Prostaglandins are known to be produced by macrophages when challenged with Trypanosoma cruzi, the etiological agent of Chagas' disease. It is not known whether these lipid mediators play a role in oxidative stress in host defenses against this important protozoan parasite. In this study, we demonstrated that inducible cyclooxygenase-mediated prostaglandin production is a key chemical mediator in the control of parasite burden and erythrocyte oxidative stress during T. cruzi infection in C57BL/6 and BALB/c mice, prototype hosts for the study of resistance and susceptibility in murine Chagas' disease. The results suggested the existence of at least two mechanisms of oxidative stress, dependent or independent with regard to the nitric oxide and cyclooxygenase pathway, where one or the other is more evident depending on the mouse strain.
Chagas' disease is accompanied by severe anemia and oxidative stress, which may contribute to mortality. In this study, we investigated the role of 5-lipoxygenase (5-LO) in the control of parasitism and anemia associated with oxidative damage of erythrocytes in experimental Trypanosoma cruzi infection. Wild-type C57BL/6, 129Sv mice treated or not with nordihydroguaiaretic acid (NDGA, 5-LO inhibitor), mice lacking the 5-LO enzyme gene (5-LO(-/-)) and inducible nitric oxide synthase gene (iNOS(-/-)) were infected with the Y strain of T. cruzi. Impairment of 5-LO resulted in increased numbers of trypomastigote forms in the blood and amastigote forms in the heart of infected mice. We assessed oxidative stress in erythrocytes by measuring oxygen uptake, induction time and chemiluminescence following treatment with tert-butyl hydroperoxide (TBH). Our results show that 5-LO metabolites increased lipid peroxidation levels in erythrocytes during the early phase of murine T. cruzi infection. NDGA treatment reduced oxidative damage of erythrocytes in C57BL/6 T. cruzi-infected mice but not in C57BL/6 iNOS(-/-) infected mice, showing that the action of NDGA is dependent on endogenous nitric oxide (NO). In addition, our results show that 5-LO metabolites do not participate directly in the development of anemia in infected mice. We conclude that 5-LO products may not only play a major role in controlling heart tissue parasitism, i.e., host resistance to acute infection with T. cruziin vivo, but in the event of an infection also play an important part in erythrocyte oxidative stress, an NO-dependent effect.
The aim of this study is to determinate the prevalence of oropharyngeal colonization by group A beta-hemolytic Streptococcus (GABHS) in pediatric population of Ponta Grossa, a midsize city of southern Brazil; estimate the effectiveness of antistreptolysin-O (ASO), compared to culture, in presence of infection; and design an unpublished investigative algorithm of rheumatic fever's suspicion, based on needs identified in worldwide consensus. It is an epidemiologic, observational and transversal study, involving 180 children younger than 12 years. Secretion of posterior oropharynx was collected for culture; and peripheral blood for determination of ASO. Student-t and chi-square tests, with Yates correction, were performed for statistical analysis. The ASO cutoff was determined by Receiver Operating Characteristic (ROC) curve. The prevalence encountered was 3.9%, and 25.5% of the children showed reagent ASO. This serological test demonstrated quantitatively and qualitatively significant associations to the GABHS presence (p=0.0001 for both associations) throughout the ROC curve, 200 U Todd was the value that resulted in the best accuracy, demonstrating 100% of sensibility and 80% of specificity in the GAS infection documentation. Also, it was found that the value of 1.200 U represents a specificity of 100%. The results emphasize the need for similar studies in other populations, to provide better targeting of the diagnosis and treatment of oropharyngitis by GABHS, which in turn can prevent up to 80% the cases of rheumatic fever, and consequently, the chronic rheumatic heart disease.
The estimated glomerular filtration rate is a rather important measurement for patients under intensive care, since they often receive several drugs, and impaired renal function may result in misleading dosing. The estimated glomerular filtration is derived from mathematical models using serum creatinine, a measurement that suffers interference of some drugs, such as metamizole. The study intented to evaluate the impact on patient stratification for dose adjustment of two antimicrobials (meropenem and vancomycin) caused by metamizole interference in creatinine measurement by dry chemistry. A cross-sectional study was conducted with a group of 108 hospitalized patients under metamizole prescriptions at fixed intervals. Serum creatinine levels were determined by enzymatic dry chemistry and Jaffé assays and the estimated glomerular filtration rate was calculated through the CKD-EPI equation. Patients were stratified in groups according to their estimated glomerular filtration rate for drug dosing of vancomycin and meropenem. As expected, creatinine values were significantly lower in measurements performed by the dry chemistry method in comparison to Jaffé assay (p<0.0001) when patients are under metamizole treatment. A significant bias (-40.3%) was observed between those two methods, leading to a significant difference (p<0.0001) in patient classification according to renal function using the CKD-EPI equation for dosing adjustment. Thus, during the validity of metamizole treatment, the stratification for drug dosing by the estimated glomerular filtration rate is not reliable if the creatinine measurement is done through dry chemistry. Clinical and laboratory staff must be aware of these limitations and cooperate to optimize pharmacotherapy.
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