Spelling suggestions: "subject:"antiretroviral""
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Genetic Engineering of T Lymphocytes for Cancer Immunotherapy : Optimisation of Gene TransferLindqvist, Camilla January 2006 (has links)
T lymphocytes can be rendered specific against a wide range of antigens by the genetic transfer of a chimeric receptor, a fusion between the antigen-binding domain of an antibody and the signalling domain of a T cell receptor. The use of such chimeric T lymphocytes has shown promising results for cancer therapy. Previous experiments in our laboratory have shown low rates of gene transfer using retroviral vectors. In this study, investigations have been done to increase the number of genetically modified cells. Different enhancers such as PLL and polybrene have previously been used in combination with retroviral transduction. The optimal retroviral protocol in this study showed to be the use of retrovectors produced with twice the normal concentration of the plasmids encoding env and gag-pol rather than the use of the enhancers. A 6-day pre stimulation of T lymphocytes prior transduction together with a centrifugation step increased the rate of modified cells even further. Alternative approaches of gene transfer were also investigated, including plasmid transfection and adenoviral transduction. While transfection protocols yielded low numbers of modified cells, adenoviral vectors showed the highest rate of gene transfer. / Cancer är den sjukdom som idag, efter hjärt-kärl-sjukdomar, kräver flest dödsfall i i-länder. Som en alternativ behandlingsmetod mot cancer pågår just nu forskning om genetiskt förbättrade immunceller, s.k. chimära T lymfocyter, skulle kunna användas för att döda tumörceller. De chimära cellerna är utrustade med en konstgjord receptor som är en fusion av en antikropp och en signalkedja. Det gör att cellerna kan riktas mot ett brett urval av cancertyper. Att få cellerna att ta upp generna som behövs för den konstgjorda receptorn har visats sig vara problematiskt. Den här studien har därför som mål att förbättra cellernas förmåga att ta upp gener. För detta har vi använt oss av retrovirus- och adenovirus-system tillsammans med försök att få cellerna att spontant ta upp generna, sk. plasmid-transfektion. Studien har visat att de båda virussystemen ger högst antal modifierade celler. Olika substanser som tidigare har visat sig förhöja graden av gentillförsel har testats, men vår studie har visat att tillverkningen av virusvektorerna har större påverkan på resultaten än någon av de olika hjälpmedlen.
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Desenvolvimento da linhagem celular LEY79SF para produção de adenovírus livre de partículas competentes de replicação / Development LEY79SF line for production of RCA-free AdDuarte, Patrícia 05 October 2009 (has links)
A presença de Ad com competência para replicar (RCA, replication-competent adenovirus) nas preparações é um dos maiores problemas para a produção de Ad em larga escala. RCAs são gerados pela recombinação entre seqüência do vetor e seqüência homóloga do gene E1 presente nas células helper. Objetivo: desenvolver uma nova linhagem auxiliar para produção de Ad livre de RCA - LEY79 - derivada da linhagem de retinoblastoma humano Y79, tratando-se da primeira linhagem empacotadora de adenovírus com inativação mutacional da proteína supressora de tumor pRb, que crescem em suspensão. Células Y79 foram infectadas com o retrovírus pCLDE1A/E1BSN, selecionadas com G418. A eficiência de produção de AdeGFP na linhagem LEY79 foi testada e comparada com a HEK293A. Células Y79 foram adaptadas em meio livre de soro. Esperamos com a linhagem LEY79SF inovar no campo de processos para a produção de Ad recombinante. / The presence of Ad with the ability to replicate (RCA, replication-competent adenovirus) in preparations is a major problem in the large-scale production of Ad. RCAs are generated by recombination between the vector sequence and sequence of the homologous gene in E1 helper cells. Objective: To develop a new helper cell line for the production of RCA-free Ad., called LEY79, derived from the Y79 of human retinoblastoma line, the first line Packer adenovirus with mutational inactivation of the tumor suppressor protein pRb, which are adapted to grow in suspension. Y79 cells were infected with the retrovirus pCLDE1A/E1BSN, selected with G418. The efficiency of production of AdeGFP in the LEY79 was tested and compared with the HEK293A. Y79 cells were adapted to grow in serum-free medium. We hope that use of the the LEY79SF cell line will promote innovation in the processing and production of recombinant Ad.
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Assessment of health-related quality of life of adult highly active anti-retroviral therapy recipients at the Kagera Regional Hospital Tanzania.Magafu, Mgaywa. January 2009 (has links)
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<p style="margin-bottom: 0.0001pt / line-height: normal / " class="MsoNormal"><span style="font-size: 10pt / font-family: " / Times New Roman" / ," / serif" / ">Background: The care and treatment for people with HIV/AIDS (PLWHA) at the Kagera regional hospital began in February 2005. It is important to evaluate quality of life (QOL) of highly active anti-retroviral therapy (HAART) recipients periodical to assess HAART&rsquo / s effectiveness. This study aimed to assess the health-related QOL (HRQOL) of HAART recipients and determine factors associated with it, two years after the programme had started at the kagera regional hospital in Tanzania. Results: The HRQOL of HAART recipients was generally lower than that of the general population. However, the general health perceptions (p=0.191) and mental health (p=0.161) means score of HAART recipients were not different from those of the Tanzanian general population. About 89% of the HAART recipients reported better health than in the previous years. Chronic diseases were associated with lower HRQOL of HAART recipients independently of other factors. HAART recipients with chronic diseases co-morbidity were more likely to score below the general population&rsquo / s mean score for mental health (p=0.007). While the effect of chronic diseases on HRQOL among those who recorded CD4+ cell increase was negative (OR=13.6,95%CI=3.7 / 49.9), there was no effect on those who did not have such an increase. Adherence to ARVs and CD4+ cell count were not associated with HRQOL.   /   /   /   /   /   / <span style=""> <o:p></o:p></span></span></p>
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<span style="font-size: 12pt / font-family: " / Times New Roman" / ," / serif" / "><span style="">  / </span><span style="">  / </span><span style="">  / </span><span style="">  / </span><span style=""> </span><o:p></o:p></span></p>
<p>  / </p>
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Assessment of health-related quality of life of adult highly active anti-retroviral therapy recipients at the Kagera Regional Hospital Tanzania.Magafu, Mgaywa. January 2009 (has links)
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<p style="margin-bottom: 0.0001pt / line-height: normal / " class="MsoNormal"><span style="font-size: 10pt / font-family: " / Times New Roman" / ," / serif" / ">Background: The care and treatment for people with HIV/AIDS (PLWHA) at the Kagera regional hospital began in February 2005. It is important to evaluate quality of life (QOL) of highly active anti-retroviral therapy (HAART) recipients periodical to assess HAART&rsquo / s effectiveness. This study aimed to assess the health-related QOL (HRQOL) of HAART recipients and determine factors associated with it, two years after the programme had started at the kagera regional hospital in Tanzania. Results: The HRQOL of HAART recipients was generally lower than that of the general population. However, the general health perceptions (p=0.191) and mental health (p=0.161) means score of HAART recipients were not different from those of the Tanzanian general population. About 89% of the HAART recipients reported better health than in the previous years. Chronic diseases were associated with lower HRQOL of HAART recipients independently of other factors. HAART recipients with chronic diseases co-morbidity were more likely to score below the general population&rsquo / s mean score for mental health (p=0.007). While the effect of chronic diseases on HRQOL among those who recorded CD4+ cell increase was negative (OR=13.6,95%CI=3.7 / 49.9), there was no effect on those who did not have such an increase. Adherence to ARVs and CD4+ cell count were not associated with HRQOL.   /   /   /   /   /   / <span style=""> <o:p></o:p></span></span></p>
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<span style="font-size: 12pt / font-family: " / Times New Roman" / ," / serif" / "><span style="">  / </span><span style="">  / </span><span style="">  / </span><span style="">  / </span><span style=""> </span><o:p></o:p></span></p>
<p>  / </p>
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Liquid-liquid interface ion-transfer amperometric sensors for tenofovir as a model nucleoside/nucleotide anti-retroviral drugHamid, Sara Hamid Ibrahim January 2014 (has links)
>Magister Scientiae - MSc / Amperometric sensors for Tenofovir, a model nucleotide/ nucleoside reverse transcriptase inhibitor ARV drug, were studied based on the principle of ion-transfer electrochemistry at the membrane-stabilized oil/ water interface (O||W) in a four-electrode cell set-up. Solutions of the hydrophobic salts tetradodecylammonium tetrakis(4-chlorophenyl) borate (ETH500), ethyl violet tetraphenylborate (EthVTPB), tetrabutylammonium tetraphenylborate (TBATPB), tetraphenylphosphnium tetraphenylborate (TPphTPB) and three ionic liquids
(Methyltrioctylammonium bis(trifluoromethyl sulfonyl)imide (IL1), 1-butyl-3-
methylimdazolium bis(trifluoromethyl sulfonyl)imide (IL3) and 1-propyl-3- methylimdazolium bis(trifluoromethylsulfonyl)imide (IL4)) in nitrobenzene (NB), 1,2-
dichloroethane (DCE), and 2-nitrophenyloctyl ether (NPOE) were each tested as O-phases. The cyclic voltammograms of the resulting O||W interfaces in aq. Li2SO4 or aq. MgSO4 were compared with respect to noise, potential window, and other parameters. The three ILs were also tested as self-sufficient salts without a solvent medium. In the end, the ETH500/ DCE salt/ solvent pair was found to yield the best behaved polarizable O||W interface in aq. MgSO4. The analytical characteristics of the resulting sensors to tenofovir without (Ag|ETH500/DCE||) and with the dibenzo-18-crown-6 (Ag|ETH5000/DB18C6/DCE|| in the O-phase were studied with respect to the two pairs of peaks in the CV, namely the WO ion transfer peak and the reverse OW peak. Both sensors exhibited operational stability of 90 min. After consideration of reasonable S/N ratio and sample throughput rates, the scan rate of
25 mV/ s was used in subsequent signal interrogation with CV. The final potential windows were 0.95 V wide for Ag|ETH500 (10 mM)/ DCE|| in aq. MgSO4 (50 mM) and 0.70 V wide for Ag|ETH500 (10 mM)/ DB18C6 (50 mM)/ DCE|| in aq. MgSO4 (50 mM). From plots of peak currents versus square of scan rate, tenofovir diffusion coefficients of about 2.48 × 10-11 cm2/ s were estimated, which indicated diffusion through the supporting membrane as the rate limiting process. Based on WO ion transfer peaks, the first one exhibited a detection limit of about 5 M, a linear range of 15 – 100 M, and sensitivity of 7.09 nA M-1 towards tenofovir, whereas for the second one these were respectively 3 M, 6.32 nA M-1, and 9 –
100 M. In this way, a four-electrode amperometric detection of ion transfer process at liquid | liquid interface, both under simple and ionophore-facilitated mode, has been demonstrated as promising for analysis of tenofovir as a representative of the nucleotide/ nucleoside reverse transcriptase inhibitor ARV drugs
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Desenvolvimento da linhagem celular LEY79SF para produção de adenovírus livre de partículas competentes de replicação / Development LEY79SF line for production of RCA-free AdPatrícia Duarte 05 October 2009 (has links)
A presença de Ad com competência para replicar (RCA, replication-competent adenovirus) nas preparações é um dos maiores problemas para a produção de Ad em larga escala. RCAs são gerados pela recombinação entre seqüência do vetor e seqüência homóloga do gene E1 presente nas células helper. Objetivo: desenvolver uma nova linhagem auxiliar para produção de Ad livre de RCA - LEY79 - derivada da linhagem de retinoblastoma humano Y79, tratando-se da primeira linhagem empacotadora de adenovírus com inativação mutacional da proteína supressora de tumor pRb, que crescem em suspensão. Células Y79 foram infectadas com o retrovírus pCLDE1A/E1BSN, selecionadas com G418. A eficiência de produção de AdeGFP na linhagem LEY79 foi testada e comparada com a HEK293A. Células Y79 foram adaptadas em meio livre de soro. Esperamos com a linhagem LEY79SF inovar no campo de processos para a produção de Ad recombinante. / The presence of Ad with the ability to replicate (RCA, replication-competent adenovirus) in preparations is a major problem in the large-scale production of Ad. RCAs are generated by recombination between the vector sequence and sequence of the homologous gene in E1 helper cells. Objective: To develop a new helper cell line for the production of RCA-free Ad., called LEY79, derived from the Y79 of human retinoblastoma line, the first line Packer adenovirus with mutational inactivation of the tumor suppressor protein pRb, which are adapted to grow in suspension. Y79 cells were infected with the retrovirus pCLDE1A/E1BSN, selected with G418. The efficiency of production of AdeGFP in the LEY79 was tested and compared with the HEK293A. Y79 cells were adapted to grow in serum-free medium. We hope that use of the the LEY79SF cell line will promote innovation in the processing and production of recombinant Ad.
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Cocktails and Compliance: An Exploration of Provider Discourse Regarding Adherence to ART MedicationNarahari, Swathi, Ms. 01 January 2015 (has links)
HIV is one of the world’s most potent killers. It’s a name we have most likely heard of before, and yet there are aspects of this disease that do not get as much of the spotlight. One such aspect of HIV is adherence. Adherence is a colossal issue when dealing with anti-retroviral (ART) medications. A lack of adherence to ART dosage can lead to viral immunity and even AIDS if not treated. Despite many attempts from providers to solve the issue of adherence, studies tell us that the challenges of adherence lie within deep-seeded sociocultural and economic backgrounds. As a result, an anthropological approach seems necessary in order to grasp these challenges. Overall, I believe that adherence is learned and innate. I aim to prove this by exploring the various provider discourses regarding HIV adherence by delving into the history of AIDS, the patient/provider hierarchy, and media representations of HIV.
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Developing a Single-Cycle Infectious System to Study an ERV-K Retroviral EnvelopeAkleh, Rana Elias January 2017 (has links)
Thesis advisor: Welkin Johnson / Endogenous Retroviruses (ERVs) are “fossilized” retroviruses of a once exogenous retrovirus located in the genome of extant vertebrates. Retroviral infection results in a provirus integration into the host genome. An infection of a germline cell could lead to the provirus potentially being inherited by the offspring of the infected individual. Once in the genome, the provirus becomes subject to evolutionary processes and can become either lost or fixed in a population, remaining as “fossils” long after the exogenous retrovirus has gone extinct23. Notably, 8% of the human genome consists of ERVs30. Human Endogenous Retrovirus Type K (HERV-K)(HML-2) family is of particular interest. HERV-K integrations are as old as 30-35 million years, endogenizing before the separation of humans and Old World Monkeys. However, there are human specific insertions, some as young as 150,000 – 250,000 years, making them the youngest insertion in the human genome. There are over 90 insertions in the human genome; the bulk is shared by all humans44,47. Transcripts of HERV-K genes are upregulated in multiple cancer and tumor cell lines 14,39,46, as well as in HIV-1 infected patients 7,11,29. Just as there are human specific insertions of ERV-K, there are also Old World Monkey specific insertions44. I have identified an intact endogenous retroviral envelope open reading frame on chromosome 12 of the rhesus macaque genome. This viral envelope-encoding sequence, which I refer to as rhERV-K env, retains all the canonical features of a retroviral Env protein. An alignment between rhERV-K env and a consensus sequence of HERV-K, HERV-Kcon env, shows a 70% amino acid sequence identity. For experimental purposes, reconstructed HERV-K envelopes have been incorporated into virions of Human Immunodeficiency virus (HIV-1)19,26,49, Murine Leukemia Virus (MLV)12, and Vesicular stomatitis Virus (VSV)26,41,49. While these approaches have illuminated some aspects of HERV-K Env-mediated entry, to date a cell-surface receptor has not been identified for any ERV-K Env. This could be due to its low infectivity levels12,26,49, its seemingly broad cell tropism limiting identification of null cell lines26,49, or possibly the HERV-K consensus reconstructions are not an accurate representation of the progenitor HERV-K virus. I am interested in understanding how the ERV-K retrovirus accessed the human germline (some 150,000 – 250,000 years ago). To do this, I focused specifically on the envelope proteins of HERV-K and rhERV-K, with the goal of analyzing the ERV-K entry process. The identification and inclusion of rhERV-K Env in this study is meant to circumvent the possibility that the previously described consensus reconstructions of human HERV-K Env are not representative, and may also provide a means to compare the endogenization process in the human/ape and old-world monkey lineages. I focused on developing two systems for single-cycle infection, one based on Mason-Pfizer Monkey Virus (MPMV) (which has not been done before), and a second based on MLV, which has previously been reported on. MPMV, like HERV-K, is a betaretrovirus, and I reasoned that possibly using a betaretrovirus would overcome some of the low-infectivity issues associated with prior attempts using HIV and MLV. To develop a system for examining function of the ERV-K Env proteins, I addressed 3 issues: 1. Are the HERV-K Env and rhERV-K Env proteins expressed and properly processed? 2. Can they be incorporated into virions of a heterologous virus? 3. Are ERV-K pseudotyped virions infectious? I have answered these questions in the following thesis. / Thesis (MS) — Boston College, 2017. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Biology.
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Adherence to ART and retention in care among HIV-infected pregnant women starting life-long treatment in Ifakara, Tanzania.Jingo, JohnPaul Kasule January 2014 (has links)
A research report submitted to the faculty of Health Sciences, University of the Witwatersrand in partial fulfillment of the requirements for the Master of Science Degree in Epidemiology. / Antiretroviral therapy (ART) recommendations among HIV – infected pregnant women have been revised several times by the World Health Organization (WHO). Option B+, which is the latest recommendation continues to be rolled out in several countries across the globe but mostly in sub-Saharan Africa. Retention in care and adherence to antiretroviral (ARV) drugs taken by these women remains unclear in this new program. We assessed ability to stay in care (retention) and adherence to ART among HIV – infected women starting life-long treatment during pregnancy and after, at an HIV care and treatment clinic in Ifakara Tanzania. Our study provided an opportunity to understand the trends in adherence to ART and retention in care for this population.
Methods
We analyzed data of HIV-infected pregnant women registered and starting ART for the first time in the Kilombero and Ulanga Antiretroviral Cohort in 2009 and 2010 with a follow up period of up to two years to 2011 and 2012 respectively. Adherence was by patient self-report (PSR) and was sufficient (good) if the woman took all the prescribed pills of the issued batch or insufficient (poor) if she missed two or more pills. Women that missed two or more consecutive scheduled visits to the clinic were not retained while those that honored their scheduled visits were retained in care. Two sample t test and Wilcoxon rank sum test were used to test predictor outcome associations for continuous variables while Pearson’s and Fisher’s exact tests were used for categorical ones. Hazard ratios of each predictor variable were calculated using Cox regression.
Student No: 737395 Page v
Results
A total of 1,282 HIV – infected women were registered in KIULARCO between 2009 and 2010. Fifty (50) were pregnant and started life-long ART upon registration in this period. Of these, 25 (50%) were registered in 2009 and the other 25 (50%) in 2010. Slightly more than half, 52.2% had CD4 cell counts above 350cells/mm3. Almost half, 49% of the women were registered in their final (third) pregnancy trimester. About 82% were in WHO stage one and 60% of all the 50 women were initiated on AZT/3TC/EFV regimen. Only 5.7% had secondary education while the rest had primary or no education at all. Of the women that reported their partners HIV state, 54.5% had partners that had never tested for HIV.
Adherence for all participants was reported as sufficient (good) for the entire period the women were in care. No one had insufficient (poor) adherence. Retention in care was higher during pregnancy than after delivery. Generally, loss to follow up was 40%. About 30% were lost during pregnancy and the majority, 70% lost after they had delivered their babies. There was no evidence to prove that any of the factors studied independently predicted non retention. The most likely time to non retention was six months after delivery.
Conclusions
Our study, despite small sample size, shows that among women diagnosed HIV – infected and starting life-long ART during pregnancy (Option B+), adherence to ART is sufficient and retention in care similar during and after pregnancy. Counseling on the importance of staying in care especially around the first few months after delivery should be emphasized at ANC.
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Prevalência de imagem suspeita de ateroma de carótida em radiografias panorâmicas de pacientes portadores do HIV em tratamento com antirretrovirais / Prevalence of carotid atheroma suspected image in panoramic radiographs of patients with HIV on treatment with antiretroviralsSilva Junior, Newton Guerreiro da 14 June 2013 (has links)
A identificação de ateroma de carótida em radiografia panorâmica de pacientes com alterações sistêmicas que predispõem a aterosclerose é mais frequente do que em amostras da população em geral. O uso da terapia antirretroviral combinada (TARVc), que prolongou a sobrevida dos pacientes portadores do HIV (HIV+), também contribuiu para o aumento da incidência de alterações metabólicas e provavelmente de complicações cardiovasculares. Este estudo teve o objetivo de investigar a prevalência de imagens suspeitas de ateromas de carótida (ISAC) em radiografias panorâmicas de pacientes HIV+ em tratamento no Centro de Atendimento de Pacientes Especiais (CAPE) da Faculdade de Odontologia da Universidade de São Paulo, bem como tentar identificar variáveis associadas à ocorrência destas imagens. Foram avaliadas 300 radiografias de pacientes de ambos os gêneros e com média de idade de 40 anos (18-73 anos). A prevalência de radiografias com ISAC foi de 8,2% (25/300). Estes pacientes apresentaram a média de idade significativamente maior do que a dos pacientes sem ISAC (p= 0,008) e a mediana do nadir de CD4 significativamente menor (p=0,019). O uso do medicamento lopinavir/r (LPV/r) estava associado a chance 2,8 vezes maior para presença de ISAC (OD=2,79 1,12-6,95 IC=95%, p=0,045). Conclui-se que quanto maior a idade maior a probabilidade de ocorrência de ISAC e que as variáveis significativas encontradas (nadir de CD4 e LPV/r) são compatíveis com os fatores de risco cardiovascular observados em pacientes portadores do HIV, relacionados tanto à gravidade da infecção como ao uso de medicamentos. / The identification of calcified carotid artery atheroma (CCAA) in panoramic radiography of patients with systemic diseases that predispose the atherosclerosis is more frequent than in the general population samples. The use of high active antiretroviral therapy (HAART), which prolonged the life of patients with HIV (HIV+), also increase the incidence of cardiovascular complications, probably by the use of protease inhibitors (PI). This study aimed to investigate the prevalence of suspected images of CCAA in panoramic radiographs of HIV+ patients in treatment in the Special Care Dentistry Center of the University of São Paulo, São Paulo, Brazil, as well as trying to identify variables associated with these images. Three hundred radiographs of patients of both genders, with a mean age of 40 years (18-73 years) were evaluated. The prevalence of CCAA suspected images was 8.2% (25/300). This patients showed the mean age significantly higher than that of the patients without CCAA images (p = 0.008) and the CD4 nadir median significantly lower (p = 0.019). The use of HAART with lopinavir/r (LPV/r) was associated with a greater chance for CCAA images (OD 2.79, CI 95% 1.12-6.95; p = 0.045). In conclusion, patients with higher age are more susceptible to CCAA suspected image and the significant variables found (CD4 nadir and LPV/r) are compatible with the cardiovascular risk factors in patients HIV+, related both to the severity of the infection and the use of antiretroviral.
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