Plasma glutamine levels and falciparum malaria

Cowan, Gill M.; Planche, Tim; Agbenyega, Tsiri; Bedu-Addo, George; Owusu-Ofori, Alex; Adebe-Appiah, J.; Agranoff, Dan; Woodrow, Charles J.; Castell, Linda M.; Elford, B C; Krishna, S.

doi:10.1016/s0035-9203(99)90070-6

Cited by 22 publications

(17 citation statements)

References 14 publications

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“…Results presented here extend these previous investigations by demonstrating that children with SMA have significantly lower plasma Gln levels, and that low circulating Gln concentrations are associated with a highly significant increase in the risk of developing severe malaria. Lower levels of circulating Gln have also been reported in Ghanaian children with acute falciparum malaria compared with control cases (81). However, our finding that low levels of Gln in children with malaria are associated with enhanced disease severity appears to differ from a previous finding in Gabonese children with malaria, in which plasma Gln concentrations were higher in children with severe versus moderate disease, and highest in those who died compared with those who survived (82).…”

Section: Discussioncontrasting

confidence: 86%

Reduced Hsp70 and Glutamine in Pediatric Severe Malaria Anemia: Role of hemozoin in Suppressing Hsp70 and NF-κB Activation

Kempaiah

Dokładny

Karim

et al. 2016

Mol Med

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Severe malarial anemia (SMA; hemoglobin [Hb] <5.0 g/dL) is a leading global cause of morbidity and mortality among children residing in Plasmodium falciparum transmission regions. Exploration of molecular pathways through global gene expression profiling revealed that SMA was characterized by decreased HSPA1A, a heat shock protein 70 (Hsp70) coding gene. Hsp70 is a ubiquitous chaperone that regulates nuclear factor-kappa B (NF-κB) signaling and production of proinflammatory cytokines known to be important in malaria pathogenesis (for example, IL-1β, IL-6 and TNF-α). Since the role of host Hsp70 in malaria pathogenesis is unexplored, we investigated Hsp70 and molecular pathways in children with SMA. Validation experiments revealed that leukocytic HSP70 transcripts were reduced in SMA relative to nonsevere malaria, and that intraleukocytic hemozoin (PfHz) was associated with lower HSP70. HSP70 was correlated with reticulocyte production and Hb. Since glutamine (Gln) upregulates Hsp70, modulates NF-κB activation and attenuates overexpression of proinflammatory cytokines, circulating Gln was measured in children with malaria. Reduced Gln was associated with increased risk of developing SMA. Treatment of cultured peripheral blood mononuclear cells (PBMCs) with PfHz caused a time-dependent decrease in Hsp70 transcripts/protein and NF-κB activation. Gln treatment of PBMCs overcame PfHz-induced suppression of HSP70 transcripts/protein, reduced NF-κB activation and suppressed overexpression of IL-1β, IL-6 and TNF-α. These findings demonstrate that SMA is characterized by reduced intraleukocytic HSP70 and circulating Gln, and that PfHz-induced suppression of HSP70 can be reversed by Gln. Thus, Gln supplementation may offer important immunotherapeutic options for futures studies in children with SMA.

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Section: Discussioncontrasting

confidence: 86%

Reduced Hsp70 and Glutamine in Pediatric Severe Malaria Anemia: Role of hemozoin in Suppressing Hsp70 and NF-κB Activation

Kempaiah

Dokładny

Karim

et al. 2016

Mol Med

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“…Creatine is known to decrease in the serum during malaria due to the increase of creatine phosphokinase (CPK) [48]. Reduced glutamine levels in plasma during malaria are associated with sepsis and mortality rate [49]. …”

Section: Resultsmentioning

confidence: 99%

Multivariate modelling with 1H NMR of pleural effusion in murine cerebral malaria

Ghosh

Sengupta

Sharma

et al. 2011

Malar J

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BackgroundCerebral malaria is a clinical manifestation of Plasmodium falciparum infection. Although brain damage is the predominant pathophysiological complication of cerebral malaria (CM), respiratory distress, acute lung injury, hydrothorax/pleural effusion are also observed in several cases. Immunological parameters have been assessed in pleural fluid in murine models; however there are no reports of characterization of metabolites present in pleural effusion.Methods1H NMR of the sera and the pleural effusion of cerebral malaria infected mice were analyzed using principal component analysis, orthogonal partial least square analysis, multiway principal component analysis, and multivariate curve resolution.ResultsIt has been observed that there was 100% occurrence of pleural effusion (PE) in the mice affected with CM, as opposed to those are non-cerebral and succumbing to hyperparasitaemia (NCM/HP). An analysis of 1H NMR and SDS-PAGE profile of PE and serum samples of each of the CM mice exhibited a similar profile in terms of constituents. Multivariate analysis on these two classes of biofluids was performed and significant differences were detected in concentrations of metabolites. Glucose, creatine and glutamine contents were high in the PE and lipids being high in the sera. Multivariate curve resolution between sera and pleural effusion showed that changes in PE co-varied with that of serum in CM mice. The increase of glucose in PE is negatively correlated to the glucose in serum in CM as obtained from the result of multiway principal component analysis.ConclusionsThis study reports for the first time, the characterization of metabolites in pleural effusion formed during murine cerebral malaria. The study indicates that the origin of PE metabolites in murine CM may be the serum. The loss of the components like glucose, glutamine and creatine into the PE may worsen the situation of patients, in conjunction with the enhanced glycolysis, glutaminolysis and increased activity of creatine phophokinase which are already reported characteristic pathophysiological features of malaria.

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“…Moreover, low erythrocyte Gln may contribute to alterations in the erythrocyte redox environment and may play a role in hemolysis and pulmonary hypertension in patients with sickle cell disease [215]. As well, reduced concentrations of plasma Gln have been reported in children with sickle cell disease [216], malaria [217, 218], and β -Thalassemia [219], which may be related to the growth impairment in height and weight also observed in these children.…”

Section: Resultsmentioning

confidence: 99%

Glutamine Supplementation in Sick Children: Is It Beneficial?

Mok

Hankard

2011

Journal of Nutrition and Metabolism

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The purpose of this review is to provide a critical appraisal of the literature on Glutamine (Gln) supplementation in various conditions or illnesses that affect children, from neonates to adolescents. First, a general overview of the proposed mechanisms for the beneficial effects of Gln is provided, and subsequently clinical studies are discussed. Despite safety, studies are conflicting, partly due to different effects of enteral and parenteral Gln supplementation. Further insufficient evidence is available on the benefits of Gln supplementation in pediatric patients. This includes premature infants, infants with gastrointestinal disease, children with Crohn's disease, short bowel syndrome, malnutrition/diarrhea, cancer, severe burns/trauma, Duchenne muscular dystrophy, sickle cell anemia, cystic fibrosis, and type 1 diabetes. Moreover, methodological issues have been noted in some studies. Further mechanistic data is needed along with large randomized controlled trials in select populations of sick children, who may eventually benefit from supplemental Gln.

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Plasma glutamine levels and falciparum malaria

Cited by 22 publications

References 14 publications

Reduced Hsp70 and Glutamine in Pediatric Severe Malaria Anemia: Role of hemozoin in Suppressing Hsp70 and NF-κB Activation

Reduced Hsp70 and Glutamine in Pediatric Severe Malaria Anemia: Role of hemozoin in Suppressing Hsp70 and NF-κB Activation

Multivariate modelling with 1H NMR of pleural effusion in murine cerebral malaria

Glutamine Supplementation in Sick Children: Is It Beneficial?

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