Home About us Contact
|
Home About us Contact | ||
|
|
||
Macaque Model (macaque + model)
Selected AbstractsMacaques co-immunized with SIVgag/pol-HIVenv and IL-12 plasmid have increased cellular responsesJOURNAL OF MEDICAL PRIMATOLOGY, Issue 4-5 2007T.M. Robinson Abstract Background, The cell mediated immune profiles following immunization with a recombinant DNA vaccine was assessed in the simian-human immunodeficiency virus (SHIV) and Macaque model. Earlier work demonstrated increased numbers of antigen specific CD8 and CD4 effector cells able to secrete IFN- ,. Method, The vaccine strategy included co-immunization of a DNA based vaccine alone or in combination with a macaque IL-12 expressing plasmid (pmacIL12). Antigen activated lymphocytes were studied for activation of a set of immunological molecules. Results, The current study demonstrates lymphocytes isolated and activated from the group that was immunized with DNA and pmacIL12 had a higher level of IFN- , producing cells. We also observed a different immunological profile when comparing the cells isolated from macaques immunized with DNA as compared to those animals that also received pmacIL12. Conclusion, The observed immune profiles are reflective of the co-delivery of pmacIL12 and demonstrates that IL-12 can increase the magnitude and polyfunctionality of the cellular immune response. [source] Tenofovir disoproxil fumarate in pregnancy and prevention of mother-to-child transmission of HIV-1: is it time to move on from zidovudine?HIV MEDICINE, Issue 7 2009C Foster Objectives Zidovudine (ZDV) has been the cornerstone of antiretroviral (ARV) therapy for pregnant women infected with HIV-1 in the prevention of mother-to-child transmission (MTCT) and remains the only licensed ARV for use in pregnancy. We explored the current and future roles of tenofovir disoproxil fumarate (TDF) in the prevention of MTCT of HIV-1. Methods We reviewed the published literature by conducting database searches of in vitro, animal and clinical studies, reported in journals and at conferences, using the search terms Tenofovir/gs4331/viread, pregnant/pregnancy, lactate, lactation, natal, reproduce/reproduction, placenta/placental, malformation, and teratogenicity/teratogenic. Results In a macaque model, perinatal exposure to very high dose tenofovir resulted in bone toxicity in some offspring. However, perinatal use of TDF, both single dose and as part of highly active antiretroviral therapy in women, has been well tolerated in the short term by mothers and their infants. Further, the addition of single-dose TDF to single-dose nevirapine (SD-NVP) during delivery following maternal ZDV use during pregnancy significantly reduces the frequency of nonnucleoside reverse transcriptase inhibitor (NNRTI) resistance. Conclusions The addition of TDF to SD-NVP reduces NNRTI resistance. The role of TDF in this setting and during pregnancy for reducing rates of MTCT requires investigation. While short-term toxicity data are encouraging, long-term follow-up of exposed mothers and infants is required. [source] Gene expression profiling of gut mucosa and mesenteric lymph nodes in simian immunodeficiency virus-infected macaques with divergent disease courseJOURNAL OF MEDICAL PRIMATOLOGY, Issue 4-5 2006M.D. George Abstract Background, Although the majority of drug-naïve HIV-infected patients develop acquired immunodeficiency syndrome (AIDS), a small percentage remains asymptomatic without therapeutic intervention. Methods, We have utilized the simian immunodeficiency virus (SIV)-infected rhesus macaque model to gain insights into the molecular mechanisms of long-term protection against simian AIDS. Results, Chronically SIV-infected macaques with disease progression had high viral loads and CD4+ T-cell depletion in mucosal tissue and peripheral blood. These animals displayed pathologic changes in gut-associated lymphoid tissue (GALT) and mesenteric lymph node that coincided with increased expression of genes associated with interferon induction, inflammation and immune activation. In contrast, the animal with long-term asymptomatic infection suppressed viral replication and maintained CD4+ T cells in both GALT and peripheral blood while decreasing expression of genes involved in inflammation and immune activation. Conclusions, Our findings suggest that reduced immune activation and effective repair and regeneration of mucosal tissues correlate with long-term survival in SIV-infected macaques. [source] Chronic immune stimulation accelerates SIV-induced disease progressionJOURNAL OF MEDICAL PRIMATOLOGY, Issue 5 2001François Villinger The contribution of chronic immune stimulation on the progression of lentivirus-induced disease was evaluated in the SIVmac251 macaque model of AIDS. Following SIV inoculation, seroconversion and control of the acute viral replication phase, repeated immune stimulations with tetanus toxoid (TT), keyhole limpet hemocyanin (KLH) and allogeneic peripheral blood mononuclear cells (PBMC) were initiated in four monkeys. These animals showed a significant shortening of survival when compared with eight non-immune-stimulated control animals inoculated with the same route, dose and stock of SIVmac251 (median survival 9.5 months versus 17 months, P=0.010). In addition, when the comparison was extended to another 22 control animals of different origin but inoculated by the same route with similar doses and stocks of SIVmac251, the difference in survival was still significant (9.5 versus 18 months, P=0.003). This accelerated progression of symptomatic disease was not accompanied with significant increases in plasma viral loads, but suboptimal antibody responses to the immunizing antigens were noted, correlating with the length of survival. These findings may have implications for HIV-infected humans suffering from chronic infectious diseases. [source] Tumor necrosis factor neutralization results in disseminated disease in acute and latent Mycobacterium tuberculosis infection with normal granuloma structure in a cynomolgus macaque modelARTHRITIS & RHEUMATISM, Issue 2 2010Philana Ling Lin Objective An increased risk of tuberculosis has been documented in humans treated with tumor necrosis factor , (TNF,),neutralizing agents. In murine models, impaired signaling by TNF causes exacerbation of both acute and chronic infection associated with aberrant granuloma formation and maintenance. This study was undertaken to investigate immune modulation in the setting of TNF neutralization in primary and latent tuberculosis in a non-human primate model. Methods Cynomolgus macaques 4 years of age or older were infected with Mycobacterium tuberculosis and subjected to clinical, microbiologic, immunologic, and radiographic examinations. Monkeys were classified as having active or latent disease 6,8 months after infection, based on clinical criteria. Monkeys used in acute infection studies were randomized to receive either adalimumab (prior to and during infection) or no treatment. Monkeys with latent infection that were randomized to receive TNF-neutralizing agent were given either an inhibitor of soluble TNF, recombinant methionyl human soluble TNF receptor I (p55-TNFRI), or adalimumab. Control monkeys with latent infection were given no treatment or saline. Data from previously studied monkeys with active or latent disease were also used for comparison. Results Administration of TNF-neutralizing agents prior to M tuberculosis infection resulted in fulminant and disseminated disease by 8 weeks after infection. Neutralization of TNF in latently infected cynomolgus macaques caused reactivation in a majority of animals as determined by gross pathologic examination and bacterial burden. A spectrum of dissemination was noted, including extrapulmonary disease. Surprisingly, monkeys that developed primary and reactivation tuberculosis after TNF neutralization had similar granuloma structure and composition to that of control monkeys with active disease. TNF neutralization was associated with increased levels of interleukin-12, decreased levels of CCL4, increased chemokine receptor expression, and reduced mycobacteria-induced interferon-, production in blood but not in the affected mediastinal lymph nodes. Finally, the first signs of reactivation often occurred in thoracic lymph nodes. Conclusion These findings have important clinical implications for determining the mechanism of TNF neutralization,related tuberculosis. [source] Salvaging The Ischaemic Penumbra: More Than Just Reperfusion?CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 1-2 2002Thanh G Phan SUMMARY 1. The ischaemic penumbra is defined as a moderately hypoperfused region that retains structural integrity but has lost function. In animal models of ischaemic stroke, this region is prone to recurrent anoxic depolarization and will become infarcted if reperfusion does not occur. In the macaque model, an ischaemic penumbra has been identified for up to 3 h after ischaemic stroke onset, whereas in selected human patients it may exist for up to 48 h. 2. Although most definitions of the ischaemic penumbra stress a ,time,brain volume' concept, few incorporate the idea that selective and delayed neuronal injury plays an important role. Thus, in addition to necrotic cell death caused by acute injury, it is important to also consider delayed death mediated by caspase-dependent and -independent apoptotic pathways. 3. ,Salvage' of penumbral tissue is possible if reperfusion (e.g. after thrombolysis) occurs. However, neurons within this ,salvaged' region may be still at risk of further delayed neuronal injury. 4. In the present review, we aim to revisit the concept of the ischaemic penumbra and explore the role of selective and delayed neuronal injury in enlargement of the volume of infarction, as well as pathogenic mechanisms of white matter ischaemia. Both animal and human models of cerebral ischaemia imaged using magnetic resonance and positron emission tomography techniques will be discussed. [source] | ||||||||||