Browsing by Subject "Hypoxia"

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    Open Access
    Hypoxia induces an immunodominant target of tuberculosis specific T cells absent from common BCG vaccines
    (Public Library of Science, 2010) Gideon, Hannah Priyadarshini; Wilkinson, Katalin Andrea; Rustad, Tige R; Oni, Tolu; Guio, Heinner; Kozak, Robert Andrew; Sherman, David R; Meintjes, Graeme; Behr, Marcel A; Vordermeier, Hans Martin
    Author Summary Mycobacterium tuberculosis (the cause of tuberculosis) can persist for many years in humans without causing disease but has the potential to reactivate. One of the conditions the bacterium must survive in these circumstances is hypoxia. In order to do so, the bacterium uses a characteristic set of genes that help alter its metabolism. It follows that the products of such genes may encode protein antigens that can be recognized by the immune response. We therefore analyzed gene response patterns of tuberculosis subject to prolonged hypoxia as a guide to the discovery of new antigens that might be useful as vaccines or diagnostic agents. Amongst the genes most strongly increased by low oxygen levels, one was identified (known as Rv1986) that is missing from most strains of the tuberculosis vaccine Mycobacterium bovis BCG. When we analyzed human immune responses to this protein in tuberculosis infected people our experiments showed it was particularly well recognized by cells that produce a chemical messenger (cytokine) called interleukin-2. Interleukin-2 is important for long-term immunological memory. The BCG vaccine is only partially effective and our experiments therefore suggest one of the reasons could be that an important immunological target is missing from many strains. Further evaluation of BCG strains in which Rv1986 is present or absent is therefore warranted in the hope that this might improve the efficacy of existing or new tuberculosis vaccines.
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    Open Access
    Improving Reconstituted HDL Composition for Efficient Post-Ischemic Reduction of Ischemia Reperfusion Injury
    (Public Library of Science, 2015) Brulhart-Meynet, Marie-Claude; Braunersreuther, Vincent; Brinck, Jonas; Montecucco, Fabrizio; Prost, Jean-Christophe; Thomas, Aurelien; Galan, Katia; Pelli, Graziano; Pedretti, Sarah; Vuilleumier, Nicolas
    BACKGROUND: New evidence shows that high density lipoproteins (HDL) have protective effects beyond their role in reverse cholesterol transport. Reconstituted HDL (rHDL) offer an attractive means of clinically exploiting these novel effects including cardioprotection against ischemia reperfusion injury (IRI). However, basic rHDL composition is limited to apolipoprotein AI (apoAI) and phospholipids; addition of bioactive compound may enhance its beneficial effects. Objective The aim of this study was to investigate the role of rHDL in post-ischemic model, and to analyze the potential impact of sphingosine-1-phosphate (S1P) in rHDL formulations. Methods and RESULTS: The impact of HDL on IRI was investigated using complementary in vivo , ex vivo and in vitro IRI models. Acute post-ischemic treatment with native HDL significantly reduced infarct size and cell death in the ex vivo , isolated heart (Langendorff) model and the in vivo model (-48%, p<0.01). Treatment with rHDL of basic formulation (apoAI + phospholipids) had a non-significant impact on cell death in vitro and on the infarct size ex vivo and in vivo . In contrast, rHDL containing S1P had a highly significant, protective influence ex vivo , and in vivo (-50%, p<0.01). This impact was comparable with the effects observed with native HDL. Pro-survival signaling proteins, Akt, STAT3 and ERK1/2 were similarly activated by HDL and rHDL containing S1P both in vitro (isolated cardiomyocytes) and in vivo . CONCLUSION: HDL afford protection against IRI in a clinically relevant model (post-ischemia). rHDL is significantly protective if supplemented with S1P. The protective impact of HDL appears to target directly the cardiomyocyte.
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    The prevalence of hypotension and hypoxaemia in blunt traumatic brain injury in the prehospital setting of Johannesburg, South Africa: A retrospective chart review
    (2014) Stassen, W; Welzel, T
    BACKGROUND: Each year, ~89 000 (180/100 000) new cases of head injury are reported in South Africa (SA), with the majority of patients being in the economically active population. Hypotension and hypoxaemia significantly increase the morbidity and mortality in patients who have suffered a traumatic brain injury (TBI). Cerebral tissue is particularly vulnerable to these secondary insults in the period immediately following a TBI, emphasising the importance of prehospital care in TBI. OBJECTIVE: To establish the prevalence of prehospital hypotension and hypoxaemia in moderate to severe blunt TBI in greater Johannesburg, Gauteng, SA. METHODS: The records of adult patients who sustained a moderate to severe TBI between 1 January and 31 December 2011 were retrospectively reviewed for hypotension (systolic blood pressure <90 mmHg) and hypoxaemia (oxygen saturation <90%) during their prehospital phase of care. These results were subject to descriptive analysis. RESULTS: A total of 299 records were identified, 66 of which met the inclusion criteria. The prevalence of prehospital hypotension and hypoxaemia were 33.3% (n=22) and 37.9% (n=25), respectively, while 21.2% (n=14) of patients suffered double insults of hypotension and hypoxaemia. Hypotension and hypoxaemia were associated with haemorrhage (p=0.011) and chest injuries (p=0.001), respectively. CONCLUSION: The prevalence of hypotension in this study was similar to that observed in international studies, but the prevalence of hypoxaemia was much higher. There is a need for local guidelines to be developed to inform the quality of TBI care in the context of the developing world.