A comparison of washed and volume‐reduced platelets with respect to platelet activation,aggregation, and plasma protein removal

BACKGROUND: Washed or volume‐reduced platelets (PLTs) are occasionally requested for patients with a history of allergic or anaphylactic transfusion reactions. However, conclusive data are not available as to which method is more suitable. STUDY DESIGN AND METHODS: A direct comparison of saline‐washed and volume‐reduced PLTs was performed by splitting 11 units of 6‐day‐old apheresis PLT units. PLT activation, aggregation, plasma protein, and PLT count were determined before and after each procedure. To assess whether washing using neutral, calcium‐free Ringer's acetate (NRA) would better preserve PLT function, 8 additional units of apheresis PLTs were split and were washed in saline or NRA. RESULTS: Saline washing resulted in significantly increased number of activated, P‐selectin–expressing PLTs compared to volume reduction (24.2% vs. 10.3%, p = 0.001). Aggregation was also significantly reduced (?40.6% vs. ?0.8%, p = 0.004). Plasma protein removal was significantly better for saline‐washed than volume‐reduced PLTs (96% vs. 51.1%, p < 0.001). PLT recovery was not significantly different for saline‐washed versus volume‐reduced PLTs (70.5% vs. 80.7%, p = 0.079). There was no difference between washing in saline or NRA with regard to PLT activation and loss of aggregation. CONCLUSIONS: PLT washing with saline or NRA significantly increases PLT activation and decreases PLT aggregability. On the other hand, volume reduction does not adequately remove plasma proteins. Therefore, PLT washing should be reserved for patients with a history of severe allergic or anaphylactic transfusion reactions. We suggest that fresher PLTs be selected to improve the functionality of washed PLTs.     

Concentration of the macrolide antibiotic tulathromycin in broncho-alveolar cells is influenced by comedication of rifampicin in foals

Macrolide antibiotics penetrate in the lung against steep concentration gradients into the epithelial lining fluid (ELF) and broncho-alveolar cells (BAC). Since they interact with ABCB1, ABCC2, and organic anion transporting proteins (OATPs), which are localized to lung tissue, pulmonary concentration may be influenced by rifampicin (RIF), an inducer and modulator of efflux and uptake transporters. We measured concentrations of tulathromycin (TM) in plasma, ELF and BAC in 21 warm-blooded foals 24 and 192 h after first and last intramuscular injection of 2.5 mg/kg TM once weekly for 6 weeks. In 11 foals, TM was combined with RIF (10 mg/kg twice daily), and mRNA expression of ABCB1 and ABCC2 in BAC was assessed before and after RIF. Affinity of TM to ABCB1 and ABCC2 was measured by transport assays using cell monolayers and membrane vesicles of MDCKII and 2008 cells transfected with ABCB1 and ABCC2, respectively. At steady state, TM concentrated manifold in ELF and BAC. Comedication of RIF significantly decreased the AUC of TM (18.5?±?4.0 versus 24.4?±?3.7 µg?×?h/ml, p?<?0.05) and lowered its concentrations in plasma (24 h, 0.17?±?0.05 versus 0.24?±?0.05 µg/ml; 192 h, 0.05?±?0.01 versus 0.06?±?0.01 µg/ml) and BAC (24 h, 0.84?±?0.36 versus 1.56?±?1.02 µg/ml; 192 h, 0.60?±?0.23 versus 1.23?±?0.90 µg/ml, all p?<?0.05). Treatment with rifampicin did not markedly induce ABCB1 and ABCC2 expression. TM had no affinity to ABCB1 and ABCC2 in vitro. Concentration of TM in the lung of foals was significantly lowered by comedication of rifampicin most likely caused by extrapulmonary mechanisms leading to lower plasma concentrations.     

Alleviation of IgM monoclonal protein interference in nephelometric assays by sample treatment with reducing agent in a chaotropic salt solution

In some patients, the presence of monoclonal IgM proteins can cause substantial false elevation in nephelometric assays. A 59-year-old woman with previously unrecognized Waldenstr?m macroglobulinemia had high serum viscosity. Nephelometric analysis revealed elevated measured concentrations of IgG, IgA, and IgM. Pretreatment with a reducing salt solution yielded resolution of cross-linked immunoglobulins into a distinct IgM κ monoclonal protein band by immunofixation electrophoresis. Measured quantitative immunoglobulin measurements in treated and untreated specimens were compared. An approximately 50% drop in IgG and IgA concentrations was observed in the presence of reducing agent, while IgM concentrations were unchanged. We report that the addition of reducing agent solution can alleviate artifactual elevation of nephelometric determination of IgG and IgA concentrations. These results are consistent with dissociation of higher order IgM complexes, leading to reduction of nonspecific light scattering by IgM complexes in IgA and IgG nephelometric reactions.     

Therapeutic Efficacy of the N,N′ Bis-(2-Mercaptoethyl) Isophthalamide Chelator for Methylmercury Intoxication in Caenorhabditis elegans

Neurotoxicity Research - Methylmercury (MeHg) is a global pollutant and potent neurotoxin. In humans, MeHg damages the central nervous system (CNS), causing irreversible neuronal shrinkage, and...