clearance system, material of insignificant radiation level, which was part of concrete or metals generated from decommissioning of reactor facilities, could be released from regulatory control of radioactive waste as clearance material, and recycle of such material could result in reduction of radioactive waste amount. (T. Tanaka)

  20. Integrin Activation and Viral Infection

    Institute of Scientific and Technical Information of China (English)

    Shan-dian GAO; Jun-zheng DU; Jian-hua ZHOU; Hui-yun CHANG; Qing-ge XIE

    2008-01-01

    Integrins are members of a ubiquitous membrane receptor family which includes 18 different α subunits and 8 β subunits forming more than 20 α/β heterodimers. Integrins play key functions in vascular endothelial cell and tumour cell adhesion, lymphocyte trafficking, tumor growth and viral infection. Current understanding of the molecular basis of integrins as viral receptors has been achieved through many decades of study into the biology of transmembrane glycoproteins and their interactions with several viruses. This review provides a summary of the current knowledge on the molecular bases of interactions between viruses and integrins, which are of potential practical significance. Inhibition of virus-integrin interactions at the points of virus attachment or entry will provide a novel approach for the therapeutic treatment of viral diseases.

  1. Calculation of the renal clearance by dynamic measurement of the excreted activity

    International Nuclear Information System (INIS)

    Aim: In this paper we present a new method to measure the renal slope-clearance of Tc-99m-MAG-3 in a single-shot model (Excretion-clearance). Method: A renal scintigraphy with Tc-99m-MAG-3 was performed in 22 patients. The excreted activity of the tracer in the kidneys and the bladder was dynamically measured using a double-head gamma-camera. Additionally, the total absorption over the kidneys and the bladder was determined. The Excretion-clearance was calculated in a differential and an integral variant. Simultaneously the 2-compartment-clearance (Sapirstein-clearance), the Oberhausen-clearance and the Bubeck-clearance were calculated. Results: The Sapirstein-clearance is considered as the 'goldstandard' in a single-shot modell. The correlation of the Bubeck-clearance and the Oberhausen-clearance ranged from r=0.96 to r=0.97, the Excretion-clearance (differential-method) correlated with r=0.90. The absolute difference of the clearance-values was lowest comparing the Bubeck-clearance with the Sapirstein-clearance with an average difference of 11%, whereas the Excretion-clearance revealed at least an average difference of 21% and the Oberhausen-clearance of 24%. Discussion: The Excretion-clearance requires a more complicated protocoll measuring the clearance in comparison to the Bubeck-clearance. The results of the excretion-clearance differ more from the Sapirstein-clearance with regard to the examined patient population than the Bubeck-clearance. Regarding the theoretical basis of the methods, we expect advantages of the Excretion-clearance compared with the Bubeck-clearance in patients with compartmental disproportion or with a low clearance. We are going to prove this in combination with the above mentioned methodical improvements in a further study. (orig.)

  2. Attenuated viral hepatitis in Trem1-/- mice is associated with reduced inflammatory activity of neutrophils.

    Science.gov (United States)

    Kozik, Jan-Hendrik; Trautmann, Tanja; Carambia, Antonella; Preti, Max; Lütgehetmann, Marc; Krech, Till; Wiegard, Christiane; Heeren, Joerg; Herkel, Johannes

    2016-01-01

    TREM1 (Triggering Receptor Expressed on Myeloid Cells 1) is a pro-inflammatory receptor expressed by phagocytes, which can also be released as a soluble molecule (sTREM1). The roles of TREM1 and sTREM1 in liver infection and inflammation are not clear. Here we show that patients with hepatitis B virus (HBV) or hepatitis C virus (HCV) infection manifest elevated serum levels of sTREM1. In mice, experimental viral hepatitis induced by infection with Lymphocytic Choriomeningitis Virus (LCMV)-WE was likewise associated with increased sTREM1 in serum and urine, and with increased TREM1 and its associated adapter molecule DAP12 in the liver. Trem1-/- mice showed accelerated clearance of LCMV-WE and manifested attenuated liver inflammation and injury. TREM1 expression in the liver of wild-type mice was mostly confined to infiltrating neutrophils, which responded to LCMV by secretion of CCL2 and TNF-α, and release of sTREM1. Accordingly, the production of CCL2 and TNF-α was decreased in the livers of LCMV-infected Trem1-/- mice, as compared to LCMV-infected wildtype mice. These findings indicate that TREM1 plays a role in viral hepatitis, in which it seems to aggravate the immunopathology associated with viral clearance, mainly by increasing the inflammatory activity of neutrophils. PMID:27328755

  3. Analysis of conservativity analysis for clearance levels. Final report

    International Nuclear Information System (INIS)

    When deriving clearance levels for material from nuclear installations it is necessary to proceed with a certain degree of conservativity. This can, however, differ between various sets of clearance levels leading to inconsistencies between clearance pathways. The aim of the work therefore is to compare levels of conservativity for the following two sets of clearance levels: clearance levels for disposal as conventional waste and for metallic materials for recycling/reuse. A method was developed to quantify the degree of conservativity and make it comparable. The actual and future situation for disposal of (conventional) wastes in Germany was analysed. In addition, the masses, nuclide vectors, geographical distribution etc. for slightly radioactive material being cleared for conventional disposal was analysed and modelled and the resulting dose distributions were calculated. The values for the clearance levels were taken from the 1995 recommendation by the German Commission on Radiation Protection (SSK). By using realistic scenarios, the exposure was calculated for the personnel on the landfills and for persons of the general public being exposed via groundwater pathways. It could be shown that the trivial dose range will not be exceeded even if the masses of cleared material per landfill site exceed 100 Mg/a. Because of the types and distribution of nuclear installations in Germany and because of the nuclide vectors it is therefore not necessary to limit the masses per landfill sites. Clearance levels that are determined by the exposure pathways external exposure to and the inhalation of dust by the landfill personnel show a similar level of conservativity as those for metal scrap. This means that the clearance levels for gamma emitting nuclides are not overly restrictive. Although radiologically justified, raising the clearance levels would not lead to an increase of the material quantities because other nuclides of the respective nuclide vectors are limiting. In

  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. T Cell Memory in the Context of Persistent Herpes Viral Infections

    Directory of Open Access Journals (Sweden)

    Nicole Torti

    2012-07-01

    Full Text Available The generation of a functional memory T cell pool upon primary encounter with an infectious pathogen is, in combination with humoral immunity, an essential process to confer protective immunity against reencounters with the same pathogen. A prerequisite for the generation and maintenance of long-lived memory T cells is the clearance of antigen after infection, which is fulfilled upon resolution of acute viral infections. Memory T cells play also a fundamental role during persistent viral infections by contributing to relative control and immuosurveillance of active replication or viral reactivation, respectively. However, the dynamics, the phenotype, the mechanisms of maintenance and the functionality of memory T cells which develop upon acute/resolved infection as opposed to chronic/latent infection differ substantially. In this review we summarize current knowledge about memory CD8 T cell responses elicited during α-, β-, and γ-herpes viral infections with major emphasis on the induction, maintenance and function of virus-specific memory CD8 T cells during viral latency and we discuss how the peculiar features of these memory CD8 T cell responses are related to the biology of these persistently infecting viruses.

  6. 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

  7. Inflammatory monocytes and the pathogenesis of viral encephalitis

    Directory of Open Access Journals (Sweden)

    Terry Rachael L

    2012-12-01

    Full Text Available Abstract Monocytes are a heterogeneous population of bone marrow-derived cells that are recruited to sites of infection and inflammation in many models of human diseases, including those of the central nervous system (CNS. Ly6Chi/CCR2hi inflammatory monocytes have been identified as the circulating precursors of brain macrophages, dendritic cells and arguably microglia in experimental autoimmune encephalomyelitis; Alzheimer’s disease; stroke; and more recently in CNS infection caused by Herpes simplex virus, murine hepatitis virus, Theiler’s murine encephalomyelitis virus, Japanese encephalitis virus and West Nile virus. The precise differentiation pathways and functions of inflammatory monocyte-derived populations in the inflamed CNS remains a contentious issue, especially in regard to the existence of monocyte-derived microglia. Furthermore, the contributions of monocyte-derived subsets to viral clearance and immunopathology are not well-defined. Thus, understanding the pathways through which inflammatory monocytes migrate to the brain and their functional capacity within the CNS is critical to inform future therapeutic strategies. This review discusses some of the key aspects of inflammatory monocyte trafficking to the brain and addresses the role of these cells in viral encephalitis.

  8. Overview of hepatitis B viral replication and genetic variability.

    Science.gov (United States)

    Tong, Shuping; Revill, Peter

    2016-04-01

    Chronic infection with hepatitis B virus (HBV) greatly increases the risk for liver cirrhosis and hepatocellular carcinoma (HCC). HBV isolates worldwide can be divided into ten genotypes. Moreover, the immune clearance phase selects for mutations in different parts of the viral genome. The outcome of HBV infection is shaped by the complex interplay of the mode of transmission, host genetic factors, viral genotype and adaptive mutations, as well as environmental factors. Core promoter mutations and mutations abolishing hepatitis B e antigen (HBeAg) expression have been implicated in acute liver failure, while genotypes B, C, subgenotype A1, core promoter mutations, preS deletions, C-terminal truncation of envelope proteins, and spliced pregenomic RNA are associated with HCC development. Our efforts to treat and prevent HBV infection are hampered by the emergence of drug resistant mutants and vaccine escape mutants. This paper provides an overview of the HBV life cycle, followed by review of HBV genotypes and mutants in terms of their biological properties and clinical significance. PMID:27084035

  9. TDP-43 regulates endogenous retrovirus-K viral protein accumulation.

    Science.gov (United States)

    Manghera, Mamneet; Ferguson-Parry, Jennifer; Douville, Renée N

    2016-10-01

    The concomitant expression of neuronal TAR DNA binding protein 43 (TDP-43) and human endogenous retrovirus-K (ERVK) is a hallmark of ALS. Since the involvement of TDP-43 in retrovirus replication remains controversial, we sought to evaluate whether TDP-43 exerts an effect on ERVK expression. In this study, TDP-43 bound the ERVK promoter in the context of inflammation or proteasome inhibition, with no effect on ERVK transcription. However, over-expression of ALS-associated aggregating forms of TDP-43, but not wild-type TDP-43, significantly enhanced ERVK viral protein accumulation. Human astrocytes and neurons further demonstrated cell-type specific differences in their ability to express and clear ERVK proteins during inflammation and proteasome inhibition. Astrocytes, but not neurons, were able to clear excess ERVK proteins through stress granule formation and autophagy. In vitro findings were validated in autopsy motor cortex tissue from patients with ALS and neuro-normal controls. We further confirmed marked enhancement of ERVK in cortical neurons of patients with ALS. Despite evidence of enhanced stress granule and autophagic response in ALS cortical neurons, these cells failed to clear excess ERVK protein accumulation. This highlights how multiple cellular pathways, in conjunction with disease-associated mutations, can converge to modulate the expression and clearance of viral gene products from genomic elements such as ERVK. In ALS, ERVK protein aggregation is a novel aspect of TDP-43 misregulation contributing towards the pathology of this neurodegenerative disease. PMID:27370226

  10. 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.

  11. 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 carcinoma,HCC)、对照组.HCC组及对照组均明显低于其他3组(P<0.01),其余各组间两两比较,差异有统计学意义(P<0.05).CD3+、CD4+T淋巴细胞在AHB组最高,对照组次之,LC组最低;AHB组、对照组及CHB组均明显高于LC组(P< 0.05);AHB组、对照组明显高于HCC组(P<0.05).CD8+T淋巴细胞在对照组最高,AHB组次之,LC组最低;但仅AHB组、对照组明显高于LC组(P<0.05).AHB组CD4+/CD8+明显高于其他组(P<0.01).CHB及LC组病毒载量最高,均明显高于HCC及AHB组(P<0.05).CD3+、CD4+、CD8+T淋巴细胞与病毒载量、IDO蛋白及IDO活性均呈负相关,CD8+T淋巴细胞与IDO mRNA呈负相关(r=-0.287,P=0.039);CD4+/CD8+与IDO蛋白及IDO活性均呈正相关(r=0.470,P=0.000;r=0.285,P=0.040),病毒载量与IDO mRNA、IDO蛋白及IDO活性均呈正相关(r=0.530,P=0.001;r=0.416,P=0.002;r=0.649,P=0.000).结论 HBV感染者IDO表达明显增强,与病毒载量呈正相关,与T淋巴细胞呈负相关,其早期升高有利于病毒清除,但持续升高会导致HBV特异性T淋巴细胞功能抑制,使HBV慢性化.%Objective To investigate the expression levels of indoleamine 2,3-dioxygenase(IDO) and the correlation between IDO level, T cell subsets and viral load in hepatitis B related liver disease subjects. Methods Peripheral blood samples were collected, and the the expression level of IDO Mrna and IDO protein in PBMC

  12. Nuclear regulation. NRC's security clearance program can be strengthened

    International Nuclear Information System (INIS)

    Because of the national security implications of its programs, the Nuclear Regulatory Commission (NRC) investigates the background of its employees and consultants as well as others to ensure that they are reliable and trustworthy. If the investigation indicates that an employee will not endanger national security, NRC grants a security clearance that allows access to classified information, material, and facilities. NRC also requires periodic checks for some clearance holders to ensure their continued clearance eligibility. The Chairman, Subcommittee on Environment, Energy, and Natural Resources, House Committee on Government Operations, asked GAO to review NRC's personnel security clearance program and assess the procedures that NRC uses to ensure that those who operate nuclear power plants do not pose a threat to the public. The Atomic Energy Act of 1954 requires NRC to conduct background investigations of its employees and consultants as well as others who have access to classified information, material, or facilities. To do this, NRC established a personnel security clearance program. Under NRC policies, a security clearance is granted after the Office of Personnel Management (OPM) or the Federal Bureau of Investigation checks the background of those applying for an NRC clearance. NRC also periodically reassesses the integrity of those holding the highest level clearance. NRC employees, consultants, contractors, and licensees as well as other federal employees hold approximately 10,600 NRC clearances. NRC does not grant clearances to commercial nuclear utility employees unless they require access to classified information or special nuclear material. However, the utilities have voluntarily established screening programs to ensure that their employees do not pose a threat to nuclear plants. NRC faces a dilemma when it hires new employees. Although its policy calls for new hires to be cleared before they start work, the security clearance process takes so long

  13. A highly intensified ART regimen induces long-term viral suppression and restriction of the viral reservoir in a simian AIDS model.

    Directory of Open Access Journals (Sweden)

    Iart Luca Shytaj

    Full Text Available Stably suppressed viremia during ART is essential for establishing reliable simian models for HIV/AIDS. We tested the efficacy of a multidrug ART (highly intensified ART in a wide range of viremic conditions (10³-10⁷ viral RNA copies/mL in SIVmac251-infected rhesus macaques, and its impact on the viral reservoir. Eleven macaques in the pre-AIDS stage of the disease were treated with a multidrug combination (highly intensified ART consisting of two nucleosidic/nucleotidic reverse transcriptase inhibitors (emtricitabine and tenofovir, an integrase inhibitor (raltegravir, a protease inhibitor (ritonavir-boosted darunavir and the CCR5 blocker maraviroc. All animals stably displayed viral loads below the limit of detection of the assay (i.e. <40 RNA copies/mL after starting highly intensified ART. By increasing the sensitivity of the assay to 3 RNA copies/mL, viral load was still below the limit of detection in all subjects tested. Importantly, viral DNA resulted below the assay detection limit (<2 copies of DNA/5*10⁵ cells in PBMCs and rectal biopsies of all animals at the end of the follow-up, and in lymph node biopsies from the majority of the study subjects. Moreover, highly intensified ART decreased central/transitional memory, effector memory and activated (HLA-DR⁺ effector memory CD4⁺ T-cells in vivo, in line with the role of these subsets as the main cell subpopulations harbouring the virus. Finally, treatment with highly intensified ART at viral load rebound following suspension of a previous anti-reservoir therapy eventually improved the spontaneous containment of viral load following suspension of the second therapeutic cycle, thus leading to a persistent suppression of viremia in the absence of ART. In conclusion, we show, for the first time, complete suppression of viral load by highly intensified ART and a likely associated restriction of the viral reservoir in the macaque AIDS model, making it a useful platform for testing

  14. A mouse model for studying the clearance of hepatitis B virus in vivo using a luciferase reporter.

    Directory of Open Access Journals (Sweden)

    Sheng-qiang Liang

    Full Text Available Hepatitis B virus(HBV infection remains a global problem, despite the effectiveness of the Hepatitis B vaccine in preventing infection. The resolution of Hepatitis B virus infection has been believed to be attributable to virus-specific immunity. In vivo direct evaluation of anti-HBV immunity in the liver is currently not possible. We have developed a new assay system that detects HBV clearance in the liver after the hydrodynamic transfer of a reporter gene and over-length, linear HBV DNA into hepatocytes, followed by bioluminescence imaging of the reporter gene (Fluc. We employed bioluminescence detection of luciferase expression in HBV-infected hepatocytes to measure the Hepatitis B core antigen (HBcAg-specific immune responses directed against these infected hepatocytes. Only HBcAg-immunized, but not mock-treated, animals decreased the amounts of luciferase expression, HBsAg and viral DNA from the liver at day 28 after hydrodynamic infection with over-length HBV DNA, indicating that control of luciferase expression correlates with viral clearance from infected hepatocytes.

  15. Impact of Load Behavior on Transient Stability and Power Transfer Limitations

    OpenAIRE

    Gordon, Mark

    2009-01-01

    This paper presents utility based load modeling practices and explores the interaction between loads and the power system and the effect of the interaction on transient stability and power transfer limitations. The effect of load composition is investigated at major load centers together with the impact on rotor angle excursions of large scale generators during the transient and post-transient period. Responses of multi-induction motor stalling are also considered for different fault clearanc...

  16. Air pollution particles diminish bacterial clearance in the primed lungs of mice

    International Nuclear Information System (INIS)

    Epidemiological studies reveal increased incidence of lung infection when air pollution particle levels are increased. We postulate that one risk factor for bacterial pneumonia, prior viral infection, can prime the lung for greater deleterious effects of particles via the interferon-gamma (IFN-γ) characteristic of successful host anti-viral responses. To test this postulate, we developed a mouse model in which mice were treated with γ-interferon aerosol, followed by exposure to concentrated ambient particles (CAPs) collected from urban air. The mice were then infected with Streptococcus pneumoniae and the effect of these treatments on the lung's innate immune response was evaluated. The combination of IFN-γ priming and CAPs exposure enhanced lung inflammation, manifest as increased polymorphonuclear granulocyte (PMN) recruitment to the lung, and elevated expression of pro-inflammatory cytokine mRNAs. Combined priming and CAPs exposure resulted in impaired pulmonary bacterial clearance, as well as increased oxidant production and diminished bacterial uptake by alveolar macrophages (AMs) and PMNs. The data suggest that priming and CAPs exposure lead to an inflamed alveolar milieu where oxidant stress causes loss of antibacterial functions in AMs and recruited PMNs. The model reported here will allow further analysis of priming and CAPs exposure on lung sensitivity to infection

  17. Recycling Endosomes and Viral Infection.

    Science.gov (United States)

    Vale-Costa, Sílvia; Amorim, Maria João

    2016-01-01

    Many viruses exploit specific arms of the endomembrane system. The unique composition of each arm prompts the development of remarkably specific interactions between viruses and sub-organelles. This review focuses on the viral-host interactions occurring on the endocytic recycling compartment (ERC), and mediated by its regulatory Ras-related in brain (Rab) GTPase Rab11. This protein regulates trafficking from the ERC and the trans-Golgi network to the plasma membrane. Such transport comprises intricate networks of proteins/lipids operating sequentially from the membrane of origin up to the cell surface. Rab11 is also emerging as a critical factor in an increasing number of infections by major animal viruses, including pathogens that provoke human disease. Understanding the interplay between the ERC and viruses is a milestone in human health. Rab11 has been associated with several steps of the viral lifecycles by unclear processes that use sophisticated diversified host machinery. For this reason, we first explore the state-of-the-art on processes regulating membrane composition and trafficking. Subsequently, this review outlines viral interactions with the ERC, highlighting current knowledge on viral-host binding partners. Finally, using examples from the few mechanistic studies available we emphasize how ERC functions are adjusted during infection to remodel cytoskeleton dynamics, innate immunity and membrane composition. PMID:27005655

  18. Viral hepatitis and hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Two papers in this volume are in INIS scope, respectively dealing with MRI in the study of viral hepatitis and hepatocellular carcinoma, and The use of 131I-labeled Lipidol in the diagnosis of hepato-cellular carcinoma. (H.W.). refs.; figs.; tabs

  19. Comparative evaluation of iohexol and inulin clearance for glomerular filtration rate determinations

    International Nuclear Information System (INIS)

    The authors have evaluated iohexol as a filtration marker in 150 children. The clearance of iohexol was compared with that of inulin or with a formula clearance. The single-sample clearance of iohexol showed a good correlation with the clearance of inulin. The clearance of iohexol correlated well with the formula clearance. The optimal blood sampling time for iohexol clearance determinations appears to be between 120 and 180 min after injection, at least in patient with relatively normal filtration rates. It is concluded that iohexol clearance is an accurate method of determining the glomerular filtration rate in clinical practice. 25 refs., 5 figs

  20. Measurement of tracheobronchial clearance after sauna in subjects with chronic bronchitis.

    OpenAIRE

    van Hengstum, M; Festen, J.; Corstens, F.

    1991-01-01

    The effect of sauna on tracheobronchial clearance was studied in five male patients with chronic bronchitis by a radioaerosol technique. No enhancement of tracheobronchial clearance could be detected.