STUDY DESIGN AND METHODS: Antibody testing results between the years 2013 and 2015 with relevant patient demographic data and red blood cell (RBC) transfusion history were retrieved. Cumulative alloimmunization incidence and evanescence to MUT and Mur were estimated by Kaplan-Meier analysis in relation to the number of RBC units transfused and time.
RESULTS: Of 70,543 selected patients, 6186 nonalloimmunized subjects with available antibody testing results posttransfusion were identified. Cumulative alloimmunization incidence for MUT increased from 0.12% (95% confidence interval [CI], 0.03-0.21) to 0.63% (95% CI, 0.25-1.01), while for Mur it increased from 0.04% (95% CI, 0-0.09) to 0.42% (95% CI, 0.05-0.79) when a patient was transfused 2 RBC units as compared to 12. Both antibodies had high evanescence rates and at 1 year, anti-MUT and -Mur will be detected in only 45% (95% CI, 35%-57%) and 27% (95% CI, 17%-43%), respectively, of previously positive patients. MUT and Mur immunogenicity was estimated to be 1.7 and 1.2 times higher than E when their rate of evanescence was taken into account.
CONCLUSION: Antibodies to MUT and Mur develop following multiple RBC exposures. Immunogenicity of MUT/Mur and evanescence rates of the corresponding antibodies is higher compared to anti-E. Appropriate selection of antibody screening cells is needed in view of the high prevalence, immunogenicity, and evanescence of the antibodies.
AIM OF THE STUDY: To assess the in vitro mutagenicity and in vivo genotoxicity of aqueous extract of V. officinalis leaves using a modified Ames test and rat bone marrow micronucleus assay according to OECD guidelines.
MATERIALS AND METHODS: In vitro Ames test was carried out using different strains of Salmonella (TA97a, TA98, TA100, and TA1535) and Escherichia coli WP2 uvrA (pKM101) in the presence or absence of metabolic activation (S9 mixture). For micronucleus experiment, male and female Sprague-Dawley rats (n = 6/group) were received a single oral daily dose of 500, 1000, and 2000 mg/kg of V. officinalis extract for three days. Negative and positive control rats were received distilled water or a single intraperitoneal injection of 50 mg/kg of cyclophosphamide, respectively. Following dissection, femurs were collected and bone marrow cells were stained with May-Grünwald-Giemsa solution for micronucleus assessment.
RESULTS: Ames test results demonstrated that 5, 2.5, 1.25 and 0.625 mg/ml of V. officinalis extract induced a significant mutagenic effect against TA100 and TA98 strains (with and without metabolic activation). Findings of the animal study showed there were no significant increase in the micronucleated polychromatic erythrocytes (MNPE) and no significant alterations in the polychromatic erythrocytes (PCE) to normochromatic erythrocytes (NCE) ratio of treated rats as compared with their negative control. Meanwhile, significantly increased in the MNPEs was seen in the cyclophosphamide-treated group only.
CONCLUSION: Aqueous extract of V. officinalis has mutagenic effect against TA98 and TA100 strains as demonstrated by Ames test, however, there is no in vivo clastogenic and myelotoxic effect on bone marrow micronucleus of rats indicating that the benefits of using V. officinalis in traditional practice should outweigh risks.
METHODS: The expression of CRP CR1, CD55, CD59, and the phagocytic regulator CD47, on uninfected normocytes and reticulocytes were assessed in individuals from two study populations: (1) P. falciparum and P. vivax-infected patients from a low transmission setting in Sabah, Malaysia; and, (2) malaria-naïve volunteers undergoing P. falciparum induced blood-stage malaria (IBSM). For clinical infections, individuals were categorized into anaemia severity categories based on haemoglobin levels. For IBSM, associations between CRPs and haemoglobin level were investigated.
RESULTS: CRP expression on RBC was lower in Malaysian individuals with P. falciparum and P. vivax mild malarial anaemia compared to healthy controls. CRP expression was also reduced on RBCs from volunteers during IBSM. Reduction occurred on normocytes and reticulocytes. However, there was no significant association between reduced CRPs and haemoglobin during IBSM.
CONCLUSIONS: Removal of CRPs occurs on both RBCs and reticulocytes during Plasmodium infection even in mild malarial anaemia and at low levels of parasitaemia.