115 research outputs found

    Absence of <i>Pneumocystis jirovecii</i> colonization in human immunodeficiency virus-infected individuals with and without airway obstruction and with undetectable viral load

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    Pneumocystis jirovecii colonization has been associated with non-acquired immune deficiency syndrome (AIDS) pulmonary comorbidity. We used spirometry to measure pulmonary function and analyzed oral wash specimens by quantitative polymerase chain reaction (PCR), targeting the large mitochondrial ribosomal subunit. For sensitivity control, a blinded subsample was subjected to touch-down PCRs, targeting both large and small ribosomal subunits and the major surface glycoprotein. Pneumocystis jirovecii deoxyribonucleic acid (DNA) was detected in 1 of 156 (95% confidence interval, .1%–3.5%) virologically suppressed human immunodeficiency virus (HIV)-infected individuals confirmed by all PCR methods. Thus, prevalence of P jirovecii colonization was low and unlikely to be a major cause of pulmonary comorbidity in this group of well treated HIV-infected individuals

    Systemic and cerebral vascular endothelial growth factor levels increase in murine cerebral malaria along with increased Calpain and caspase activity and can be reduced by erythropoietin treatment

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    The pathogenesis of cerebral malaria (CM) includes compromised microvascular perfusion, increased inflammation, cytoadhesion, and endothelial activation. These events cause blood–brain barrier disruption and neuropathology and associations with the vascular endothelial growth factor (VEGF) signaling pathway have been shown. We studied this pathway in mice infected with Plasmodium berghei ANKA causing murine CM with or without the use of erythropoietin (EPO) as adjunct therapy. ELISA and western blotting was used for quantification of VEGF and relevant proteins in brain and plasma. CM increased levels of VEGF in brain and plasma and decreased plasma levels of soluble VEGF receptor 2. EPO treatment normalized VEGF receptor 2 levels and reduced brain VEGF levels. Hypoxia-inducible factor (HIF)-1α was significantly upregulated whereas cerebral HIF-2α and EPO levels remained unchanged. Furthermore, we noticed increased caspase-3 and calpain activity in terminally ill mice, as measured by protease-specific cleavage of α-spectrin and p35. In conclusion, we detected increased cerebral and systemic VEGF as well as HIF-1α, which in the brain were reduced to normal in EPO-treated mice. Also caspase and calpain activity was reduced markedly in EPO-treated mice

    Glucagon-like peptide-1 analogue, liraglutide, in experimental cerebral malaria: implications for the role of oxidative stress in cerebral malaria

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    BACKGROUND: Cerebral malaria from Plasmodium falciparum infection is major cause of death in the tropics. The pathogenesis of the disease is complex and the contribution of reactive oxygen and nitrogen species (ROS/RNS) in the brain is incompletely understood. Insulinotropic glucagon-like peptide-1 (GLP-1) mimetics have potent neuroprotective effects in animal models of neuropathology associated with ROS/RNS dysfunction. This study investigates the effect of the GLP-1 analogue, liraglutide against the clinical outcome of experimental cerebral malaria (ECM) and Plasmodium falciparum growth. Furthermore the role of oxidative stress on ECM pathogenesis is evaluated. METHODS: ECM was induced in Plasmodium berghei ANKA-infected C57Bl/6j mice. Infected Balb/c (non-cerebral malaria) and uninfected C57Bl/6j mice were included as controls. Mice were treated twice-daily with vehicle or liraglutide (200 μg/kg). ROS/RNS were quantified with in vivo imaging and further analyzed ex vivo. Brains were assayed for cAMP, activation of cAMP response element binding protein (CREB) and nitrate/nitrite. Plasmodium falciparum was cultivated in vitro with increasing doses of liraglutide and growth and metabolism were quantified. RESULTS: The development and progression of ECM was not affected by liraglutide. Indeed, although ROS/RNS were increased in peripheral organs, ROS/RNS generation was not present in the brain. Interestingly, CREB was activated in the ECM brain and may protect against ROS/RNS stress. Parasite growth was not adversely affected by liraglutide in mice or in P. falciparum cultures indicating safety should not be a concern in type-II diabetics in endemic regions. CONCLUSIONS: Despite the breadth of models where GLP-1 is neuroprotective, ECM was not affected by liraglutide providing important insight into the pathogenesis of ECM. Furthermore, ECM does not induce excess ROS/RNS in the brain potentially associated with activation of the CREB system

    Prolonged and persistent diarrhoea is not restricted to children with acute malnutrition:An observational study in Ethiopia

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    Under embargo until: 2020-07-20Objectives: To assess the prevalence of prolonged and persistent diarrhoea, to estimate their co‐occurrence with acute malnutrition and association with demographic and clinical factors. Methods: Case–control study where cases were children under 5 years of age with diarrhoea and controls were children without diarrhoea, frequency‐matched weekly by age and district of residency. Controls for cases 0–11 months were recruited from vaccination rooms, and controls for cases 12–59 months were recruited by house visits using random locations in the catchment area of the study sites. Data were analysed by mixed model logistic regression. Results: We enrolled 1134 cases and 946 controls. Among the cases, 967 (85%) had acute diarrhoea (AD), 129 (11%) had ProD and 36 (3.2%) had PD. More cases had acute malnutrition at enrolment (17% vs. 4%, P < 0.0001) and more were born prematurely (5.7% vs. 1.8%, P < 0.0001) than controls. About 75% of ProPD cases did not have acute malnutrition. Cases with AD and ProPD had different symptomatology, even beyond illness duration. Conclusions: ProPD is common among children presenting with diarrhoea and is not confined to children with acute malnutrition. There is an urgent need for studies assessing causes of ProPD with and without acute malnutrition to develop treatment guidelines for these conditions.acceptedVersio
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