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Tag Archives: Science

Clinical Research and Communities – Conflicting Needs?

The conduct of clinical research often conflicts with community life even if it is done for the benefit of the public. This can be explained by differences in perception, understanding and respective knowledge of each other’s interests and needs. This slide was designed to support discussions around the issues raised by the need to conduct clinical research in communities which often struggle to undertsand the research and how they can impact on what is being done. It can also be used by communities who want to engage with researchers to facilitate the conduct of mutually beneficial clinical research.

HIV Prevention: towards the medicalisation of sex?

2010 will be a year to remember for the field of HIV prevention. After decades of interventions with limited results (with the exception of circumcision and the prevention of mother to child HIV transmission), two clinical studies are raising the hope that the HIV epidemic can be tamed.

In July, the CAPRISA team (based in South Africa) reported that a vaginal gel containing the anti HIV drug tenofovir could reduce the risk of HIV infection by 39%. This was the first proof of concept that a microbicide could potentially reduce the risk of HIV infection whilst offering women an HIV prevention tool that they could control.

In November of the same year, the iPrEx study conducted on a population at high-risk of infection showed that taking the anti HIV Drug Truvada reduced the risk of contracting the virus by an average of 44 percent.

Both studies are hailed as a milestone and landmark in the history of HIV prevention and expectations are high that HIV prevention will finally mean more than the ABC of ‘Abstinence, condom and faithfulness’. But despite the hope, neither approach will immediately translate into marketable products as there are a number of questions that needs answering before microbicide and PrEP are available to the public. Read more »

Postexposure prophylaxis, preexposure prophylaxis or universal test and treat: the strategic use of antiretroviral drugs to prevent HIV acquisition and transmission

Weber, Jonathan; Tatoud, Roger; Fidler, Sarah

AIDS 24 (S4): S27–S39, 2010.

This review considers the use of antiretroviral drugs specifically to prevent HIV transmission. Antiretroviral therapy (ART) can be implemented for the protection of uninfected individuals both before (preexposure prophylaxis) and after (postexposure prophylaxis) exposure to HIV infection. Preexposure prophylaxis may be used coitally dependently when individuals are intermittently exposed or by continuous daily dosing for those constantly exposed; postexposure prophylaxis is used in 28-day courses. Alternatively, ART can be used strategically to reduce the viral load and consequent infectiousness of an HIV-infected individual, thereby limiting the risk of onward viral transmission. A policy of universal HIV testing to enhance the identification of all HIV-positive individuals followed by immediate treatment of all HIV-positive individuals, irrespective of their CD4 cell counts (universal test and treat), has been postulated as a potential tool capable of reducing HIV incidence at a population level. This concept represents a paradigm shift in the use of ART, targeting infectious individuals for prevention rather than protecting uninfected exposed populations. This strategy could have the advantage of preventing transmission and reducing HIV incidence at a population level, as well as delivering universal access to therapy for all people living with HIV and AIDS, potentially eliminating mother-to-child HIV transmission and limiting concomitant diseases such as tuberculosis. This review critically examines the scientific basis of ART for HIV prevention, summarizing the risks and opportunities of the potential expansion of ART for prevention. Specifically, we consider the evidences for and against targeting HIV-uninfected individuals compared with enhanced HIV testing and treatment of HIV-infected individuals in terms of impact on viral transmission.?

Read more or request a reprint

A funding struggle for an HIV prevention in women’s hands

Attendees at the 18th International AIDS conference held in Vienna in July 2010 felt a tremor of hope when Prof. Salim Abdool Karim received a standing ovation following the announcement that a vaginal gel containing the anti-HIV drug tenofovir could reduce the risk of HIV infection by 39%. The groundbreaking results came out of the CAPRISA clinical trial conducted amongst 900 women in rural Vulindela district (KwaZulu-Natal) and urban Durban, South Africa. Euphoria followed in the audience, online and later in the printed media. After 30 years of limited success, the field of HIV prevention could potentially add a new powerful tool to circumcision, condoms, and the prevention of mother to child transmission. Most remarkably, that tool is in women’s hands and the story could unfold with even more good news if it weren’t for a small setback: funding the next clinical studies. Read more »

Scientific Publications

  • Fearnside JF, Dumas ME, Rothwell AR, Wilder SP, Cloarec O, Toye A, Blancher C, Holmes E, Tatoud R, Barton RH, Scott J, Nicholson JK, Gauguier D. Phylometabonomic patterns of adaptation to high fat diet feeding in inbred mice. PLoS ONE 3, e1668 (2008).
  • Toye AA, Dumas ME, Blancher C, Rothwell AR, Fearnside JF, Wilder SP, Bihoreau MT, Cloarec O, Azzouzi I, Young S, Barton RH, Holmes E, McCarthy MI, Tatoud R, Nicholson JK, Scott J, Gauguier D.  Subtle metabolic and liver gene transcriptional changes underlie diet-induced fatty liver susceptibility in insulin-resistant mice. Diabetologia 50, 1867-79 (2007).
  • Daly-Burns B, Alam TN, Mackay A. Clark J, Shepherd CJ, Rizzo S, Tatoud R. O’Hare MJ, Masters JR, Hudson DL. A conditionally immortalized cell line model for the study of human prostatic epithelial cell differentiation. Differentiation 75:35–48, (2007).
  • Dumas ME, Barton RH, Toye A, Cloarec O, Blancher C, Rothwell A, Fearnside A, Tatoud R, Blanc V, Lindon JC, Mitchell SC, Holmes E, McCarthy MI, Scott J, Gauguier J, Nicholson JK. Metabolic profiling reveals a contribution of gut microbiota to fatty liver phenotype in insulin-resistant mice. P.N.A.S. 103:12511–12516, (2006).
  • Arya M, Patel HR, McGurk C, Tatoud R, Klocker H, Masters J, Williamson M. The importance of the CXCL12-CXCR4 chemokine ligand-receptor interaction in prostate cancer metastasis. J Exp Ther Oncol. 4, 291-303 (2004).
  • Stephen RL, Gustafsson MC, Jarvis M, Tatoud R, Marshall BR, Knight D, Ehrenborg E, Harris AL, Wolf CR, Palmer CN. Activation of peroxisome proliferator-activated receptor delta stimulates the proliferation of human breast and prostate cancer cell lines. Cancer Res. 64, 3162-70 (2004)
  • Adamson DJA, Frew D, Tatoud R, Wolf CR & Palmer CNA. Diclofenac antagonizes peroxisome proliferator-activated receptor-? signalling. Mol Pharmacol. 61, 7-12 (2002).
  • Maillard M, Cadot B, Ball RY, Sethia K, Perbal B, Edwards D & Tatoud R. Differential expression of novH proto-oncogene in human prostate cell lines and tissues. Mol Pathol. 54, 275-280 (2001).
  • Tatoud R. Insulin-like growth factor (IGF) network in prostate pathologies. Pr Cancer Pr Dis 2,66-69 (1999).
  • Sangrajrang S, Denoulet P, Millot G, Tatoud R, Podgorniak MP, Tew KD, Calvo F, & Fellous A. Estramustine resistance correlates with tau over-expression in human prostatic carcinoma cells. Int J Cancer 77,626-631 (1998).
  • Sangrajrang S, Denoulet P, Laing NM, Tatoud R, Millot G, Calvo F, Tew KD & Fellous A. Association of estramustine resistance in human prostatic carcinoma cells with modified patterns of tubulin expression. Biochem Pharmacol 55, 325-331 (1998).
  • Le Moyec L, Millot G, Tatoud R, Calvo F & Eugene M. Lipid signals detected by NMR proton spectroscopy of whole cells are not correlated to lipid droplets evidenced by the Nile red staining. Cell Molec Biol 43, 703-709, (1997).
  • deCremoux P, Ravery V, Podgorniak MP, Chevillard S, Toublanc M, Thiounn N, Tatoud R, Delmas V, Calvo F & Boccon-Gibod L. Value of the preoperative detection of prostate-specific-antigen-positive circulating cells by nested RT-PCR in patients submitted to radical prostatectomy. Eur Urol 32, 69-74 (1997).
  • Prévost G, Benamouzig R, Veber N, Fajac A, Tatoud R, Degeorges A. & Eden P. The somatostatin receptor subtype 2 is expressed in normal and tumoral human tissues. Cancer Detection & Prevention 21, 62-70 (1997)
  • Lebbe C, Pellet C, Tatoud R, Agbalika F, Dosquet P, Desgrez JP, Morel P & Calvo F. Absence of human herpesvirus 8 sequences in prostate specimens. AIDS 11, 270 (1997).
  • Lebbé C, Tatoud R, Morel P, Calvo F, Euvrard S, Kanitakis J, Faure M, & Claudy A. Human herpesvirus 8 sequences are not detected in epithelial tumors from patients receiving transplant. Arch Dermatol 133, 111 (1997).
  • Degeorges A, Tatoud R, Fauvel-Lafève F, Podgorniak MP, Millot G, de Cremoux P. & Calvo F. Stromal cells from human benign prostate hyperplasia produce a growth inhibitory factor for LNCaP prostate cancer cells. Int. J. Cancer 68, 207-214 (1996).
  • Le Moyec L, Tatoud R, Degeorges A, Calabresse C, Bauza G, Eugène M. & Calvo F. Multidrug resistance and cellular lipids detected by proton nuclear magnetic resonance spectroscopy in K562 leukemia cell line. Cancer Res 56, 3461-3467 (1996).
  • Tatoud R, Degeorges A, Prévost G, Hoepffner JL, Gauvillé C, Millot G, Thomas F. & Calvo F. Somatostatin receptors in prostate tissues and derived cell cultures, and the in vitro growth inhibitory effect of BIM-23014 analog. Mol Cell Endocrinol 113, 195-204, (1995).
  • Tatoud R, Desgranchamps F, Degeorges A, & Thomas, F. Les facteurs de croissances peptidiques de la prostate. Pathol Biol 41, 731-740, (1993).
  • Le Moyec L, Tatoud R, Eugène M, Gauvillé C, Primot I, Charlemagne D, & Calvo F. Cell and lipid membrane lipid analysis by proton magnetic resonance spectroscopy in five breast cancer cell lines. Br J Cancer 66, 623-628, (1992).
  • Desgranchamps F, Tatoud R, Cussenot O, Teillac P, & Leduc A. Facteurs de croissance prostatiques et hypertrophie bénigne de la prostate. Etat des connaissances actuelles et perspectives. Progres Urol 2, 1031-1044 (1992).
  • Le Moyec L, Eugène M, Gauvillé C, Tatoud R, Ouvrard BN, & Calvo F. Profils lipidiques de lignées de cancer du sein: spectrométrie par résonance magnétique nucléaire du proton. C R Acad Sci Paris, 312(III), 25-30, (1991).

Challenges facing the UK Research Base

The academic year 2007 started with a “Time Bomb” uncovered by the Higher Education Policy Institute (HEPI): student in England are having it the easy way with an average of 26 hours a week spent studying compared to 30 in Ireland, 35 in France and 41 in Portugal. Variations are wide depending on the subject but with less than 15 hours of tuition a week, fears and concerns are raised that Higher Education is going down the drain and will have serious academic consequences for the future of Science in the UK. Read more »

The Reactome

The Reactome project is a collaboration between Cold Spring Harbor Laboratory, The European Bioinformatics Institute, and The Gene Ontology Consortium to develop a curated resource of core pathways and reactions in human biology.

Project Summary: curation of the IRS/PKB cascade of events (6 months).

Role: Supervision and contribution to the work.

The information in the Reactome database is authored by biological researchers with expertise in their fields, maintained by the Reactome editorial staff, and cross-referenced with PubMed, GO, and the sequence databases at NCBI, Ensembl and UniProt. In addition to curated human events, inferred orthologous events in 21 non-human species including mouse, rat, chicken, fugu fish, worms, fly, yeast and E.coli are also available.

This work involved:

  • researching the literature
  • summarising the published knowledge in a synthetic format
  • training and directing the work of a student

The results of this project is now available online to the scientific community.